﻿FN Clarivate Analytics Web of Science
VR 1.0
PT J
AU Linetsky, M
   Bondelid, KS
   Losovskiy, S
   Gabyak, V
   Rullo, MJ
   Stiadle, TI
   Munjapara, V
   Saxena, P
   Ma, DM
   Cheng, YS
   Howes, AM
   Udeigwe, E
   Salomon, RG
AF Linetsky, Mikhail
   Bondelid, Karina S.
   Losovskiy, Sofiya
   Gabyak, Vadym
   Rullo, Mario J.
   Stiadle, Thomas I.
   Munjapara, Vasu
   Saxena, Priyali
   Ma, Duoming
   Cheng, Yu-Shiuan
   Howes, Andrew M.
   Udeigwe, Emeka
   Salomon, Robert G.
TI 4-Hydroxy-7-oxo-5-heptenoic Acid Lactone Is a Potent Inducer of the
   Complement Pathway in Human Retinal Pigmented Epithelial Cells
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; ALTERNATIVE-PATHWAY; OXIDATIVE STRESS;
   CIGARETTE-SMOKE; C-3 CONVERTASE; SODIUM IODATE; HOHA LACTONE; FACTOR-B;
   ACTIVATION; DRUSEN
AB We previously discovered that oxidative cleavage of docosahexaenoate (DHA), which is especially abundant in the retinal photoreceptor rod outer segments and retinal pigmented endothelial (RPE) cells, generates 4-hydroxy-7-oxo-5-heptenoate (HOHA) lactone, and that HOHA lactone can enter RPE cells that metabolize it through conjugation with glutathione (GSH). The consequent depletion of GSH results in oxidative stress. We now find that HOHA lactone induces upregulation of the antioxidant transcription factor Nrf2 in ARPE-19 cells. This leads to expression of GCLM, HO1, and NQO1, three known Nrf2-responsive antioxidant genes. Besides this protective response, HOHA lactone also triggers a countervailing inflammatory activation of innate immunity. Evidence for a contribution of the complement pathway to age-related macular degeneration (AMD) pathology includes the presence of complement proteins in drusen and Bruch's membrane from AMD donor eyes, and the identification of genetic susceptibility loci for AMD in the complement pathway. In eye tissues from a mouse model of AMD, accumulation of complement protein in Bruch's membrane below the RPE suggested that the complement pathway targets this interface, where lesions occur in the RPE and photoreceptor rod outer segments. In animal models of AMD, intravenous injection of NaIO3 to induce oxidative injury selectively destroys the RPE and causes secretion of factor C3 from the RPE into areas directly adjacent to sites of RPE damage. However, a molecular-level link between oxidative injury and complement activation remained elusive. We now find that sub-micromolar concentrations of HOHA lactone foster expression of C3, CFB, and C5 in ARPE-19 cells and induce a countervailing upregulation of CD55, an inhibitor of C3 convertase production and complement cascade amplification. Ultimately, HOHA lactone causes membrane attack complex formation on the plasma membrane. Thus, HOHA lactone provides a molecular-level connection between free-radical-induced oxidative cleavage of DHA and activation of the complement pathway in AMD pathology.
C1 [Linetsky, Mikhail; Stiadle, Thomas I.; Ma, Duoming; Cheng, Yu-Shiuan; Udeigwe, Emeka; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
   [Bondelid, Karina S.; Rullo, Mario J.; Munjapara, Vasu; Saxena, Priyali; Howes, Andrew M.] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA.
   [Losovskiy, Sofiya] Cleveland State Univ, Dept Chem, Cleveland, OH 44115 USA.
   [Gabyak, Vadym] Cleveland State Univ, Dept Biol Geol & Environm Sci, Cleveland, OH 44115 USA.
   [Salomon, Robert G.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
C3 Case Western Reserve University; Case Western Reserve University;
   Cleveland State University; Cleveland State University; Case Western
   Reserve University
RP Salomon, RG (通讯作者)，Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.; Salomon, RG (通讯作者)，Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
EM rgs@case.edu
OI Howes, Andrew/0000-0003-2365-3592; Salomon, Robert/0000-0001-9456-3557;
   Stiadle, Thomas/0000-0002-2934-9834; Cheng,
   Yu-Shiuan/0000-0002-7408-7888
FU NIH [R01-EY016813, P30 EY11373]; NATIONAL EYE INSTITUTE [P30EY011373,
   R01EY016813] Funding Source: NIH RePORTER
FX This work was supported by NIH Grant R01-EY016813 (to RG.S.) and Core
   Grant P30 EY11373 (to Case Visual Sciences Research Center).
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NR 88
TC 8
Z9 8
U1 2
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
EI 1520-5010
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD AUG
PY 2018
VL 31
IS 8
BP 666
EP 679
DI 10.1021/acs.chemrestox.8b00028
PG 14
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA GR3KR
UT WOS:000442489000007
PM 29883119
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Bennett, N
   John, L
   Likhar, N
   Agrawal, R
   Amoaku, WM
AF Bennett, Natalie
   John, Lokho
   Likhar, Nishkarsh
   Agrawal, Rumjhum
   Amoaku, Winfried M.
TI Clinical Efficacy and Safety of Current Interventions for Choroidal
   Neovascularization Associated with Rare Diseases: A Systematic
   Literature Review
SO ADVANCES IN THERAPY
LA English
DT Review
DE BCVA; Bevacizumab; Choroidal neovascularization; Ophthalmology;
   Photodynamic therapy; Ranibizumab; Systematic literature review; VEGF;
   Visual acuity
ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL AFLIBERCEPT INJECTION; MACULAR
   DEGENERATION; MULTIFOCAL CHOROIDITIS; OCULAR HISTOPLASMOSIS;
   PHOTODYNAMIC THERAPY; ANGIOID STREAKS; VISION LOSS; EXPRESSION; VEGF
AB The aim of this systematic literature review was to evaluate the efficacy and safety of interventions for the treatment of choroidal neovascularization (CNV) secondary to etiologies other than age-related macular degeneration and pathologic myopia.
   Relevant randomized controlled trials (RCTs) and prospective observational studies were identified by searching MEDLINE, MEDLINE In-Process, EMBASE, and CENTRAL.
   The search identified 5 RCTs; no relevant observational studies were identified. The studies differed in terms of underlying cause of CNV, patient numbers (n = 9-178), follow-up time (2-36 months) and quality assessment. In the largest RCT (n = 178 across a range of rare CNV etiologies), intravitreal ranibizumab showed superior efficacy versus sham from baseline to month 2 [mean best-corrected visual acuity (BCVA): + 9.5 vs. - 0.4 letters; p < 0.001]; the gain was maintained up to month 12. In the treatment of CNV secondary to presumed ocular histoplasmosis syndrome (POHS), both intravitreal ranibizumab and photodynamic therapy (PDT) showed significant improvement from baseline BCVA over the 12-month period (n = 9); however, all patients in the PDT group required rescue ranibizumab therapy. Unlicensed intravitreal bevacizumab was associated with a statistically significant improvement in BCVA compared to PDT at 12 months (p < 0.001) in patients with CNV secondary to multifocal choroiditis (n = 27). The use of steroids before PDT showed better BCVA outcomes than PDT alone (p < 0.05) in patients with idiopathic CNV (n = 20). Argon green laser therapy showed limited efficacy in patients with CNV secondary to OHS (n = 134).
   There is evidence from a relatively large, good-quality study to support the use of intravitreal ranibizumab for the treatment of CNV secondary to rare diseases. However, the limited number of RCTs for this indication and differences in study characteristics between RCTs mean that there is uncertainty regarding comparative clinical effectiveness of interventions. RCTs with an active comparator are required to fully establish the comparative effectiveness of treatments for CNV secondary to rare diseases.
   Novartis Pharmaceuticals UK Ltd, Surrey, UK.
C1 [Bennett, Natalie] Novartis Pharmaceut UK Ltd, 200 Frimley Business Pk, Camberley GU16 7SR, Surrey, England.
   [John, Lokho; Likhar, Nishkarsh; Agrawal, Rumjhum] Novartis Healthcare Pvt Ltd, Hyderabad, Telangana, India.
   [Amoaku, Winfried M.] Univ Nottingham, Univ Hosp, QMC, Ophthalmol,DCN,Eye & ENT Ctr, B Floor, Nottingham, England.
C3 Novartis; Novartis; Nottingham University Hospital NHS Trust; University
   of Nottingham
RP Bennett, N (通讯作者)，Novartis Pharmaceut UK Ltd, 200 Frimley Business Pk, Camberley GU16 7SR, Surrey, England.
EM natalie.bennett@novartis.com
OI Amoaku, Winfried/0000-0001-5028-7984
FU Novartis Pharmaceuticals UK Ltd, Surrey, UK; Novartis Pharmaceuticals UK
   Ltd.
FX This study was funded by Novartis Pharmaceuticals UK Ltd, Surrey, UK.
   Funding for the article processing charges was provided by Novartis
   Pharmaceuticals UK Ltd. All authors had full access to all of the data
   in this study and take complete responsibility for the integrity of the
   data and accuracy of the data analysis.
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NR 47
TC 3
Z9 4
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0741-238X
EI 1865-8652
J9 ADV THER
JI Adv. Ther.
PD MAY
PY 2018
VL 35
IS 5
BP 591
EP 603
DI 10.1007/s12325-018-0698-9
PG 13
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA GG6MC
UT WOS:000432809800001
PM 29687336
DA 2022-11-30
ER

PT J
AU Lorencatto, F
   Harper, AM
   Francis, JJ
   Lawrenson, JG
AF Lorencatto, Fabiana
   Harper, Alice M.
   Francis, Jill J.
   Lawrenson, John G.
TI A survey of UK optometry trainees' smoking cessation training
SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS
LA English
DT Article
DE education; optometry; smoking; smoking cessation; teaching; training
ID HEALTH-PROFESSIONALS; TOBACCO EDUCATION; INTERVENTIONS; GUIDELINES;
   ATTITUDES; OUTCOMES; PROGRAM; SCHOOLS; PEOPLE
AB Background: Smoking is a risk factor for a number of eye conditions, including age-related macular degeneration, cataracts and thyroid eye disease. Smoking cessation interventions have been shown to be highly cost-effective when delivered by a range of healthcare professionals. Optometrists are well placed to deliver smoking cessation advice to a wide population of otherwise healthy smokers. Yet optometrists remain a relatively neglected healthcare professional group in smoking cessation research and policy. Surveys of UK medical/nursing schools and of optometrists' training internationally demonstrate significant deficits in current curricular coverage regarding smoking cessation. This study aimed to identify the extent of smoking cessation training in UK optometry trainees' undergraduate and pre-registration training.
   Methods: All undergraduate optometry schools in the UK (n = 9) were invited to participate in a web-based survey of their curricular coverage and assessment related to smoking cessation, and of perceived barriers to delivering smoking cessation training. A content analysis of the College of Optometrists Scheme for Registration Trainee Handbook 2014 was conducted to identify competence indicators related to smoking cessation.
   Results: Nine undergraduate optometry schools (100%) responded to the survey. The majority reported dedicating limited hours (0-3) to teaching smoking cessation, and predominantly focused on teaching the harmful effects of smoking (89%). Only one school provides practical skills training for delivering evidence-based smoking cessation interventions, including very brief advice. The majority of schools (78%) reported that they did not formally examine students on their knowledge or skills for supporting smoking cessation, and rated confidence in their graduates' abilities to deliver smoking cessation interventions as 'poor' (78%). Lack of knowledge amongst staff was identified as the key barrier to teaching about smoking cessation support. The pre-registration competency framework does not include any competence indicators related to providing support for quitting smoking.
   Conclusions: There are substantial gaps in the current curricula of UK optometry training, particularly regarding practical skills for supporting smoking cessation. Increased curricular coverage of these issues is essential to ensure trainee optometrists are adequately trained and competent in supporting patients to quit smoking.
C1 [Lorencatto, Fabiana; Harper, Alice M.; Francis, Jill J.] City Univ London, Sch Hlth Sci, Ctr Hlth Serv Res, London, England.
   [Lawrenson, John G.] City Univ London, Sch Hlth Sci, Ctr Publ Hlth Res, London, England.
C3 City University London; City University London
RP Lorencatto, F (通讯作者)，City Univ London, Sch Hlth Sci, Ctr Hlth Serv Res, London, England.
EM Fabiana.lorencatto.2@city.ac.uk
RI Francis, Jill/AHE-6998-2022
OI Francis, Jill/0000-0001-5784-8895; Harper, Alice/0000-0001-5866-2128;
   Lawrenson, John/0000-0002-2031-6390
FU City University London Research Development Fund Project Grant
FX This work was supported by a City University London Research Development
   Fund Project Grant.
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   World Health Organisation (WHO), 2005, WHO INF M HLTH PROF
NR 44
TC 5
Z9 5
U1 0
U2 13
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-5408
EI 1475-1313
J9 OPHTHAL PHYSL OPT
JI Ophthalmic Physiol. Opt.
PD JUL
PY 2016
VL 36
IS 4
BP 494
EP 502
DI 10.1111/opo.12290
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DW3XU
UT WOS:000383577200017
PM 26920077
OA Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Malik, D
   Hsu, T
   Falatoonzadeh, P
   Caceres-del-Carpio, J
   Tarek, M
   Chwa, M
   Atilano, SR
   Ramirez, C
   Nesburn, AB
   Boyer, DS
   Kuppermann, BD
   Jazwinski, SM
   Miceli, MV
   Wallace, DC
   Udar, N
   Kenney, MC
AF Malik, Deepika
   Hsu, Tiffany
   Falatoonzadeh, Payam
   Caceres-del-Carpio, Javier
   Tarek, Mohamed
   Chwa, Marilyn
   Atilano, Shari R.
   Ramirez, Claudio
   Nesburn, Anthony B.
   Boyer, David S.
   Kuppermann, Baruch D.
   Jazwinski, S. Michal
   Miceli, Michael V.
   Wallace, Douglas C.
   Udar, Nitin
   Kenney, M. Cristina
TI Human Retinal Transmitochondrial Cybrids with J or H mtDNA Haplogroups
   Respond Differently to Ultraviolet Radiation: Implications for Retinal
   Diseases
SO PLOS ONE
LA English
DT Article
ID MITOCHONDRIAL-DNA HAPLOGROUPS; GROWTH-FACTOR-ALPHA; MACULAR
   DEGENERATION; PIGMENT EPITHELIUM; CELL-DEATH; ABERRANT ACCUMULATION;
   INFLAMMATORY CYTOKINE; NUCLEOTIDE EXCISION; COMPLEMENT-SYSTEM; OXIDATIVE
   STRESS
AB Background: It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation.
   Methodology/Principal Findings: Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho 0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids.
   Conclusion/Significance: In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be important to consider.
C1 [Malik, Deepika; Hsu, Tiffany; Falatoonzadeh, Payam; Caceres-del-Carpio, Javier; Tarek, Mohamed; Chwa, Marilyn; Atilano, Shari R.; Ramirez, Claudio; Nesburn, Anthony B.; Kuppermann, Baruch D.; Udar, Nitin; Kenney, M. Cristina] Univ Calif Irvine, Gavin Herbert Eye Inst, Irvine, CA 92697 USA.
   [Tarek, Mohamed] El Minya Univ, Dept Ophthalmol, El Minya, Egypt.
   [Nesburn, Anthony B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   [Boyer, David S.] Retina Vitreous Associates Med Grp, Beverly Hills, CA USA.
   [Jazwinski, S. Michal; Miceli, Michael V.] Tulane Univ, Tulane Ctr Aging, New Orleans, LA 70118 USA.
   [Wallace, Douglas C.] Univ Penn, Childrens Hosp Philadelphia, Ctr Mitochondrial & Epigen Med, Philadelphia, PA 19104 USA.
   [Wallace, Douglas C.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA.
   [Kenney, M. Cristina] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA.
C3 University of California System; University of California Irvine;
   Egyptian Knowledge Bank (EKB); Minia University; Cedars Sinai Medical
   Center; Retina Vitreous Associates Medical Group; Tulane University;
   University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of
   Philadelphia; University of Pennsylvania; University of California
   System; University of California Irvine
RP Kenney, MC (通讯作者)，Univ Calif Irvine, Gavin Herbert Eye Inst, Irvine, CA 92697 USA.
EM mkenney@uci.edu
OI Udar, Nitin/0000-0001-8533-9190; Atilano, Shari/0000-0002-7729-7864;
   CACERES DEL CARPIO, JAVIER/0000-0001-5673-5709; Moustafa, M.
   Tarek/0000-0003-4545-6012
FU Discovery Eye Foundation; Guenther Foundation; Beckman Initiative for
   Macular Research; Polly and Michael Smith Foundation; Max Factor Family
   Foundation; Skirball Foundation; Lincy Foundation, Iris; B. Gerald
   Cantor Foundation; Research to Prevent Blindness;  [AG006168]; NATIONAL
   INSTITUTE ON AGING [R37AG006168, R01AG006168] Funding Source: NIH
   RePORTER
FX This work was supported by Discovery Eye Foundation, Guenther
   Foundation, Beckman Initiative for Macular Research, Polly and Michael
   Smith Foundation, Max Factor Family Foundation, Skirball Foundation,
   Lincy Foundation, Iris and B. Gerald Cantor Foundation, and unrestricted
   grant from Research to Prevent Blindness. National Institute on Aging
   grant (AG006168) to SMJ and MVM. The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 69
TC 27
Z9 29
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 11
PY 2014
VL 9
IS 6
AR e99003
DI 10.1371/journal.pone.0099003
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AK7TQ
UT WOS:000338631000039
PM 24919117
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Jonas, JB
   Nangia, V
   Matin, A
   Bhojwani, K
   Sinha, A
   Khare, A
   Agarwal, S
   Bhate, K
AF Jonas, Jost B.
   Nangia, Vinay
   Matin, Arshia
   Bhojwani, Krishna
   Sinha, Ajit
   Khare, Anshu
   Agarwal, Shubhra
   Bhate, Karishma
TI Pseudoexfoliation: Normative Data and Associations. The Central India
   Eye and Medical Study
SO PLOS ONE
LA English
DT Article
ID POPULATION-BASED SURVEY; ANGLE-CLOSURE GLAUCOMA; EXFOLIATION SYNDROME;
   INTRAOCULAR-PRESSURE; OCCLUDABLE ANGLES; THESSALONIKI EYE; CHINESE
   PEOPLE; SOUTHERN INDIA; PREVALENCE; CHAMBER
AB Purpose: To assess the prevalence of pseudoexfoliation (PEX) and its associations in a population-based setting.
   Design: Population-based, cross-sectional study.
   Methods: The Central India Eye and Medical Study included 4711 individuals. All study participants underwent a detailed ophthalmological examination. After medical pupil dilation, PEX was assessed by an experienced ophthalmologist using slit-lamp based biomicroscopy.
   Results: Slit lamp examination results were available for 4646 (98.6%) study participants with a mean age of 49.3 +/- 13.3 years (range: 30-100 years). PEX was detected in 87 eyes (prevalence: 0.95 +/- 0.10% (95% CI: 0.75, 1.15) of 69 subjects (prevalence: 1.49 +/- 0.18% (95% CI: 1.14, 1.83). PEX prevalence increased significantly (P<0.001) from 0% in the age group of 30-39 years, to 2.85 +/- 0.56% in the age group of 60-69 years, to 6.60 +/- 1.21% in the age group of 70-79 years, and to 12.3 +/- 4.11% in the age group of 80+ years. In multivariate analysis, PEX prevalence was associated with higher age (P<0.001; regression coefficient B:0.11; odds ratio (OR): 1.11 (95% CI: 1.09, 1.13)), lower body mass index (P = 0.001; B:-0.12; OR: 0.88 (95CI: 0.82, 0.95)) and higher diastolic blood pressure (P = 0.002; B: 0.02; OR: 1.03 (95% CI: 1.01, 1.04)). In the multivariate analysis, PEX was not associated with retinal nerve fiber layer cross section area (P = 0.76) and presence of open-angle glaucoma (P = 0.15).
   Conclusions: In a rural Central Indian population aged 30+ years, PEX prevalence (mean: 1.49 +/- 0.18%) was significantly associated with older age, lower body mass index and higher diastolic blood pressure. It was not significantly associated with optic nerve head measurements, refractive error, any ocular biometric parameter, nuclear cataract, early age-related macular degeneration and retinal vein occlusion, diabetes mellitus, smoking, and dyslipidemia.
C1 [Jonas, Jost B.; Nangia, Vinay; Matin, Arshia; Bhojwani, Krishna; Sinha, Ajit; Khare, Anshu; Agarwal, Shubhra; Bhate, Karishma] Suraj Eye Inst, Nagpur, Maharashtra, India.
   [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany.
C3 Suraj Eye Institute; Ruprecht Karls University Heidelberg
RP Jonas, JB (通讯作者)，Suraj Eye Inst, Nagpur, Maharashtra, India.
EM Jost.Jonas@medma.uni-heidelberg.de; nagpursuraj@gmail.com
RI Bhate, Karishma/AAD-8609-2019
FU Om Drishti Trust, Nagpur, India; Heidelberg Engineering Co., Heidelberg,
   Germany; Rotary Sight Saver Netherlands; ORBIS International; Carl Zeiss
   Meditec Co., Jena, Germany
FX Supported by an unrestricted grant from Om Drishti Trust, Nagpur, India;
   Heidelberg Engineering Co., Heidelberg, Germany; Rotary Sight Saver
   Netherlands; ORBIS International; and Carl Zeiss Meditec Co., Jena,
   Germany. The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
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NR 37
TC 36
Z9 37
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 21
PY 2013
VL 8
IS 10
AR e76770
DI 10.1371/journal.pone.0076770
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 239NN
UT WOS:000326032600010
PM 24204672
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Yin, LL
   Wu, XW
   Gong, YY
   Shi, YH
   Qiu, YT
   Zhang, HM
   Liu, XJ
   Gu, Q
AF Yin, Lili
   Wu, Xingwei
   Gong, Yuanyuan
   Shi, Yuhua
   Qiu, Yating
   Zhang, Hongmei
   Liu, Xiaojuan
   Gu, Qing
TI OX-LDL Up-Regulates the Vascular Endothelial Growth Factor-to-Pigment
   Epithelium-Derived Factor Ratio in Human Retinal Pigment Epithelial
   Cells
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Mitogen-activated protein kinases;
   Oxidized low-density lipoprotein; Pigment epithelium-derived factor;
   Retinal pigment epithelial cells; Vascular endothelial growth factor
ID AGE-RELATED MACULOPATHY; BLUE MOUNTAINS EYE; CARDIOVASCULAR
   RISK-FACTORS; LOW-DENSITY LIPOPROTEINS; MACULAR DEGENERATION; OXIDIZED
   LDL; CHOROIDAL NEOVASCULARIZATION; VISUAL IMPAIRMENT; FACTOR EXPRESSION;
   HUMAN MACROPHAGES
AB Purpose: Native and oxidized (OX) low-density lipoprotein (LDL) may contribute to the pathogenesis of age related macular degeneration (AMD). In this study, we investigated the effects of lipoproteins, including LDL and ox-LDL, on cell viability, apoptosis, and vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) expression in cultured human retinal pigment epithelial (RPE) cells.
   Method: ARPE-19 cells were incubated with 10-100 mg/ml n-LDL, ox-LDL for 24 hr. Cell viability was assessed using the Cell Titer 96 Aqueous One Solution cell proliferation assay. The apoptosis of RPE was measured with TUNEL. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the levels of VEGF and PEDF mRNA in RPE cells. The expression of VEGF and PEDF protein was measured by western blotting. To examine the role of MAPK signal transduction in LDL- and OX-LDL-induced VEGF and PEDF protein expression, ARPE-19 cells were pretreated with one of several MAPK inhibitors for 2 hr and then incubated with native LDL or OX-LDL for 24 hr. One-way analysis of variance was used to compare the differences.
   Results: OX-LDL treatment decreased ARPE-19 cell viability in a dose-dependent manner, whereas native LDL had no effect. Incubation of ARPE-19 cells with 10 mg/mL OX-LDL induced marked apoptosis, compared with untreated control cells. OX-LDL also increased VEGF expression and decreased PEDF expression, whereas native LDL had no significant effect. The VEGF-to-PEDF ratio was elevated after OX-LDL treatment. OX-LDL-induced VEGF protein synthesis was partly abolished by inhibiting p38 and JNK, while inhibiting ERK did not show a significant effect. Conclusions: OX-LDL treatment induced cellular changes in ARPE-19 cells that appeared to reflect pathogenic events in neovascular AMD, providing potential insight into the roles of OX-LDL in human RPE cells and its potential role in the pathogenesis of AMD.
C1 [Yin, Lili; Wu, Xingwei; Gong, Yuanyuan; Shi, Yuhua; Qiu, Yating; Zhang, Hongmei; Liu, Xiaojuan; Gu, Qing] Shanghai Jiao Tong Univ, Affiliated Shanghai Peoples Hosp 1, Dept Ophthalmol, Shanghai 200030, Peoples R China.
C3 Shanghai Jiao Tong University
RP Wu, XW (通讯作者)，Shanghai Jiao Tong Univ, Affiliated Shanghai Peoples Hosp 1, Dept Ophthalmol, Shanghai 200030, Peoples R China.
EM wuxingwei2010@tom.com
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NR 54
TC 16
Z9 19
U1 0
U2 7
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD APR
PY 2011
VL 36
IS 4
BP 379
EP 385
DI 10.3109/02713683.2010.537427
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 735BW
UT WOS:000288389400013
PM 21348596
DA 2022-11-30
ER

PT J
AU Sarraf, D
   Reddy, S
   Chiang, A
   Yu, F
   Jain, A
AF Sarraf, David
   Reddy, Shantan
   Chiang, Allen
   Yu, Fei
   Jain, Atul
TI A NEW GRADING SYSTEM FOR RETINAL PIGMENT EPITHELIAL TEARS
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE AMD; retinal pigment epithelial tear; anti-VEGF therapy
ID INTRAVITREAL BEVACIZUMAB INJECTION; MACULAR DEGENERATION; RANIBIZUMAB;
   AVASTIN; SECONDARY
AB Purpose: The purpose of this study was to assess the prognostic value of a new grading system for retinal pigment epithelium (RPE) tears that developed after antivascular endothelial growth factor (VEGF) therapy for exudative age-related macular degeneration.
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   Results: Twenty-one eyes from 20 patients were evaluated in this study. Retinal pigment epithelium tears were graded from one to four based on the greatest length in the vector direction of the tear and involvement of the fovea. Nineteen percent (n = 4) of eyes had Grade 1 tears (diameter smaller than 200 mm), 14% (n = 3) had Grade 2 tears (diameter between 200 mm and 1-disk diameter), 19% (n = 4) had Grade 3 tears (diameter greater than 1-disk diameter), and 48% (n = 10) had Grade 4 tears (Grade 3 tears that involved the foveal center). Lower grade tears were more likely to have better visual acuity and better response to continued anti-VEGF therapy and less likely to develop a disciform scar but were at risk of progressing to a higher grade tear over time.
   Conclusion: The grading of RPE tears according to greatest linear diameter may have prognostic value in predicting visual acuity and anatomical outcome with or without continued anti-VEGF therapy. Lower grade tears have better visual acuity and response to anti-VEGF therapy. Grade 4 tears have a very poor prognosis with or without anti-VEGF therapy. RETINA 30:1039-1045, 2010
C1 [Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA.
   [Sarraf, David] Greater VA Los Angeles Healthcare Ctr, Los Angeles, CA USA.
   [Sarraf, David] Kaiser Permanente, Woodland Hills, CA USA.
   [Reddy, Shantan] NYU, Langone Med Ctr, New York, NY USA.
C3 University of California System; University of California Los Angeles;
   University of California Los Angeles Medical Center; David Geffen School
   of Medicine at UCLA; Kaiser Permanente; New York University; NYU Langone
   Medical Center
RP Sarraf, D (通讯作者)，Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA.
EM dsarraf@ucla.edu
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NR 20
TC 66
Z9 70
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD JUL-AUG
PY 2010
VL 30
IS 7
BP 1039
EP 1045
DI 10.1097/IAE.0b013e3181cdf366
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 622CE
UT WOS:000279635600007
PM 20458264
DA 2022-11-30
ER

PT J
AU Tabel, M
   Wolf, A
   Szczepan, M
   Xu, HP
   Jagle, H
   Moehle, C
   Chen, M
   Langmann, T
AF Tabel, Mona
   Wolf, Anne
   Szczepan, Manon
   Xu, Heping
   Jaegle, Herbert
   Moehle, Christoph
   Chen, Mei
   Langmann, Thomas
TI Genetic targeting or pharmacological inhibition of galectin-3 dampens
   microglia reactivity and delays retinal degeneration
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Galectin-3 deficiency; Galectin-3 inhibition; TD139; Microglia; Retinal
   degeneration; Light damage
ID MACULAR DEGENERATION; LUNG FIBROSIS; ACTIVATION; IMPAIRMENT; CELLS
AB Background Dysfunctional humoral and cellular innate immunity are key components in the development and progression of age-related macular degeneration (AMD). Specifically, chronically activated microglia and their disturbed regulatory system contribute to retinal degeneration. Galectin-3, a beta-galactose binding protein, is a potent driver of macrophage and microglia activation and has been implicated in neuroinflammation, including neurodegenerative diseases of the brain. Here, we hypothesized that genetic deficiency of galectin-3 or its modulation via TD139 dampens mononuclear phagocyte reactivity and delays retinal degeneration. Methods Galectin-3 expression in AMD patients was analyzed by immunohistochemical stainings. Galectin-3 knockout and BALB/cJ mice were exposed to white bright light with an intensity of 15,000 lux for 1 h and Cx3cr1(GFP/+) mice to focal blue light of 50,000 lux for 10 min. BALB/cJ and Cx3cr1(GFP/+) mice received intraperitoneal injections of 15 mg/kg TD139 or vehicle for five consecutive days, starting one day prior to light exposure. The effects of galectin-3 deficiency or inhibition on microglia were analyzed by immunohistochemical stainings and in situ hybridization of retinal sections and flat mounts. Pro-inflammatory cytokine levels in the retina and retinal pigment epithelium (RPE) were quantified by qRT-PCR and transcriptomic changes were analyzed by RNA-sequencing. Retinal thickness and structure were evaluated by optical coherence tomography. Results We found that galectin-3 expression was strongly upregulated in reactive retinal mononuclear phagocytes of AMD patients and in the two related mouse models of light-induced retinal degeneration. The experimental in vivo data further showed that specific targeting of galectin-3 by genetic knockout or administration of the small-molecule inhibitor TD139 reduced microglia reactivity and delayed retinal damage in both light damage conditions. Conclusion This study defines galectin-3 as a potent driver of retinal degeneration and highlights the protein as a drug target for ocular immunomodulatory therapies.
C1 [Tabel, Mona; Wolf, Anne; Langmann, Thomas] Univ Cologne, Fac Med, Dept Ophthalmol, Lab Expt Immunol Eye, Cologne, Germany.
   [Tabel, Mona; Wolf, Anne; Langmann, Thomas] Univ Hosp Cologne, Cologne, Germany.
   [Szczepan, Manon; Xu, Heping; Chen, Mei] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Wellcome Wolfson Inst Expt Med, Belfast, Antrim, North Ireland.
   [Jaegle, Herbert] Univ Eye Clin Regensburg, Dept Ophthalmol, Regensburg, Germany.
   [Moehle, Christoph] Univ Regensburg, Ctr Excellence Fluorescent Bioanalyt, Regensburg, Germany.
   [Langmann, Thomas] Univ Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany.
C3 University of Cologne; University of Cologne; Queens University Belfast;
   University of Regensburg; University of Regensburg; University of
   Cologne
RP Langmann, T (通讯作者)，Univ Cologne, Fac Med, Dept Ophthalmol, Lab Expt Immunol Eye, Cologne, Germany.; Langmann, T (通讯作者)，Univ Hosp Cologne, Cologne, Germany.; Langmann, T (通讯作者)，Univ Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany.
EM thomas.langmann@uk-koeln.de
OI Xu, Heping/0000-0003-4000-931X
FU Ruhling-Stiftung und Brunenbusch-Stein Stiftung; Fight for Sight UK
   [5105/5106]; DFG (German Research Foundation) [491454339]; Deutsche
   Forschungsgemeinschaft [FOR2240]; Pro Retina Foundation; Erhard Ruther
   Foundation; Velux Foundation [967]; Dr. Gaide-Foundation; Projekt DEAL
FX Open Access funding enabled and organized by Projekt DEAL. This project
   is financed by Ruhling-Stiftung und Brunenbusch-Stein Stiftung and Fight
   for Sight UK (reference 5105/5106). The article processing charge is
   financed by the DFG (German Research Foundation, no 491454339). The
   research of the laboratory is supported by the Deutsche
   Forschungsgemeinschaft (FOR2240), the Pro Retina Foundation, the Erhard
   Ruther Foundation, the Dr. Gaide-Foundation, and the Velux Foundation
   (Project 967).
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NR 47
TC 0
Z9 0
U1 0
U2 0
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD SEP 17
PY 2022
VL 19
IS 1
AR 229
DI 10.1186/s12974-022-02589-6
PG 19
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA 4O7DS
UT WOS:000854854300001
PM 36115971
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Cho, H
   Choi, KS
   Lee, JY
   Lee, D
   Choi, NK
   Lee, Y
   Bae, S
AF Cho, HyunJeong
   Choi, Kyung Seek
   Lee, Joo Yong
   Lee, Donghwan
   Choi, Nam-Kyong
   Lee, YouKyung
   Bae, SeungJin
TI Healthcare resource use and costs of diabetic macular oedema for
   patients with antivascular endothelial growth factor versus a
   dexamethasone intravitreal implant in Korea: a population-based study
SO BMJ OPEN
LA English
DT Article
DE diabetic macular edema; population-based study; resource utilization;
   cost of illness; Korea; agencies regulation
ID QUALITY-OF-LIFE; BEVACIZUMAB; RANIBIZUMAB; AFLIBERCEPT; RETINOPATHY;
   MANAGEMENT; BURDEN; TRIAL
AB Objectives To estimate the costs and healthcare resources of patients with diabetic macular oedema (DME) who received intravitreal antivascular endothelial growth factor (anti-VEGF) agents or a dexamethasone intravitreal implant (DEX-implant) in Korea.
   Design Retrospective cohort study.
   Setting The Korean National Health Insurance claim data from 1 January 2015 to 30 June 2017 were retrieved from the Health Insurance Review and Assessment Service.
   Participants Adult patients with DME who were diagnosed with diabetic retinopathy or DME and received ranibizumab, aflibercept or a DEX-implant in conjunction with intravitreal injection were included. Patients whose primary diagnoses were age-related macular degeneration or retinal vein occlusion were excluded.
   Main outcome measures Healthcare resource utilisation and costs related to DME in the 12-month postindex period.
   Results During the study period, 182 patients and 414 patients were identified in the anti-VEGF and DEX-implant groups, respectively, and there was no significant difference in the demographic characteristics between the two groups. The outpatient eye care-related medical costs were US$3002.33 for the anti-VEGF group vs US$2250.35 for the DEX-implant group (p<0.0001). After adjusting the relevant covariates based on the generalised linear model, the estimated outpatient eye care-related medical costs were 33% higher in the anti-VEGF group than in the DEX-implant group (p<0.0001, 95% CI 22% to 45%). The utilisation pattern of the two groups showed no significant difference except for the number of intravitreal injections, which was higher in the anti-VEGF group (2.692.29) than in the DEX-implant group (2.09 +/- 1.37, p<0.001).
   Conclusion The average annual eye-related medical cost of the DEX-implant group was significantly lower than that of the anti-VEGF group during the study period, which was mainly due to decreased utilisation of eye care-related injections. Further long-term studies are needed.
C1 [Cho, HyunJeong; Bae, SeungJin] Ewha Womans Univ, Coll Pharm, Seoul, South Korea.
   [Choi, Kyung Seek] Soonchunhyang Univ Hosp, Dept Ophthalmol, Seoul, South Korea.
   [Lee, Joo Yong] Asan Med Ctr, Dept Ophthalmol, Seoul, South Korea.
   [Lee, Donghwan] Ewha Womans Univ, Dept Stat, Seoul, South Korea.
   [Choi, Nam-Kyong] Ewha Womans Univ, Dept Hlth Convergence, Seoul, South Korea.
   [Lee, YouKyung] Allergan Korea Ltd, Seoul, South Korea.
C3 Ewha Womans University; Soonchunhyang University; Soonchunhyang
   University Hospital; University of Ulsan; Asan Medical Center; Ewha
   Womans University; Ewha Womans University; AbbVie; Allergan
RP Bae, S (通讯作者)，Ewha Womans Univ, Coll Pharm, Seoul, South Korea.
EM sjbae@ewha.ac.kr
RI Bae, SeungJin/J-6011-2016
OI Bae, SeungJin/0000-0002-8993-8884
FU Allergan Korea
FX This study was financially supported by Allergan Korea.
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NR 36
TC 8
Z9 8
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PD SEP
PY 2019
VL 9
IS 9
AR e030930
DI 10.1136/bmjopen-2019-030930
PG 8
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA JO7XE
UT WOS:000497787600324
PM 31542758
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Senger, DR
   Hoang, MV
   Kim, KH
   Li, CS
   Cao, SG
AF Senger, Donald R.
   Hoang, Mien V.
   Kim, Ki Hyun
   Li, Chunshun
   Cao, Shugeng
TI Anti-inflammatory activity of Barleria lupulina: Identification of
   active compounds that activate the Nrf2 cell defense pathway, organize
   cortical actin, reduce stress fibers, and improve cell junctions in
   microvascular endothelial cells
SO JOURNAL OF ETHNOPHARMACOLOGY
LA English
DT Article
DE Barleria lupulina; Traditional medicine; Nrf2; 4-Methylcatechol;
   4-Vinylcatechol; 4-Ethylcatechol; Microvascular endothelial cells;
   Endothelial barrier function; Actin cytoskeleton
ID RHO-KINASE INHIBITOR; OXIDATIVE STRESS; TYROSINE PHOSPHORYLATION;
   TRANSCRIPTION FACTOR; ADHERENS JUNCTIONS; IRIDOID GLUCOSIDES; TIGHT
   JUNCTIONS; OXIDANT STRESS; VE-CADHERIN; LUNG INJURY
AB Ethnopharmacological relevance: Hot aqueous extracts of the plant Barleria lupulina (BL) are used for treating inflammatory conditions and diabetic vascular complications.
   Aim of the Study: The goal was to identify active compounds in hot aqueous extracts of BL (HAE-BL) that are consistent with a role in reducing inflammation and reducing the vascular pathology associated with diabetes. In particular, we examined activation of the Nrf2 cell defense pathway because our initial findings indicated that HAE-BL activates Nrf2, and because Nrf2 is known to suppress inflammation. Activation of Nrf2 by HAE-BL has not been described previously.
   Materials and methods: Human endothelial cells, real-time PCR, western blotting, cytoskeletal analyses, and assay-guided fractionation with HPLC were used to identify specific compounds in HAE-BL that activate the Nrf2 cell defense pathway and reduce markers of inflammation in vitro.
   Results: HAE-BL potently activated the Nrf2 cell defense pathway in endothelial cells consistent with its traditional use and reported success in reducing inflammation. Assay guided fractionation with HPLC identified three alkyl catechols: 4-ethylcatechol, 4-vinylcatechol, and 4-methylcatechol, that are each potent Nrf2 activators. In addition to activating Nrf2, HAE-BL and akyl catechols each profoundly improved organization of the endothelial cell actin cytoskeleton, reduced actin stress fibers, organized cell cell junctions, and induced expression of mRNA encoding claudin-5 that is important for formation of endothelial tight junctions and reducing vascular leak.
   Conclusions: HAE-BL contains important alkyl catechols that potently activate the Nrf2 cell defense pathway, improve organization of the endothelial cell cytoskeleton, and organize tight cell junctions. All of these properties are consistent with a role in reducing inflammation and reducing vascular leak. Because activation of the Nrf2 cell defense pathway also prevents cancers, neuro-degeneration, age related macular degeneration, and also reduces the severity of chronic obstructive pulmonary disorder and multiple sclerosis, HAE-BL warrants additional consideration for these other serious disorders. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Senger, Donald R.; Hoang, Mien V.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA.
   [Senger, Donald R.; Hoang, Mien V.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, 330 Brookline Ave, Boston, MA 02215 USA.
   [Kim, Ki Hyun] Sungkyunkwan Univ, Sch Pharm, Suwon 440746, Gyeonggi Do, South Korea.
   [Li, Chunshun; Cao, Shugeng] Univ Hawaii, Dept Pharmaceut Sci, Daniel K Inouye Coll Pharm, 200 W Kawili St, Hilo, HI 96720 USA.
C3 Harvard University; Beth Israel Deaconess Medical Center; Harvard
   Medical School; Harvard University; Beth Israel Deaconess Medical
   Center; Harvard Medical School; Sungkyunkwan University (SKKU);
   University of Hawaii System; University Hawaii Hilo
RP Cao, SG (通讯作者)，Univ Hawaii, Dept Pharmaceut Sci, Daniel K Inouye Coll Pharm, 200 W Kawili St, Hilo, HI 96720 USA.
EM scao@hawaii.edu
RI Hoang, Mien V/H-8270-2012
OI Hoang, Mien V/0000-0003-0859-2170
FU National Center for Complementary and Integrative Health (NCCIH) at the
   National Institutes of Health [R01AT007022]; National Center for
   Complementary & Integrative Health [R01AT007022] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM103466]
   Funding Source: NIH RePORTER
FX This publication was made possible by grant number R01AT007022 (to
   D.R.S. and S.C.) from the National Center for Complementary and
   Integrative Health (NCCIH) at the National Institutes of Health. Its
   contents are solely the responsibility of the authors and do not
   necessarily represent the official views of NCCIH. We thank Dr.
   Shou-Ching Jaminet and Dan Li of the Multi Gene Transcriptional
   Profiling Core at Beth Israel Deaconess Medical Center for expert
   RT-PCR.
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NR 84
TC 14
Z9 14
U1 2
U2 24
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0378-8741
EI 1872-7573
J9 J ETHNOPHARMACOL
JI J. Ethnopharmacol.
PD DEC 4
PY 2016
VL 193
BP 397
EP 407
DI 10.1016/j.jep.2016.09.017
PG 11
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
   Medicine; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
   Medicine
GA ED7ZF
UT WOS:000389090600043
PM 27660013
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Ranjbar, M
   Brinkmann, MP
   Zapf, D
   Miura, Y
   Rudolf, M
   Grisanti, S
AF Ranjbar, Mandy
   Brinkmann, Max Philipp
   Zapf, Dorinja
   Miura, Yoko
   Rudolf, Martin
   Grisanti, Salvatore
TI Fc Receptor Inhibition Reduces Susceptibility to Oxidative Stress in
   Human RPE Cells Treated with Bevacizumab, but not Aflibercept
SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
LA English
DT Article
DE Aflibercept; Bevacizumab; FcR; Oxidative stress; ROS; VEGF-A
ID ENDOTHELIAL GROWTH-FACTOR; AUTOCRINE SURVIVAL FACTOR; PIGMENT
   EPITHELIAL-CELLS; FACTOR VEGF; IN-VITRO; EXPRESSION; PROLIFERATION;
   RANIBIZUMAB; ACTIVATION; ATROPHY
AB Background/Aims: VEGF-A is induced by oxidative stress, and functions as a survival factor for various cell types, including retinal pigment epithelial (RPE) cells. Anti-vascular endothelial growth factor (VEGF) drugs like aflibercept and bevacizumab have shown to be most effective in treating neovascular age-related macular degeneration (AMD), however uptake of the drugs might lead to interference with cell physiology. Herein, we evaluated the significance of the Fc receptor (FcR) within this context and moreover explored the impact of VEGF inhibition under normal conditions as well as under oxidative stress, in terms of potential adverse effects. Methods: ARPE-19 (human RPE) cells were treated with aflibercept and bevacizumab in presence or absence of H2O2 as oxidative stress stimulus. After 24h cells were evaluated for drug uptake, VEGF-A expression and secretion, levels of intracellular reactive oxygen species (ROS) as well as cell proliferation. Experiments were repeated with cells being pre-incubated with an FcR inhibitor prior to drug application. Results: Both drugs inhibited extracellular levels of VEGF-A and were taken up into the RPE, resulting in significantly reduced intracellular levels of VEGF-A. When oxidative stress was applied, intracellular ROS levels in cells treated with both drugs rose, and cell proliferation was reduced. Prior incubation with the FcR inhibitor lessened the uptake of bevacizumab, but not aflibercept into RPE cells, and simultaneously enhanced cell survival under oxidative stress conditions. Conclusions: Our results indicate that uptake and accumulation of aflibercept and bevacizumab within RPE cells affect the intracellular VEGF-A metabolism negatively, leading to a biologically relevant reduced cell survival under oxidative stress. The FcR plays a substantial role in the uptake of bevacizumab, but not aflibercept, which allows an enhanced RPE cell survival through FcR blockage in an environment dominated by oxidative stress, as clinically significant for various inflammatory retinal disorders. (C) 2016 The Author(s) Published by S. Karger AG, Basel
C1 [Ranjbar, Mandy; Miura, Yoko; Rudolf, Martin; Grisanti, Salvatore] Med Univ Lubeck, Dept Ophthalmol, D-23538 Lubeck, Germany.
   [Ranjbar, Mandy; Brinkmann, Max Philipp; Zapf, Dorinja] Med Univ Lubeck, Lab Angiogenesis & Ocular Cell Transplantat, D-23538 Lubeck, Germany.
   [Miura, Yoko] Med Univ Lubeck, Inst Biomed Opt, D-23538 Lubeck, Germany.
C3 University of Lubeck; University of Lubeck; University of Lubeck
RP Ranjbar, M (通讯作者)，Med Univ Lubeck, Dept Ophthalmol, Lab Angiogenesis & Ocular Cell Transplantat, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
EM eye.research101@gmail.com
RI Miura, Yoko/B-5588-2015; Brinkmann, Max/AAA-1171-2021
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NR 37
TC 19
Z9 19
U1 0
U2 4
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1015-8987
EI 1421-9778
J9 CELL PHYSIOL BIOCHEM
JI Cell. Physiol. Biochem.
PY 2016
VL 38
IS 2
BP 737
EP 747
DI 10.1159/000443030
PG 11
WC Cell Biology; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Physiology
GA DF1ER
UT WOS:000371082300024
PM 26871551
OA gold
DA 2022-11-30
ER

PT J
AU Bonilha, VL
   Bell, BA
   Rayborn, ME
   Yang, XP
   Kaul, C
   Grossman, GH
   Samuels, IS
   Hollyfield, JG
   Xie, CS
   Cai, HB
   Shadrach, KG
AF Bonilha, Vera L.
   Bell, Brent A.
   Rayborn, Mary E.
   Yang, Xiaoping
   Kaul, Charlie
   Grossman, Gregory H.
   Samuels, Ivy S.
   Hollyfield, Joe G.
   Xie, Chengsong
   Cai, Huaibin
   Shadrach, Karen G.
TI Loss of DJ-1 elicits retinal abnormalities, visual dysfunction, and
   increased oxidative stress in mice
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE DJ-1 knockout; Retina; Morphology; Physiology; Histology;
   Immunohistology; Biochemistry; Oxidation
ID ONSET PARKINSONS-DISEASE; LIGHT-EVOKED RESPONSES; PIGMENT EPITHELIUM;
   MACULAR DEGENERATION; DROSOPHILA DJ-1; BRUCHS MEMBRANE; GEOGRAPHIC
   ATROPHY; CELL-DEATH; MITOCHONDRIAL LOCALIZATION; ANTIOXIDATIVE STRESS
AB DJ-1/PARK7 mutations or deletions cause autosomal recessive early onset Parkinson's disease (PD). Thus, DJ-1 protein has been extensively studied in brain and neurons. PD patients display visual symptoms; however, the visual symptoms specifically attributed to PD patients carrying DJ-1/PARK7 mutations are not known. In this study, we analyzed the structure and physiology of retinas of 3- and 6-month-old DJ-1 knockout (KO) mice to determine how loss of function of DJ-1 specifically contributes to the phenotypes observed in PD patients. As compared to controls, the DJ-1 KO mice displayed an increase in the amplitude of the scotopic ERG b-wave and cone ERG, while the amplitude of a subset of the dc-ERG components was decreased. The main structural changes in the DJ-1 KO retinas were found in the outer plexiform layer (OPL), photoreceptors and retinal pigment epithelium (RPE), which were observed at 3 months and progressively increased at 6 months. RPE thinning and structural changes within the OPL were observed in the retinas in DJ-1 KO mice. DJ-1 KO retinas also exhibited disorganized outer segments, central decrease in red/green cone opsin staining, decreased labeling of ezrin, broader distribution of ribeye labeling, decreased tyrosine hydroxylase in dopaminergic neurons, and increased 7,8-dihydro-8-oxoguanine-labeled DNA oxidation. Accelerated outer retinal atrophy was observed in DJ-1 KO mice after selective oxidative damage induced by a single tail vein injection of NaIO3, exposing increased susceptibility to oxidative stress. Our data indicate that DJ-1-deficient retinas exhibit signs of morphological abnormalities and physiological dysfunction in association with increased oxidative stress. Degeneration of RPE cells in association with oxidative stress is a key hallmark of age-related macular degeneration (AMD). Therefore, in addition to detailing the visual defects that occur as a result of the absence of DJ-1, our data is also relevant to AMD pathogenesis. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Bonilha, Vera L.; Hollyfield, Joe G.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Dept Ophthalmol, Cleveland, OH 44106 USA.
   [Bonilha, Vera L.; Bell, Brent A.; Rayborn, Mary E.; Yang, Xiaoping; Kaul, Charlie; Grossman, Gregory H.; Samuels, Ivy S.; Hollyfield, Joe G.; Shadrach, Karen G.] Cleveland Clin, Cole Eye Inst, Dept Ophthalm Res, Cleveland, OH 44106 USA.
   [Samuels, Ivy S.] Louis Stokes Cleveland Vet Affairs Med Ctr, Res Serv, Cleveland, OH USA.
   [Xie, Chengsong; Cai, Huaibin] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
C3 Case Western Reserve University; Cleveland Clinic Foundation; Cleveland
   Clinic Foundation; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); Case Western Reserve University; Louis Stokes
   Cleveland Veterans Affairs Medical Center; National Institutes of Health
   (NIH) - USA; NIH National Institute on Aging (NIA)
RP Bonilha, VL (通讯作者)，Cleveland Clin, Cole Eye Inst, Dept Ophthalm Res, Cleveland, OH 44106 USA.
EM bonilhav@ccf.org
RI Cai, Huaibin/H-3359-2013; Bonilha, Vera/AAS-8566-2020; Grossman, Gregory
   H/AAO-3525-2021
OI Cai, Huaibin/0000-0002-8596-6108; Bonilha, Vera/0000-0002-6166-5124;
   Grossman, Gregory H/0000-0003-1511-7028
FU NIH [EY017153]; Department of Veteran's Affairs CDA-2; Research to
   Prevent Blindness; Wolf Family Foundation; Intramural Research Program
   of National Institute on Aging [Z01-AG000945]; NATIONAL EYE INSTITUTE
   [R21EY017153] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGING
   [ZIAAG000943, Z01AG000945, ZIAAG000945, ZIAAG000928] Funding Source: NIH
   RePORTER
FX The authors thank Dr. Neal Peachey for comments on the manuscript. This
   work is a continuation of studies funded by the NIH grant EY017153
   (VLB). This work was also supported by a Department of Veteran's Affairs
   CDA-2 (ISS), an unrestricted grant from the Research to Prevent
   Blindness, by the Wolf Family Foundation, and partially supported by the
   Intramural Research Program of National Institute on Aging
   (Z01-AG000945) (HC).
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NR 81
TC 31
Z9 34
U1 0
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD OCT
PY 2015
VL 139
BP 22
EP 36
DI 10.1016/j.exer.2015.07.014
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CS0VW
UT WOS:000361781300003
PM 26215528
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Stewart, EA
   Wei, RX
   Branch, MJ
   Sidney, LE
   Amoaku, WM
AF Stewart, Elizabeth A.
   Wei, Ruoxin
   Branch, Matthew J.
   Sidney, Laura E.
   Amoaku, Winfried M.
TI Expression of Toll-like receptors in human retinal and choroidal
   vascular endothelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Toll-like receptor; Age-related macular degeneration; Choroidal
   endothelial cell; Retinal endothelial cell; Il-6
ID MACULAR DEGENERATION; EPITHELIAL-CELLS; SURFACE EXPRESSION; SIGNALING
   PATHWAYS; DENDRITIC CELLS; INNATE IMMUNITY; TLR3; ACTIVATION; DISEASE;
   TOLL-LIKE-RECEPTOR-4
AB Toll-like receptors (TLRs) are a family of proteins that initiate the innate immune response in reaction to invading microbes. Studies confirm the expression of TLRs in a variety of ocular tissues and cells, and it has also been suggested that selected TLRs may be associated with geographic atrophy and neovascularisation in age-related macular degeneration, diabetic retinopathy and other vascular and inflammatory diseases of the ocular posterior segment. However, TLR expression and localisation in the retinal and choroidal vasculature has not been defined. A better understanding of differential TLR expression in the choroid and retina, particularly in endothelial cells would improve our knowledge of vascular and inflammatory diseases in the posterior segment of the eye. In this study the gene (mRNA) expression of TLRs 1-10 was investigated using RT-PCR and comparative OCR and the protein expression and localisation of selected TLRs (3, 4, 6 and 9) were examined using western blotting, flow cytometry and immunofluorescent staining. PCR showed gene expression of TLR1-6 and 9 in human choroidal endothelial cells (hCEC) and TLR2-6, 9 and 10 in human retinal endothelial cells (hREC). Western blotting detected TLR3, 4 and 9 proteins in both hCEC and hREC with higher levels in hCEC, whilst TLR6 protein was not detectable in either endothelial cell type. Flow cytometry detected all four TLRs (3, 4, 6 and 9) on the cell surface and intracellularly, TLR6 expression was detectable but low. The expression and localisation of TLR3, 4 and 9 were confirmed by immunofluorescent staining in endothelial cells and whole tissue sections and their functionality tested by expression of IL-6 (ELISA) in response to stimulation with specific TLR ligands. This study has, for the first time, identified the differential expression and localisation of TLRs in intraocular endothelial cells. This profiling will help inform our understanding of different retinal and choroidal vascular diseases, as well as the development of future treatments for intraocular vascular diseases. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Stewart, Elizabeth A.; Wei, Ruoxin; Branch, Matthew J.; Sidney, Laura E.; Amoaku, Winfried M.] Univ Nottingham, Acad Ophthalmol, Div Clin Neurosci, Queens Med Ctr, Nottingham NG7 2UH, England.
C3 University of Nottingham
RP Amoaku, WM (通讯作者)，Univ Nottingham, Acad Ophthalmol, Div Clin Neurosci, Queens Med Ctr, B Floor,Eye & ENT Bldg, Nottingham NG7 2UH, England.
EM Elizabeth.stewart@nottingham.ac.uk; Roisin.wei@gmail.com;
   Matthew.Branch@nottingham.ac.uk; laura.sidney@nottingham.ac.uk;
   Winfried.amoaku@nottingham.ac.uk
RI Sidney, Laura/J-6254-2019; Branch, Matthew/AAE-9105-2019
OI Sidney, Laura/0000-0003-1466-7597; Amoaku, Winfried/0000-0001-5028-7984;
   Stewart, Elizabeth A/0000-0002-6248-4464; Branch, Matthew
   James/0000-0002-8734-0037
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NR 67
TC 27
Z9 28
U1 0
U2 12
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD SEP
PY 2015
VL 138
BP 114
EP 123
DI 10.1016/j.exer.2015.06.012
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CQ7IV
UT WOS:000360777100014
PM 26091789
DA 2022-11-30
ER

PT J
AU Ogawa, K
   Kuse, Y
   Tsuruma, K
   Kobayashi, S
   Shimazawa, M
   Hara, H
AF Ogawa, Kenjirou
   Kuse, Yoshiki
   Tsuruma, Kazuhiro
   Kobayashi, Saori
   Shimazawa, Masamitsu
   Hara, Hideaki
TI Protective effects of bilberry and lingonberry extracts against blue
   light-emitting diode light-induced retinal photoreceptor cell damage in
   vitro
SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Article
DE Anthocyanin; Bilberry; Blue LED light; Lingonberry; Proanthocyanidin;
   Resveratrol; Retinal photoreceptor
ID VACCINIUM-MYRTILLUS ANTHOCYANOSIDES; SINGLET OXYGEN; HYDROGEN-PEROXIDE;
   OXIDATIVE STRESS; EPITHELIAL-CELLS; APOPTOSIS; RESVERATROL; KINASE;
   VIVO; DEGENERATION
AB Background: Blue light is a high-energy or short-wavelength visible light, which induces retinal diseases such as age-related macular degeneration and retinitis pigmentosa. Bilberry (Vaccinium myrtillus L.) and lingonberry (Vaccinium vitis-idaea) contain high amounts of polyphenols (anthocyanins, resveratrol, and proanthocyanidins) and thus confer health benefits. This study aimed to determine the protective effects and mechanism of action of bilberry extract (B-ext) and lingonberry extract (L-ext) and their active components against blue light-emitting diode (LED) light-induced retinal photoreceptor cell damage.
   Methods: Cultured murine photoreceptor (661 W) cells were exposed to blue LED light following treatment with B-ext, L-ext, or their constituents (cyanidin, delphinidin, malvidin, trans-resveratrol, and procyanidin B2). 661 W cell viability was assessed using a tetrazolium salt (WST-8) assay and Hoechst 33342 nuclear staining, and intracellular reactive oxygen species (ROS) production was determined using CM-H(2)DCFDA after blue LED light exposure. Activation of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor-kappa B (NF-kappa B), and LC3, an ubiquitin-like protein that is necessary for the formation of autophagosomes, were analyzed using Western blotting. Caspase-3/7 activation caused by blue LED light exposure in 661 W cells was determined using a caspase-3/7 assay kit.
   Results: B-ext, L-ext, NAC, and their active components improved the viability of 661 W cells and inhibited the generation of intracellular ROS induced by blue LED light irradiation. Furthermore, B-ext and L-ext inhibited the activation of p38 MAPK and NF-kappa B induced by blue LED light exposure. Finally, B-ext, L-ext, and NAC inhibited caspase-3/7 activation and autophagy.
   Conclusions: These findings suggest that B-ext and L-ext containing high amounts of polyphenols exert protective effects against blue LED light-induced retinal photoreceptor cell damage mainly through inhibition of ROS production and activation of pro-apoptotic proteins.
C1 [Ogawa, Kenjirou; Kuse, Yoshiki; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Gifu 5011196, Japan.
   [Kobayashi, Saori] Wakasa Seikatsu Co Ltd, Shimogyo Ku, Kyoto 6008008, Japan.
C3 Gifu Pharmaceutical University
RP Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
EM hidehara@gifu-pu.ac.jp
RI Kuse, Yoshiki/AAB-7445-2021; Kobayashi, Saori/GXV-3835-2022
OI Hara, Hideaki/0000-0003-2046-9001
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NR 48
TC 51
Z9 52
U1 10
U2 76
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1472-6882
J9 BMC COMPLEM ALTERN M
JI BMC Complement. Altern. Med.
PD APR 2
PY 2014
VL 14
AR 120
DI 10.1186/1472-6882-14-120
PG 11
WC Integrative & Complementary Medicine
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Integrative & Complementary Medicine
GA AF1JP
UT WOS:000334470500001
PM 24690313
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Radu, RA
   Hu, J
   Jiang, ZC
   Bok, D
AF Radu, Roxana A.
   Hu, Jane
   Jiang, Zhichun
   Bok, Dean
TI Bisretinoid-mediated Complement Activation on Retinal Pigment Epithelial
   Cells Is Dependent on Complement Factor H Haplotype
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Complement System; Epithelium; Inflammation; Retinal Degeneration;
   Retinoid; Age-related Macular Degeneration (AMD); Bisretinoids;
   Complement Factor H (CFH); Recessive Stargardt Macular Degeneration
   (STGD1); Retinal Pigment Epithelium
ID MANNOSE-BINDING LECTIN; HUMAN RPE CELLS; MACULAR DEGENERATION;
   REGULATORY PROTEINS; LIPOFUSCIN FLUOROPHORE; STARGARDT DISEASE;
   OXIDATIVE STRESS; MOUSE MODEL; RISK; A2E
AB Background: AMD and STGD1 are blinding diseases with similar clinical presentations but unrelated genetic causes. Results: Bisretinoid-dependent complement reactivity on RPE cells involves the alternative pathway and depends on the CFH haplotype. Conclusion: Inefficient CFH synthesis because of either Y402H and I62V substitutions or bisretinoid accumulation predisposes RPE cells to disease. Significance: These results suggest a common inflammatory etiology for AMD and STGD1.
   Age-related macular degeneration (AMD) is a common central blinding disease of the elderly. Homozygosity for a sequence variant causing Y402H and I62V substitutions in the gene for complement factor H (CFH) is strongly associated with risk of AMD. CFH, secreted by many cell types, including those of the retinal pigment epithelium (RPE), is a regulatory protein that inhibits complement activation. Recessive Stargardt maculopathy is another central blinding disease caused by mutations in the gene for ABCA4, a transporter in photoreceptor outer segments (OS) that clears retinaldehyde and prevents formation of toxic bisretinoids. Photoreceptors daily shed their distal OS, which are phagocytosed by the RPE cells. Here, we investigated the relationship between the CFH haplotype of human RPE (hRPE) cells, exposure to OS containing bisretinoids, and complement activation. We show that hRPE cells of the AMD-predisposing CFH haplotype (HH402/VV62) are attacked by complement following exposure to bisretinoid-containing Abca4(-/-) OS. This activation was dependent on factor B, indicating involvement of the alternative pathway. In contrast, hRPE cells of the AMD-protective CFH haplotype (YY402/II62) showed no complement activation following exposure to either Abca4(-/-) or wild-type OS. The AMD-protective YY402/II62 hRPE cells were more resistant to the membrane attack complex, whereas HH402/VV62 hRPE cells showed significant membrane attack complex deposition following ingestion of Abca4(-/-) OS. These results suggest that bisretinoid accumulation in hRPE cells stimulates activation and dysregulation of complement. Cells with an intact complement negative regulatory system are protected from complement attack, whereas cells with reduced CFH synthesis because of the Y402H and I62V substitutions are vulnerable to disease.
C1 [Radu, Roxana A.; Hu, Jane; Jiang, Zhichun; Bok, Dean] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Bok, Dean] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
   [Bok, Dean] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles;
   University of California Los Angeles Medical Center; David Geffen School
   of Medicine at UCLA; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA; University of
   California System; University of California Los Angeles; University of
   California Los Angeles Medical Center; David Geffen School of Medicine
   at UCLA
RP Radu, RA (通讯作者)，Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, 100 Stein Plaza, Los Angeles, CA 90095 USA.
EM radu@jsei.ucla.edu
RI Radu, Roxana A./K-8924-2019
OI Radu, Roxana/0000-0002-5064-6403
FU Stein/Oppenheimer Endowment Award grant; National Eye Institute/Jules
   Stein Eye Institute [EY000331]; Macula Vision Research Foundation
   [20081840]; Arnold and Mabel Beckman Initiative for Macular Degeneration
   Award [1102]; NATIONAL EYE INSTITUTE [P30EY000331] Funding Source: NIH
   RePORTER
FX This work was supported by a Stein/Oppenheimer Endowment Award grant (to
   R. A. R.), by National Eye Institute/Jules Stein Eye Institute Core
   Grant EY000331 (to R. A. R. and D. B.), by Macula Vision Research
   Foundation Award 20081840 (to D. B.), and by Arnold and Mabel Beckman
   Initiative for Macular Degeneration Award 1102 (to D. B.).
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NR 49
TC 35
Z9 35
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 28
PY 2014
VL 289
IS 13
BP 9113
EP 9120
DI 10.1074/jbc.M114.548669
PG 8
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA AD7UJ
UT WOS:000333472100031
PM 24550392
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Slotnick, S
   Sherman, J
AF Slotnick, Samantha
   Sherman, Jerome
TI Panoramic Autofluorescence: Highlighting Retinal Pathology
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE fundus autofluorescence; Optos; panoramic; retinal imaging technology;
   retinal pathology; retinitis pigmentosa; spectral domain optical
   coherence tomography; SD-OCT; ultra-widefield
ID VIVO FUNDUS AUTOFLUORESCENCE; GEOGRAPHIC ATROPHY; PATTERNS
AB Purpose. Recent technological advances in fundus autofluorescence (FAF) are providing new opportunities for insight into retinal physiology and pathophysiology. FAF provides distinctly different imaging information than standard photography or color separation. A review of the basis for this imaging technology is included to help the clinician understand how to interpret FAF images. Cases are presented to illustrate image interpretation.
   Methods. Optos, which manufactures equipment for simultaneous panoramic imaging, has recently outfitted several units with AF capabilities. Six cases are presented in which panoramic autofluorescent (PAF) images highlight retinal pathology, using Optos' Ultra-Widefield technology. Supportive imaging technologies, such as Optomap (R) images and spectral domain optical coherence tomography (SD-OCT), are used to assist in the clinical interpretation of retinal pathology detected on PAF.
   Results. Hypofluorescent regions on FAF are identified to occur along with a disruption in the photoreceptors and/or retinal pigment epithelium, as borne out on SD-OCT. Hyperfluorescent regions on FAF occur at the advancing zones of retinal degeneration, indicating impending damage. PAF enables such inferences to be made in retinal areas which lie beyond the reach of SD-OCT imaging. PAF also enhances clinical pattern recognition over a large area and in comparison with the fellow eye. Symmetric retinal degenerations often occur with genetic conditions, such as retinitis pigmentosa, and may impel the clinician to recommend genetic testing.
   Conclusions. Autofluorescent ophthalmoscopy is a non-invasive procedure that can detect changes in metabolic activity at the retinal pigment epithelium before clinical ophthalmoscopy. Already, AF is being used as an adjunct technology to fluorescein angiography in cases of age-related macular degeneration. Both hyper- and hypoautofluorescent changes are indicative of pathology. Peripheral retinal abnormalities may precede central retinal impacts, potentially providing early signs for intervention before impacting visual acuity. The panoramic image enhances clinical pattern recognition over a large area and in comparison between eyes. Optos' Ultra-Widefield technology is capable of capturing high-resolution images of the peripheral retina without requiring dilation. (Optom Vis Sci 2012;89:E575-E584)
C1 [Slotnick, Samantha; Sherman, Jerome] SUNY Coll Optometry, New York, NY 10036 USA.
   [Slotnick, Samantha; Sherman, Jerome] SUNY, Inst Eye, New York, NY USA.
   [Sherman, Jerome] Ctr Laser, New York, NY USA.
C3 State University of New York (SUNY) System; SUNY Optometry; State
   University of New York (SUNY) System; SUNY Community College; SUNY
   Maritime College; SUNY Optometry
RP Slotnick, S (通讯作者)，SUNY Coll Optometry, 33 W 42nd St, New York, NY 10036 USA.
EM think202020@gmail.com
CR Bird AC, 2009, FUNDUS AUTOFLUORESCE, P70
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NR 29
TC 14
Z9 14
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-5488
EI 1538-9235
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD MAY
PY 2012
VL 89
IS 5
BP E575
EP E584
DI 10.1097/OPX.0b013e318250835d
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 937JM
UT WOS:000303654800003
PM 22446719
DA 2022-11-30
ER

PT J
AU Huang, H
   Shen, JK
   Vinores, SA
AF Huang, Hu
   Shen, Jikui
   Vinores, Stanley A.
TI Blockade of VEGFR1 and 2 Suppresses Pathological Angiogenesis and
   Vascular Leakage in the Eye
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; OXYGEN-INDUCED RETINOPATHY; CHOROIDAL
   NEOVASCULARIZATION; MACULAR DEGENERATION; PERMEABILITY FACTOR; TUMOR
   ANGIOGENESIS; MOUSE MODEL; EXPRESSION; HYPOXIA; INHIBITION
AB Objective: VEGFR1 and 2 signaling have both been increasingly shown to mediate complications of ischemic retinopathies, including retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and diabetic retinopathy (DR). This study evaluates the effects of blocking VEGFR1 and 2 on pathological angiogenesis and vascular leakage in ischemic retinopathy in a model of ROP and in choroidal neovascularization (CNV) in a model of AMD.
   Materials and Methods: Neutralizing antibodies specific for mouse VEGFR1 (MF1) and VEGFR2 (DC101) were administrated systemically. CNV was induced by laser photocoagulation and assessed 14d after laser treatment. Retinal NV was generated in oxygen-induced ischemic retinopathy (OIR) and assessed at p17. NV quantification was determined by measuring NV tufts and vascular leakage was quantified by measuring [H-3]-mannitol leakage from blood vessels into the retina. Gene expression was measured by real-time quantitative (Q) PCR.
   Results: VEGFR1 and VEGFR2 expressions were up-regulated during CNV pathogenesis. Both MF1 and DC101 significantly suppressed CNV at 50 mg/kg: DC101 suppressed CNV by 73 +/- 5% (p<0.0001) and MF1 by 64 +/- 6% (p = 0.0002) in a dosage-dependent manner. The combination of MF1 and DC101 enhanced the inhibitory efficacy and resulted in an accumulation of retinal microglia at the CNV lesion. Similarly, both MF1 and DC101 significantly suppressed retinal NV in OIR at 50 mg/kg: DC101 suppressed retinal NV by 54 +/- 8% (p = 0.013) and MF1 by 50 +/- 7% (p<0.0002). MF1 was even more effective at inhibiting ischemia-induced BRB breakdown than DC101: the retina/lung leakage ratio for MF1 was reduced by 73 +/- 24%, p = 0.001 and for DC101 by 12 +/- 4%, p = 0.003. The retina/renal leakage ratio for MF1 was reduced by 52 +/- 28%, p = 0.009 and for DC101 by 13 +/- 4%, p = 0.001.
   Conclusion: Our study provides further evidence that both VEGFR1 and 2 mediate pathological angiogenesis and vascular leakage in these models of ocular disease and suggests that antagonist antibodies to these receptor tyrosine kinases (RTKs) are potential therapeutic agents.
C1 [Huang, Hu; Shen, Jikui; Vinores, Stanley A.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Huang, H (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
EM svinores@jhmi.edu
FU National Eye Institute [EY017164]; Lilly/ImClone; Wilmer Eye Institute;
   NIH [P30EY1765]; NATIONAL EYE INSTITUTE [R01EY017164, P30EY001765]
   Funding Source: NIH RePORTER
FX The study was supported by NIH grant EY017164 from the National Eye
   Institute and a stipend from Lilly/ImClone (S. A. V.), The Louise L.
   Sloan Research Grant Award from Wilmer Eye Institute (H. H.), ARVO
   Travel Grant from the National Eye Institute (H. H.), and NIH core grant
   P30EY1765. The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.; The
   authors have the following competing interest. A stipend was received
   from Lilly/ImClone as part of a Sponsored Research Agreement to
   partially support this study. There are no patents, products in
   development or marketed products to declare. This does not alter the
   authors' adherence to all the PLoS ONE policies on sharing data and
   materials, as detailed online in the guide for authors.
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NR 67
TC 76
Z9 85
U1 1
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 22
PY 2011
VL 6
IS 6
AR e21411
DI 10.1371/journal.pone.0021411
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 782TF
UT WOS:000292033700080
PM 21731737
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Manjunath, V
   Shah, H
   Fujimoto, JG
   Duker, JS
AF Manjunath, Varsha
   Shah, Heeral
   Fujimoto, James G.
   Duker, Jay S.
TI Analysis of Peripapillary Atrophy Using Spectral Domain Optical
   Coherence Tomography
SO OPHTHALMOLOGY
LA English
DT Article
ID PARAPAPILLARY CHORIORETINAL ATROPHY; ANGLE-CLOSURE GLAUCOMA; HIGHLY
   MYOPIC EYES; HISTOMORPHOMETRY; DISC
AB Objective: To study retinal morphologic changes around the optic disc in patients with peripapillary atrophy (PPA) with high-resolution spectral domain optical coherence tomography (SD OCT).
   Design: Cross-sectional, retrospective analysis.
   Participants: A total of 103 eyes of 73 patients with PPA and 21 eyes of 12 normal patients seen at the New England Eye Center, Tufts Medical Center, between January 2007 and August 2009.
   Methods: Spectral domain optical coherence tomography images taken through the region of PPA were quantitatively and qualitatively analyzed. Inclusion criteria included eyes with at least 300 mu m of temporal PPA as detected on color fundus photographs. The study population was divided into subgroups according to the following clinical diagnoses: glaucoma (n=13), age-related macular degeneration (n=11), high myopia (n=11), glaucoma and high myopia (n=3), and optic neuropathy (n=11). Fifty-four patients were classified with other diagnoses. By using OCT software, retinal thickness and retinal nerve fiber layer (RNFL) thickness were both manually measured perpendicular to the internal limiting membrane and retinal pigment epithelium (RPE) 300 mu m temporal to the optic disc, within the region of PPA. Qualitative analysis for morphologic changes in the atrophic area was also performed.
   Main Outcome Measures: Qualitative assessment and quantitative measures of retinal and RNFL thickness in PPA.
   Results: The study group was categorized by 6 characteristics demonstrated in the area of PPA by SD OCT: RPE loss with accompanying photoreceptor loss, RPE disruption, RNFL thickening with plaque-like formation, intraretinal cystic changes, inner and outer retinal thinning, and abnormal retinal sloping. Statistical analysis of measurements revealed a statistically significant difference in the total retinal thickness between normal eyes and eyes with PPA (P=0.0005), with normal eyes 15% thicker than the eyes with PPA; however, the RNFL thickness was not significantly different between the normal eyes and the eyes with PPA (P=0.05).
   Conclusions: Eyes with PPA manifest characteristic retinal changes that can be described via SD OCT.
C1 [Duker, Jay S.] Tufts Med Ctr, Dept Ophthalmol, New England Eye Ctr, Boston, MA 02111 USA.
   [Fujimoto, James G.] MIT, Elect Res Lab, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
C3 Tufts Medical Center; Massachusetts Institute of Technology (MIT)
RP Duker, JS (通讯作者)，Tufts Med Ctr, Dept Ophthalmol, New England Eye Ctr, 800 Washington St,Box 450, Boston, MA 02111 USA.
EM JDuker@tuftsmedicalcenter.org
FU Research to Prevent Blindness Challenge; Tufts University School of
   Medicine; National Institutes of Health [R01-EY11289-24, R01-EY13178-10,
   R01-EY013516-07]; Air Force Office of Scientific Research
   [FA9550-07-1-0101, FA9550-07-1-0014]; Massachusetts Lions Eye Research
   Fund; NATIONAL EYE INSTITUTE [R01EY013516, R01EY011289, R01EY013178]
   Funding Source: NIH RePORTER
FX Supported in part by a Research to Prevent Blindness Challenge grant to
   the New England Eye Center/Department of Ophthalmology, Tufts University
   School of Medicine, National Institutes of Health contracts
   R01-EY11289-24, R01-EY13178-10, R01-EY013516-07, Air Force Office of
   Scientific Research FA9550-07-1-0101, FA9550-07-1-0014, and
   Massachusetts Lions Eye Research Fund. The sponsor or funding
   organization had no role in the design or conduct of this research.
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NR 18
TC 42
Z9 44
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAR
PY 2011
VL 118
IS 3
BP 531
EP 536
DI 10.1016/j.ophtha.2010.07.013
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 729QA
UT WOS:000287964400017
PM 20920826
OA Green Accepted, Green Submitted
DA 2022-11-30
ER

PT J
AU Parodi, MB
   Iacono, P
   Kontadakis, DS
   Zucchiatti, L
   Cascavilla, ML
   Bandello, F
AF Parodi, Maurizio Battaglia
   Iacono, Pierluigi
   Kontadakis, Dimitrios Stelyos
   Zucchiatti, Ilaria
   Cascavilla, Maria Lucia
   Bandello, Francesco
TI Bevacizumab vs Photodynamic Therapy for Choroidal Neovascularization in
   Multifocal Choroiditis
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID PUNCTATE INNER CHOROIDOPATHY; INTRAVITREAL BEVACIZUMAB; MACULAR
   DEGENERATION; SUBRETINAL FIBROSIS; PANUVEITIS; AVASTIN
AB Objective: To compare the effectiveness of photodynamic therapy (PDT) vs intravitreal bevacizumab injection in patients with subfoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis (MC).
   Methods: Patients affected by subfoveal CNV associated with MC referred for clinical evaluation from March 1, 2005, to July 31, 2008, were considered for this pilot randomized clinical trial. Twenty-seven patients were included in the study and followed up from March 15, 2005, through April 30, 2009. After randomization, patients receiving PDT were treated according to the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy protocol, whereas patients receiving intravitreal bevacizumab injection, after a loading phase of 3 monthly injections, were examined monthly and re-treated on the basis of detection of fluid on optical coherence tomography and/or leakage on fluorescein angiography.
   Main Outcome Measures: The primary outcome measure was the 5- and 15-letter change on the Early Treatment of Diabetic Retinopathy Study charts at 12-month examinations compared with baseline. Secondary outcomes included central macular thickness changes.
   Results: Thirteen and 14 patients were randomized to PDT and bevacizumab treatment, respectively. At the 12-month examination, 5 of 14 eyes treated with bevacizumab and 0 of 13 eyes treated with PDT experienced a best-corrected visual acuity gain of greater than 3 lines (P=.04). Twelve eyes in the bevacizumab group and 6 eyes in the PDT group gained more than 1 line (P=.04). The central macular thickness showed a progressive reduction in both subgroups without a significant difference compared with the baseline values.
   Conclusions: Greater beneficial effects can be achieved using intravitreal bevacizumab injection rather than PDT for the treatment of subfoveal CNV secondary to MC. Larger multicenter investigations are needed to confirm our preliminary results.
   Application to Clinical Practice: Currently, there is no precise indication regarding the best therapeutic approach to subfoveal CNV secondary to MC. This investigation was designed to verify whether intravitreal bevacizumab injection has a more beneficial effect with respect to PDT.
C1 [Iacono, Pierluigi] Fondaz GB Bietti Oftalmol, Ist Ricovero & Cura Carattere Sci, Rome, Italy.
   [Parodi, Maurizio Battaglia; Iacono, Pierluigi; Kontadakis, Dimitrios Stelyos; Zucchiatti, Ilaria; Cascavilla, Maria Lucia; Bandello, Francesco] Univ Vita Salute, San Raffaele Sci Inst, Dept Ophthalmol, I-20132 Milan, Italy.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele
RP Iacono, P (通讯作者)，Fondaz GB Bietti Oftalmol, Ist Ricovero & Cura Carattere Sci, Rome, Italy.
EM pierluigi.iacono@libero.it
RI Iacono, Pierluigi/AAD-3158-2020; bandello, francesco/AAH-2405-2019;
   Parodi, Maurizio Battaglia/K-7876-2016; Zucchiatti, Ilaria/ABA-7083-2020
OI bandello, francesco/0000-0003-3238-9682; Battaglia Parodi,
   Maurizio/0000-0002-0385-7961; Cascavilla, Maria
   Lucia/0000-0002-6344-5512
CR Avery RL, 2006, OPHTHALMOLOGY, V113, P363, DOI 10.1016/j.ophtha.2005.11.019
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NR 26
TC 24
Z9 26
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0003-9950
EI 1538-3601
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD SEP
PY 2010
VL 128
IS 9
BP 1100
EP 1103
DI 10.1001/archophthalmol.2010.205
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 649JI
UT WOS:000281764500001
PM 20837791
DA 2022-11-30
ER

PT J
AU Khurana, RN
   Dupas, B
   Bressler, NM
AF Khurana, Rahul N.
   Dupas, Benedicte
   Bressler, Neil M.
TI Agreement of Time-Domain and Spectral-Domain Optical Coherence
   Tomography with Fluorescein Leakage from Choroidal Neovascularization
SO OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; RANIBIZUMAB; VERTEPORFIN;
   GUIDELINES
AB Purpose: To compare fluorescein leakage from choroidal neovascularization (CNV) with signs of intraretinal or subretinal fluid on time-domain optical coherence tomography (TD-OCT) and spectral-domain optical coherence tomography (SD-OCT) in patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy for CNV caused by age-related macular degeneration (AMD).
   Design: Retrospective, consecutive case series.
   Participants: Fifty-nine eyes of 56 patients with neovascular AMD receiving anti-VEGF therapy.
   Methods: All patients were imaged with fluorescein angiography (FA), TD-OCT (Stratus, Carl Zeiss Meditec, Inc., Dublin, CA), and SD-OCT (Cirrus, Carl Zeiss Meditec, Inc). All images were analyzed by an experienced reading center grader masked to all clinical data. Fluorescein leakage from CNV and OCT abnormalities (presence of interstitial fluid, retinal cystoid abnormalities, and subretinal fluid) were documented for each visit.
   Main Outcome Measures: Agreement of OCT findings with presence or absence of fluorescein leakage from CNV.
   Results: For TD-OCT, the sensitivity, specificity, positive predictive value, and negative predicative value (and 95% confidence intervals) for OCT abnormalities were 59% (46-72), 63% (50-75%), 61% (49-73), and 61% (48-74), respectively. For SD-OCT, the sensitivity, specificity, positive predictive value, and negative predictive value (and 95% confidence intervals) for OCT abnormalities were 90% (82-98), 47% (34-60), 62% (49-75), and 82% (72-92), respectively.
   Conclusions: Spectral-domain optical coherence tomography seems more likely than TD-OCT to detect abnormalities when fluorescein leakage from CNV is detected after anti-VEGF therapy. However, SD-OCT also seems to detect abnormalities frequently in the absence of fluorescein leakage from CNV. Whether treatment decisions based on any of these modalities result in visual acuity outcomes that are similar or superior to monthly treatments without such evaluations is unknown, but this study provides information that may assist in the design of studies to evaluate the role of OCT and FA in the management of CNV.
   Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2010; 117: 1376-1380 (C) 2010 by the American Academy of Ophthalmology.
C1 [Khurana, Rahul N.; Dupas, Benedicte; Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Retina Div,Johns Hopkins Med Inst, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Bressler, NM (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Retina Div,Johns Hopkins Med Inst, 600 N Wolfe St,Maumenee 752, Baltimore, MD 21287 USA.
EM nmboffice@jhmi.edu
RI Lockyer, Lori/C-7180-2018; Bennett, Sue/I-4643-2012
OI Lockyer, Lori/0000-0003-1517-2342; Bennett, Sue/0000-0001-9607-6285;
   Khurana, Rahul/0000-0001-5198-1353
FU Carl Zeiss Meditec; JHU; Ronald G. Michels Foundation; Fondation Odette
   et Jean Duranton de Magny, Fondation de France; Wilmer Retina Division
   Research Fund
FX NMB's employer, the Johns Hopkins University (JHU), but not NMB,
   receives funding from Carl Zeiss Meditec for sponsored projects by the
   Department of Ophthalmology for the efforts of NMB. NMB receives salary
   support for these sponsored projects; the terms of these projects are
   negotiated and administered by JHU's Office of Research Administration.
   Under JHU's policy, support for the costs of research, administered by
   the institution, does not constitute a conflict of interest.; Support:
   RNK is a Ronald G. Michels Fellow and supported by the Ronald G. Michels
   Foundation. Benedicte Dupas is supported by the Fondation Odette et Jean
   Duranton de Magny, Fondation de France. Also supported by the James P.
   Gills Professorship (Dr. Bressler) and a Wilmer Retina Division Research
   Fund.
CR Barbazetto I, 2003, ARCH OPHTHALMOL-CHIC, V121, P1253
   Brown DM, 2006, NEW ENGL J MED, V355, P1432, DOI 10.1056/NEJMoa062655
   Cohen SY, 2009, AM J OPHTHALMOL, V148, P409, DOI 10.1016/j.ajo.2009.04.001
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NR 11
TC 56
Z9 56
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2010
VL 117
IS 7
BP 1376
EP 1380
DI 10.1016/j.ophtha.2009.11.039
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 619NF
UT WOS:000279436200014
PM 20452027
DA 2022-11-30
ER

PT J
AU Boon, CJF
   Klevering, BJ
   Cremers, FPM
   Zonneveld-Vrieling, MN
   Theelen, T
   Den Hollander, AI
   Hoyng, CB
AF Boon, Camiel J. F.
   Klevering, B. Jeroen
   Cremers, Frans P. M.
   Zonneveld-Vrieling, Marijke N.
   Theelen, Thomas
   Den Hollander, Anneke I.
   Hoyng, Carel B.
TI Central Areolar Choroidal Dystrophy
SO OPHTHALMOLOGY
LA English
DT Article
ID CONE-ROD DYSTROPHY; PERIPHERIN/RDS GENE; MACULAR DEGENERATION; RETINAL
   DEGENERATION; FUNDUS AUTOFLUORESCENCE; R172W MUTATION; RDS GENE;
   RETINITIS-PIGMENTOSA; PHENOTYPIC VARIATION; ARG195LEU MUTATION
AB Objective: To describe the clinical characteristics, follow-up data and molecular genetic background in a large group of patients with central areolar choroidal dystrophy (CACD).
   Design: Retrospective case series study.
   Participants: One hundred three patients with CACD from the Netherlands.
   Methods: Ophthalmologic examination, including color vision testing, fundus photography, fluorescein angiography, fundus autofluorescence (FAF) imaging, optical coherence tomography, full-field electroretinography (ERG), multifocal ERG, and electrooculography. Blood samples were obtained for DNA extraction and subsequent analysis of the peripherin/RDS gene, as well as haplotype analysis.
   Main Outcome Measures: Clinical characteristics, phenotypic range, clinical follow-up data, and FAF findings.
   Results: The mean age at onset of visual loss was 46 years, with subsequent gradual deterioration in visual acuity. Ninety-eight patients carried a p.Arg142Trp mutation in peripherin/RDS, whereas 5 affected members of a CACD family carried a p.Arg172Gln peripherin/RDS mutation. A remarkable variation in disease severity was observed, and nonpenetrance was seen up to the age of 64 years, in up to 21% of mutation carriers. However, most macular lesions in mutation carriers displayed a typical stage of CACD. Substantial changes were seen on FAF imaging after a mean follow-up period of 11 months. Electrophysiologic data were consistent with a central cone dystrophy. The age at onset and phenotypic characteristics of CACD show considerable overlap with atrophic age-related macular degeneration (AMD). The great majority of p.Arg142Trp-carrying CACD patients originated from the southeast region of the Netherlands, and haplotype analysis strongly suggested a common founder mutation.
   Conclusions: When caused by a p.Arg142Trp mutation in the peripherin/RDS gene, CACD causes a central cone dystrophy phenotype. This mutation, which most likely originates from a common founder in most patients, is associated with a significant degree of nonpenetrance. In the elderly patient, CACD may be confused with AMD, especially in cases with decreased penetrance.
   Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:771-782 (C) 2009 by the American Academy of Ophthalmology.
C1 [Boon, Camiel J. F.; Klevering, B. Jeroen; Theelen, Thomas; Hoyng, Carel B.] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands.
   [Cremers, Frans P. M.; Den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.
   [Cremers, Frans P. M.; Zonneveld-Vrieling, Marijke N.; Den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands.
C3 Radboud University Nijmegen; Radboud University Nijmegen; Radboud
   University Nijmegen
RP Hoyng, CB (通讯作者)，Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM c.hoyng@ohk.umcn.nl
RI Theelen, Thomas/A-3192-2012; Klevering, B.J./L-4434-2015; Hollander,
   Anneke den/N-4911-2014; Cremers, Frans/A-5625-2014; Hoyng,
   C.B./H-8050-2014; Boon, Camiel/P-7534-2014
OI Theelen, Thomas/0000-0001-9067-1171; Cremers, Frans/0000-0002-4954-5592;
   Boon, Camiel/0000-0002-6737-7932
FU Gelderse Blindenstichting; Landelijke Stichting voor Blinden en
   Slechtzienden; Rotterdamse Vereniging Blindenbelangen; Stichting
   Blindenhulp; Stichting Ondersteuning Oogheelkunde's-Gravenhage;
   Stichting voor Ooglijders
FX Supported by the Gelderse Blindenstichting, the Landelijke Stichting
   voor Blinden en Slechtzienden, the Rotterdamse Vereniging
   Blindenbelangen, the Stichting Blindenhulp, the Stichting Ondersteuning
   Oogheelkunde's-Gravenhage, and the Stichting voor Ooglijders. The
   funding organizations had no role in the design or conduct of this
   research.
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NR 52
TC 66
Z9 66
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD APR
PY 2009
VL 116
IS 4
BP 771
EP 782
DI 10.1016/j.ophtha.2008.12.019
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 427YI
UT WOS:000264814600024
PM 19243827
DA 2022-11-30
ER

PT J
AU Semkova, I
   Fauser, S
   Lappas, A
   Smyth, N
   Kociok, N
   Kirchhof, B
   Paulsson, M
   Poulaki, V
   Joussen, AM
AF Semkova, Irina
   Fauser, Sascha
   Lappas, Alexandra
   Smyth, Neil
   Kociok, Norbert
   Kirchhof, Bernd
   Paulsson, Mats
   Poulaki, Vassiliki
   Joussen, Antonia M.
TI Overexpression of FasL in retinal pigment epithelial cells reduces
   choroidal neovascularization
SO FASEB JOURNAL
LA English
DT Article
DE choroidal neovascularization; apoptosis; inflammation
ID ENDOTHELIAL GROWTH-FACTOR; DISCIFORM MACULAR DEGENERATION; SUBRETINAL
   NEOVASCULARIZATION; TARGETED DISRUPTION; IMMUNE PRIVILEGE; APOPTOSIS;
   LIGAND; MEMBRANES; EXPRESSION; RETINOPATHY
AB Choroidal neovascularization (CNV) is responsible for the severe visual loss in age-related macular degeneration. CNV formation is considered to be due to an imbalance between pro-and antiangiogenic factors that lead to neovascular growth from the choriocapillaris into the subretinal space. To define whether FasL overexpression in retinal pigment epithelial cells (RPE) can inhibit choroidal neovascularization through Fas-FasL-mediated apoptosis, we examined the role of this pathway in a mouse model of laser-induced choroidal neovascularization. FasL was expressed in the retinal pigment epithelium of transgenic mice. Polymerase chain reaction (PCR), immunoblot, and immunohistochemistry confirmed that the transgene FasL was specifically expressed in RPE. The established laser model was used to induce choroidal neovascularization (CNV) in wild-type (WT) and transgenic mice. CNV formation was compared with respect to fluorescein angiographic leakage (at days 0 and 14 after laser injury) and histological appearance. The lesions were assessed on RPE-choroidal flatmounts after CD31-labeling and with confocal microscopy after perfusion with rhodamine-labeled concanavalin A (Con A). Apoptosis was quantified by TUNEL positivity and caspase activation. FasL mRNA and protein were highly expressed in the RPE of the transgenic mice before and after laser photocoagulation. In contrast, FasL was only weakly expressed in the RPE layer of WT C57BL/ 6J mice. While ruptures of Bruch's membrane and CNV formation were observed histologically two weeks after laser photocoagulation in transgenic as well as control eyes, the shape and size of CNV lesions were reduced in the transgenic mice. The area of leakage was decreased by 70% in FasL transgenic mice compared with WT mice (P < 0.005). The number of TUNEL-positive cells was greater in FasL-overexpressing mice and correlated with the expression of activated caspases. Th expression of other antiangiogenic factors such as PEDF remained unchanged. The specific overexpression of FasL in RPE layer reduced CNV formation in our laser model. Our results strongly point to the FasL-Fas pathway as a potential therapeutic target in controlling pathological choroidal neovascularization.
C1 Univ Cologne, Dept Vitreoretinal Surg, Ctr Ophthalmol, D-50931 Cologne, Germany.
   Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany.
   Univ Southampton, Ctr Biochem, Southampton, Hants, England.
   Univ Southampton, Sch Biol Sci, Southampton, Hants, England.
   Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
C3 University of Cologne; University of Cologne; University of Southampton;
   University of Southampton; Harvard University; Harvard Medical School;
   Massachusetts Eye & Ear Infirmary
RP Joussen, AM (通讯作者)，Univ Cologne, Dept Vitreoretinal Surg, Ctr Ophthalmol, Joseph Stelzmannstr 9, D-50931 Cologne, Germany.
EM joussena@googlemail.com
RI Joussen, Antonia/AAA-6901-2022
OI Smyth, Neil/0000-0002-3734-2149
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NR 63
TC 33
Z9 38
U1 0
U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD AUG
PY 2006
VL 20
IS 10
BP 1689
EP +
DI 10.1096/fj.05-5653fje
PG 13
WC Biochemistry & Molecular Biology; Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA 080RV
UT WOS:000240266600016
PM 16807368
DA 2022-11-30
ER

PT J
AU Bellmann, C
   Rubin, GS
   Kabanarou, SA
   Bird, AC
   Fitzke, FW
AF Bellmann, C
   Rubin, GS
   Kabanarou, SA
   Bird, AC
   Fitzke, FW
TI Fundus autofluorescence imaging compared with different confocal
   scanning laser ophthalmoscopes
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; IN-VIVO; GEOGRAPHIC ATROPHY; LIPOFUSCIN;
   RPE; FLUORESCENCE; ACCUMULATION; TOPOGRAPHY; MELANIN; LESIONS
AB Background: With the advent of confocal scanning laser ophthalmoscopes (cSLO), fundus autofluorescence (FAF) resulting mainly from lipofuscin accumulation on the level of the retinal pigment epithelium can be visualised in vivo. Various cSLOs are available to document FAF. The authors analysed and compared results of FAF using three different instruments.
   Methods: Eight eyes of eight normal volunteers and 18 eyes of 12 patients with different retinal diseases (age related macular degeneration, macular dystrophy, central serous retinopathy) were examined. FAF images were recorded from each subject with the Heidelberg retina angiograph (HRA), the Rodenstock cSLO (RcSLO) and the Zeiss Prototype SM 30-4024 (ZcSLO). For excitation an argon laser (488 nm) was used ( barrier filter: HRA 500 nm; RcSLO 515 nm; ZcSLO 521 nm). 32 FAF images were aligned and averaged using the same software for all cSLOs. FAF distribution was measured and grey scale values as well as root mean square (RMS) contrast were compared.
   Results: Mean age of all subjects was 55.5 (SD 21.4) years. The maximum grey scale value averaged across all eyes was 76.19 (39.34) for the HRA, 61.44 (22.12) for the ZcSLO and 37.0 (9.97) for the RcSLO. The RMS contrast was 0.46 (0.20) for the ZcSLO, 0.40 (0.12) for the HRA, and 0.13 (0.05) for the RcSLO. The differences between the cSLOs were statistically significant with higher grey scale levels and more contrast for the HRA and ZcSLO than the RcSLO (repeated measures ANOVA; p<0.0001). The differences between the HRA and the ZcSLO were not significant (post hoc comparisons; p<0.05).
   Conclusions: All cSLOs allow clinically useful FAF imaging in retinal diseases. However, grey scale levels and contrast were much lower on the RcSLO. Therefore, RcSLO images appear much darker than HRA or ZcSLO images. Furthermore, not all cSLOs have a fixed photodetector gain and a standardised value for the argon laser amplification, which is mandatory for an absolute comparison of FAF imaging results.
C1 UCL, Inst Ophthalmol, Dept Visual Sci, London EC1V 9EL, England.
   Moorfields Eye Hosp, London, England.
C3 University of London; University College London; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust
RP Fitzke, FW (通讯作者)，UCL, Inst Ophthalmol, Dept Visual Sci, 11-43 Bath St, London EC1V 9EL, England.
EM f.fitzke@ucl.ac.uk
RI Cerviño, Alejandro/L-5853-2014; Fitzke, Fred/C-3535-2008
OI Cerviño, Alejandro/0000-0001-8014-3279; 
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NR 31
TC 44
Z9 53
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD NOV
PY 2003
VL 87
IS 11
BP 1381
EP 1386
DI 10.1136/bjo.87.11.1381
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 741UP
UT WOS:000186479000018
PM 14609839
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Huang, Y
   Zhou, R
   Sun, ZH
   Zheng, YH
   Lin, B
AF Huang, Ying
   Zhou, Rong
   Sun, Zuhua
   Zheng, Yihan
   Lin, Bing
TI Vascular endothelial growth factor-A level in human breast milk after
   intravitreal injection of ranibizumab: a case report
SO INTERNATIONAL BREASTFEEDING JOURNAL
LA English
DT Article
DE Vascular endothelial growth factor-a; Human breast milk; Intravitreal
   injection; Ranibizumab
ID FACTOR VEGF; BEVACIZUMAB; RECEPTORS
AB Background Ranibizumab is one of intravitreal anti-vascular endothelial growth factor agents. It is applied in the treatments of choroidal neovascularization, age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion. Preliminary evidence suggests that intravitreal ranibizumab may enter the plasma and human breast milk in very low-level concentration. As a precaution, breastfeeding is not recommended during the treatment of intravitreal injection of ranibizumab. There are limited data regarding the change of anti-vascular endothelial growth factor concentration in human breast milk after intravitreal injection of ranibizumab, especially in the first 24 h after injection. The purpose of this report is to analyse the concentration change of vascular endothelial growth factor-A in human breast milk with time, in the short term after intravitreal injection of ranibizumab. Case presentation In June 2018, a 30-year-old patient breastfeeding a six-month-old baby was diagnosed with choroidal neovascularization of left eye in Eye Hospital of Wenzhou Medical University. She received four administrations of 0.5 mg intravitreal injection of ranibizumab of the left eye, and breast milk was collected just before the injection, and 1-3, 6, 12, 24, 48, and 72 h after intravitreal injection, and assessed for vascular endothelial growth factor-A concentration. The change in vascular endothelial growth factor-A concentration in human breast milk showed the same trend after each injection, decreasing significantly within 6-12 h (about 20-30% lower), and increasing to pre-injection level by 24 h after injection. Conclusions The concentration of vascular endothelial growth factor-A in human breast milk of a mother who continues lactating dropped initially and rose to pre-injection level about 24 h after intravitreal injection of ranibizumab. The data may offer more information to evaluate the impact of anti-vascular endothelial growth factor agent intravitreal injection of lactating mothers and their breastfed infants.
C1 [Lin, Bing] Wenzhou Med Univ, Eye Hosp, Wenzhou, Zhejiang, Peoples R China.
   Wenzhou Med Univ, Sch Ophthalmol & Optometry, Wenzhou, Zhejiang, Peoples R China.
C3 Wenzhou Medical University; Wenzhou Medical University
RP Lin, B (通讯作者)，Wenzhou Med Univ, Eye Hosp, Wenzhou, Zhejiang, Peoples R China.
EM lbing124@126.com
FU Zhejiang Provincial Natural Science Foundation of China [LY17H120006]
FX Zhejiang Provincial Natural Science Foundation of China (LY17H120006).
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NR 16
TC 0
Z9 0
U1 0
U2 0
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1746-4358
J9 INT BREASTFEED J
JI Int. Breastfeed. J.
PD MAR 31
PY 2022
VL 17
IS 1
AR 25
DI 10.1186/s13006-022-00463-y
PG 5
WC Obstetrics & Gynecology; Pediatrics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Obstetrics & Gynecology; Pediatrics
GA 0E9VF
UT WOS:000777019000001
PM 35361227
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kim, YK
   Hong, HK
   Yoo, HS
   Park, SP
   Park, KH
AF Kim, Yong-Kyu
   Hong, Hye Kyoung
   Yoo, Hyo Soon
   Park, Sung Pyo
   Park, Kyu Hyung
TI AICAR upregulates ABCA1/ABCG1 expression in the retinal pigment
   epithelium and reduces Bruch's membrane lipid deposit in ApoE deficient
   mice
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE AICA ribonucleotide; AMP-Activated protein kinases; ATP-Binding cassette
   transporters; Cholesterol; Macular degeneration; Retinal pigment
   epithelium
ID ACTIVATED PROTEIN-KINASE; CHOLESTEROL EFFLUX; APOLIPOPROTEIN-E; MACULAR
   DEGENERATION; GENETIC-VARIANTS; AGE; ASSOCIATION; AMPK; ATHEROSCLEROSIS;
   MACROPHAGES
AB The etiology of age-related macular degeneration (AMD) is diverse; however, recent evidence suggests that the lipid metabolism-cholesterol pathway might be associated with the pathophysiology of AMD. The ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1, are essential for the formation of high-density lipoprotein (HDL) and the regulation of macrophage cholesterol efflux. The failure of retinal or retinal pigment epithelium (RPE) cholesterol efflux to remove excess intracellular lipids causes morphological and functional damage to the retina. In this study, we investigated whether treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMP-activated protein kinase (AMPK) activator, improves RPE cholesterol efflux and Bruch's membrane (BM) lipid deposits. The protein and mRNA levels of ABCA1 and ABCG1 in ARPE-19 cells and retinal and RPE/choroid tissue from apolipoprotein E-deficient (ApoE(-/-)) mice were evaluated after 24 weeks of AICAR treatment. The cholesterol efflux capacity of ARPE-19 cells and the cholesterol-accepting capacity of apoB-depleted serum from mice were measured. The thickness of the BM and the degree of lipid deposition were evaluated using electron microscopy. AICAR treatment increased the phosphorylation of AMPK and the protein and mRNA expression of ABCA1 and ABCG1 in vitro. It promoted cholesterol efflux from ARPE-19 cells and upregulated the protein and mRNA levels of ABCA1 and ABCG1 in the retina and RPE in vivo. ApoB-depleted serum from the AICAR-treated group showed enhanced cholesterol-accepting capacity. Long-term treatment with AICAR reduced BM thickening and lipid deposition in ApoE(-/-) mice. In conclusion, AICAR treatment increased the expression of lipid transporters in the retina and RPE in vivo, facilitated intracellular cholesterol efflux from the RPE in vitro, and improved the functionality of HDL to accept cholesterol effluxed from the cell, possibly via AMPK activation. Collectively, these effects might contribute to the improvement of early age-related pathologic changes in the BM. Pharmacological improvement of RPE cholesterol efflux via AMPK activation may be a potential treatment strategy for AMD.
C1 [Kim, Yong-Kyu; Park, Sung Pyo] Hallym Univ, Kangdong Sacred Heart Hosp, Dept Ophthalmol, Coll Med, Seongan Ro 150, Seoul 05355, South Korea.
   [Hong, Hye Kyoung; Park, Kyu Hyung] Seoul Natl Univ, Dept Ophthalmol, Bundang Hosp, Seongnam, South Korea.
   [Yoo, Hyo Soon] Seoul Natl Univ, Bundang Hosp, Dept Otorhinolaryngol Head & Neck Surg, Seoul, South Korea.
   [Yoo, Hyo Soon] Seoul Natl Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, Seoul, South Korea.
   [Park, Kyu Hyung] Seoul Natl Univ, Dept Ophthalmol, Coll Med, Seoul, South Korea.
C3 Hallym University; Seoul National University (SNU); Seoul National
   University (SNU); Seoul National University Hospital; Seoul National
   University (SNU); Seoul National University Hospital; Seoul National
   University (SNU)
RP Park, SP (通讯作者)，Hallym Univ, Kangdong Sacred Heart Hosp, Dept Ophthalmol, Coll Med, Seongan Ro 150, Seoul 05355, South Korea.; Park, KH (通讯作者)，Seoul Natl Univ, Bundang Hosp, Dept Ophthalmol, Coll Med, 82,Gumi Ro 173 Beon Gil, Seongnam Si 13620, Gyeonggi Do, South Korea.
EM eyepyo@gmail.com; jiani4@snu.ac.kr
FU Korean Association of Retinal Degeneration; SK Telecom Research Fund
   [06-2014-160]; Basic Science Research Program through the National
   Research Foundation of Korea (NRF) - Ministry of Science and ICT
   [2018R1A2B6007809, 2021R1F1A1057121]
FX This research was supported by the Korean Association of Retinal
   Degeneration, the SK Telecom Research Fund [grant number 06-2014-160] ,
   and the Basic Science Research Program through the National Research
   Foundation of Korea (NRF) funded by the Ministry of Science and ICT
   [grant numbers 2018R1A2B6007809, 2021R1F1A1057121] . The funding
   organization had no role in the design or conduct of this study.
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NR 49
TC 0
Z9 0
U1 2
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD DEC
PY 2021
VL 213
AR 108854
DI 10.1016/j.exer.2021.108854
EA NOV 2021
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA XE9QC
UT WOS:000723715300004
PM 34808137
DA 2022-11-30
ER

PT J
AU Zhang, H
   Su, BN
   Jiao, LY
   Xu, ZH
   Zhang, CJ
   Nie, JF
   Gao, ML
   Zhang, YV
   Jin, ZB
AF Zhang, Hang
   Su, Bingnan
   Jiao, Luyan
   Xu, Ze-Hua
   Zhang, Chang-Jun
   Nie, Jinfu
   Gao, Mei-Ling
   Zhang, Ying, V
   Jin, Zi-Bing
TI Transplantation of GMP-grade human iPSC-derived retinal pigment
   epithelial cells in rodent model: the first pre-clinical study for
   safety and efficacy in China
SO ANNALS OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE GMP grade; human iPSCs; RPE cells; pre-clinical study; transplantation;
   tumorigenicity
AB Background: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly due in large part to age-dependent atrophy of retinal pigment epithelium (RPE) cells. RPE cells form a monolayer located between the choroid and the outer segments of photoreceptors, playing multifarious roles in maintenance of visual function. Allogeneically induced pluripotent stem cell-derived RPE (iPSC-RPE or iRPE) has become a potential approach for providing an abundant source of donors for clinical cell products. Transplantation of iRPE has been proven effective in rescuing impaired retinas in Royal College of Surgeons (RCS) rats after approximately 5 to 6 weeks. Here, we explore the long-term (19 weeks) safety and efficacy of human iRPE cell transplantation in pre-clinical animal models.
   Methods: The expression of human RPE-specific markers in iRPE cells was determined using immunofluorescence staining. For the proliferative test, Ki-67 expression was also verified by immunofluorescence and flow cytometric analysis. Then, iRPE cells were transplanted into the subretinal space of immune-deficient NOD/SCID/IL-2Rgc(null) (NSG) mice to assess their safety. To evaluate whether the transplanted cells could survive and rescue visual function, we performed color fundus photography, focal electroretinogram and immunostaining after delivering iRPE cells into the subretinal space of RCS rats.
   Results: Human iRPE cells expressed native RPE-specific markers, such as microphthalmia-associated transcription factor (MiTF), retinal pigment epithelium-specific 65-kDa protein (RPE65) and tight-junction associated structural protein ( ZO-1), and their proliferative capacity (Ki-67 expression) was poor after 25 days of induction. A tumorigenicity test revealed no tumor formation or abnormal proliferation in the immunodeficient mice after subretinal injection of 5x10(5) iRPE cells. The transplanted iRPE cells survived for at least 19 weeks and maintained visual function for 15 weeks.
   Conclusions: In the present study, we provided further evidence for the use of human iRPE transplantation to treat retinal degenerative disease in pre-clinical animal models. Therefore, we consider human iRPE cells a promising source of cell replacement therapy for AMD.
C1 [Zhang, Hang; Su, Bingnan; Jin, Zi-Bing] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Inst Ophthalmol,Beijing Ophthalmol & Visu, Beijing, Peoples R China.
   [Zhang, Hang; Xu, Ze-Hua; Zhang, Chang-Jun; Gao, Mei-Ling] Wenzhou Med Univ, Eye Hosp, Inst Stem Cell Res, Lab Stem Cell & Retinal Regenerat, Wenzhou, Peoples R China.
   [Jiao, Luyan; Zhang, Ying, V] Nuwacell Biotechnol Co Ltd, Hefei, Peoples R China.
   [Nie, Jinfu] Chinese Acad Sci, Ctr Med Phys & Technol, Hefei Inst Phys Sci, Hefei, Peoples R China.
   [Jin, Zi-Bing] Wenzhou Med Univ, Natl Ctr Int Res Regenerat Med & Neurogenet, Wenzhou, Peoples R China.
C3 Capital Medical University; Wenzhou Medical University; Chinese Academy
   of Sciences; Hefei Institutes of Physical Science, CAS; Wenzhou Medical
   University
RP Jin, ZB (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Inst Ophthalmol,Beijing Ophthalmol & Visu, Beijing, Peoples R China.; Gao, ML (通讯作者)，Wenzhou Med Univ, Eye Hosp, Inst Stem Cell Res, Lab Stem Cell & Retinal Regenerat, Wenzhou, Peoples R China.; Zhang, YV (通讯作者)，Nuwacell Biotechnol Co Ltd, Hefei, Peoples R China.
EM gaoml@wmu.edu.cn; yzhang@nuwacell.com; jinzibing@foxmail.com
RI Jin, Zi-Bing/AAE-4106-2019; Gao, Mei-Ling/GNH-5156-2022
OI Jin, Zi-Bing/0000-0003-0515-698X; 
FU Beijing Natural Science Foundation [Z200014]; National Key R&D Program
   of China [2017YFA0105300]
FX This study was partly supported by the Beijing Natural Science
   Foundation (Z200014) and National Key R&D Program of China
   (2017YFA0105300).
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NR 56
TC 5
Z9 5
U1 3
U2 8
PU AME PUBL CO
PI SHATIN
PA FLAT-RM C 16F, KINGS WING PLAZA 1, NO 3 KWAN ST, SHATIN, HONG KONG
   00000, PEOPLES R CHINA
SN 2305-5839
EI 2305-5847
J9 ANN TRANSL MED
JI ANN. TRANSL. MED.
PD FEB
PY 2021
VL 9
IS 3
AR 245
DI 10.21037/atm-20-4707
PG 17
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA RP8FQ
UT WOS:000641959400032
PM 33708872
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Jiao, HH
   Provis, JM
   Natoli, R
   Rutar, M
AF Jiao, Haihan
   Provis, Jan M.
   Natoli, Riccardo
   Rutar, Matt
TI Ablation of C3 modulates macrophage reactivity in the outer retina
   during photo-oxidative damage
SO MOLECULAR VISION
LA English
DT Article
ID MICROGLIAL ACTIVATION; COMPLEMENT ACTIVATION; MACULAR DEGENERATION;
   PHAGOCYTOSIS; SYSTEM; MODEL; INFLAMMATION; DEPOSITION; OBESITY; STRESS
AB Purpose: Dysregulation of the complement cascade contributes to a variety of retinal dystrophies, including age-related macular degeneration (AMD). The central component of complement, C3, is expressed in abundance by macrophages in the outer retina, and its ablation suppresses photoreceptor death in experimental photo-oxidative damage. Whether this also influences macrophage reactivity in this model system, however, is unknown. We investigate the effect of C3 ablation on macrophage activity and phagocytosis by outer retinal macrophages during photo-oxidative damage.
   Methods: Age-matched C3 knockout (KO) mice and wild-type (WT) C57/B16 mice were subjected to photo-oxidative damage. Measurements of the outer nuclear layer (ONL) thickness and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess pathology and photoreceptor apoptosis, respectively. Macrophage abundance and phagocytosis were assessed with immunolabeling for pan-macrophage and phagocytic markers, in conjunction with TUNEL staining in cohorts of C3 KO and WT mice.
   Results: The C3 KO mice exhibited protection against photoreceptor cell death following photo-oxidative damage, which was associated with a reduction in immunoreactivity for the stress-related factor GFAP. In conjunction, there was a reduction in IBA1-positive macrophages in the outer retina compared to the WT mice and a decrease in the number of CD68-positive cells in the outer nuclear layer and the subretinal space. In addition, the engulfment of TUNEL-positive and -negative photoreceptors by macrophages was significantly lower in the C3 KO mice cohort following photooxidative damage compared to the WT cohort.
   Conclusions: The results show that the absence of C3 mitigates the phagocytosis of photoreceptors by macrophages in the outer retina, and the net impact of C3 depletion is neuroprotective in the context of photo-oxidative damage. These data improve our understanding of the impact of C3 inhibition in subretinal inflammation and inform the development of treatments for targeting complement activation in diseases such as AMD.
C1 [Jiao, Haihan] Univ Melbourne, Dept Optometry & Vis Sci, Melbourne, Vic, Australia.
   [Jiao, Haihan; Provis, Jan M.; Natoli, Riccardo] Australian Natl Univ, John Curtin Sch Med Res, Acton, Australia.
   [Provis, Jan M.; Natoli, Riccardo] Australian Natl Univ, Med Sch, Acton, Australia.
   [Rutar, Matt] Univ Melbourne, Dept Anat & Neurosci, Melbourne, Vic, Australia.
C3 University of Melbourne; Australian National University; John Curtin
   School of Medical Research; Australian National University; University
   of Melbourne
RP Jiao, HH (通讯作者)，Univ Melbourne, Parkville, Vic 3052, Australia.
EM helen.jiao@unimelb.edu.au
OI Natoli, Riccardo/0000-0002-9350-0439; Rutar,
   Matthew/0000-0002-8893-5120; Jiao, Haihan/0000-0002-5404-9307
FU National Health and Medical Research Council [APP1165599, APP1127705];
   Australian National University Translational Fellowship; Australian
   Government Research Training Program Scholarship
FX This study was supported by project grants from the National Health and
   Medical Research Council (APP1165599; APP1127705), Australian National
   University Translational Fellowship and Australian Government Research
   Training Program Scholarship.
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NR 41
TC 4
Z9 4
U1 1
U2 2
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD OCT 10
PY 2020
VL 26
BP 679
EP 690
PG 12
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA NZ5OB
UT WOS:000577152700001
PM 33088172
DA 2022-11-30
ER

PT J
AU Vila, N
   Siblini, A
   Esposito, E
   Bravo, V
   Zoroquiain, P
   Aldrees, S
   Logan, P
   Arias, L
   Burnier, MN
AF Vila, Natalia
   Siblini, Aya
   Esposito, Evangelina
   Bravo-Filho, Vasco
   Zoroquiain, Pablo
   Aldrees, Sultan
   Logan, Patrick
   Arias, Lluis
   Burnier, Miguel N.
TI Blue-light filtering alters angiogenic signaling in human retinal
   pigmented epithelial cells culture model
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Blue light filters; RPE cell line; Angiogenesis; Age-related macular
   degeneration
ID ENDOTHELIAL GROWTH-FACTOR; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; INTRAOCULAR-LENS; PROTECTIVE ROLE; LUTEIN; PATHOGENESIS;
   SECRETION; HYPOXIA; DAMAGE
AB Background: Light exposure and more specifically the spectrum of blue light contribute to the oxidative stress in Age-related macular degeneration (AMD). The purpose of the study was to establish whether blue light filtering could modify proangiogenic signaling produced by retinal pigmented epithelial (RPE) cells under different conditions simulating risk factors for AMD.
   Methods: Three experiments were carried out in order to expose ARPE-19 cells to white light for 48 h with and without blue light-blocking filters (BLF) in different conditions. In each experiment one group was exposed to light with no BLF protection, a second group was exposed to light with BLF protection, and a control group was not exposed to light. The ARPE-19 cells used in each experiment prior to light exposure were cultured for 24 h as follows: Experiment 1) Normoxia, Experiment 2) Hypoxia, and Experiment 3) Lutein supplemented media in normoxia. The media of all groups was harvested after light exposure for sandwich ELISA-based assays to quantify 10 pro-angiogenic cytokines.
   Results: A significant decrease in angiogenin secretion levels and a significant increase in bFGF were observed following light exposure, compared to dark conditions, in both normoxia and hypoxia conditions. With the addition of a blue light-blocking filter in normoxia, a significant increase in angiogenin levels was observed. Although statistical significance was not achieved, blue light filters reduce light-induced secretion of bFGF and VEGF to near normal levels. This trend is also observed when ARPE-19 cells are grown under hypoxic conditions and when pre-treated with lutein prior to exposure to experimental conditions.
   Conclusions: Following light exposure, there is a decrease in angiogenin secretion by ARPE-19 cells, which was abrogated with a blue light - blocking filter. Our findings support the position that blue light filtering affects the secretion of angiogenic factors by retinal pigmented epithelial cells under normoxic, hypoxic, and lutein-pretreated conditions in a similar manner.
C1 [Vila, Natalia; Siblini, Aya; Esposito, Evangelina; Bravo-Filho, Vasco; Zoroquiain, Pablo; Aldrees, Sultan; Logan, Patrick; Burnier, Miguel N.] McGill Univ, Pathol Dept, Henry C Witelson Ocular Pathol Lab, Montreal, PQ, Canada.
   [Vila, Natalia; Arias, Lluis] Barcelona Univ, Ophthalmol Dept, Hosp Univ Bellvitge, Barcelona, Spain.
C3 McGill University; Institut d'Investigacio Biomedica de Bellvitge
   (IDIBELL); Bellvitge University Hospital; University of Barcelona
RP Vila, N (通讯作者)，McGill Univ, Pathol Dept, Henry C Witelson Ocular Pathol Lab, Montreal, PQ, Canada.; Vila, N (通讯作者)，Barcelona Univ, Ophthalmol Dept, Hosp Univ Bellvitge, Barcelona, Spain.
EM natalia.vila@mail.mcgill.ca
RI Filho, Vasco/N-6993-2018
OI Filho, Vasco/0000-0003-4460-3236; Zoroquiain, Pablo/0000-0002-3164-1842
FU Fundacion Alfonso Martin Escudero (FAME)
FX Natalia Vila is supported by a research grant from Fundacion Alfonso
   Martin Escudero (FAME).
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NR 45
TC 7
Z9 7
U1 0
U2 6
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD NOV 2
PY 2017
VL 17
AR 198
DI 10.1186/s12886-017-0592-2
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FL8SL
UT WOS:000414520600002
PM 29096624
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Bharathidevi, SR
   Babu, KA
   Jain, N
   Muthukumaran, S
   Umashankar, V
   Biswas, J
   Angayarkanni, N
AF Bharathidevi, Subramaniam Rajesh
   Babu, Kannadasan Anand
   Jain, Nishit
   Muthukumaran, Sivashanmugam
   Umashankar, Vetrivel
   Biswas, J.
   Angayarkanni, Narayanasamy
TI Ocular distribution of antioxidant enzyme paraoxonase & its alteration
   in cataractous lens & diabetic retina
SO INDIAN JOURNAL OF MEDICAL RESEARCH
LA English
DT Article
DE Antioxidant; cataract; diabetic retinopathy; ocular tissue; paraoxonase;
   PON1
ID GLYCATION END-PRODUCTS; PON1 ARYLESTERASE ACTIVITY;
   LOW-DENSITY-LIPOPROTEIN; OXIDATIVE STRESS; PLASMA PARAOXONASE;
   BEHCETS-DISEASE; HOMOCYSTEINE; EXPRESSION; OCCLUSION; PROTEIN
AB Background & objectives: The enzyme paraoxonase (PON), an antioxidant enzyme that has both arylesterase and thiolactonase activity, is well studied in cardiovascular diseases. Although a few studies have shown altered PON activity in ocular diseases such as age-related macular degeneration and diabetic retinopathy, but the tissue-wise expression of PON in its three gene forms has not been studied. This study was conducted to see the ocular distribution of PON for any altered expression in ocular pathologies such as in cataract and diabetes mellitus.
   Methods: Immunohistochemistry (IHC) of the ocular tissues was done for localizing all three forms of the PON in the human donor eyeballs. The PON arylesterase (PON-AREase) and thiolactonase (PON-HCTLase) activities were determined by spectrophotometry in kinetic mode, and the mRNA expression of the PON genes (PON1-3) was determined by reverse transcription-polymerase chain reaction.
   Results: IHC showed the presence of both PON1 and 2 in all the ocular tissues and PON3 was seen only in retina. The mRNA expression analysis showed that PON2 and PON3 were present in all the tissues, whereas PON1 was seen only in ciliary and retina. Both the PON-AREase and PON-HCTLase activities were detected in all ocular tissues and was in the order of lens>retina>choroid>ciliary body>iris. The expression and activity were studied in cataractous lens and in diabetic retina of the donor eyes. A significant decrease in PON-AREase activity was seen in cataractous lens (P<0.05) but not in diabetic retina, and there was an increase in PON-HCTLase activity (P<0.05) only in diabetic retina. Bioinformatic studies and in vitro experiments indicated that advanced glycation end products (AGE) such as carboxymethyl -lysine might decrease the PON-AREase activity of the PON.
   Interpretation & conclusions: Distribution of PON enzyme and its activity in ocular tissues is reported here. The study revealed maximal PON activity in lens and retina, which are prone to higher oxidative stress. Differential activities of PON were observed in the lens and retinal tissues from cataractous and diabetic patients, respectively.
C1 [Bharathidevi, Subramaniam Rajesh; Babu, Kannadasan Anand; Angayarkanni, Narayanasamy] Vis Res Fdn, RS Mehta Jain Dept Biochem & Cell Biol, KBIRVO Block,41 Coll Rd, Chennai 600006, Tamil Nadu, India.
   [Muthukumaran, Sivashanmugam; Umashankar, Vetrivel] Vis Res Fdn, Ctr Bioinformat, KBIRVO Block, Chennai, Tamil Nadu, India.
   [Jain, Nishit] Birla Inst Technol & Sci, Dept Pharm, Pilani, Rajasthan, India.
   [Biswas, J.] Sankara Nethralaya, Uveitis Serv, Chennai, Tamil Nadu, India.
C3 Birla Institute of Technology & Science Pilani (BITS Pilani)
RP Angayarkanni, N (通讯作者)，Vis Res Fdn, RS Mehta Jain Dept Biochem & Cell Biol, KBIRVO Block,41 Coll Rd, Chennai 600006, Tamil Nadu, India.
EM drak@snmail.org
RI K, Anand Babu/AAN-8619-2020; Narayanasamy, Angayarkanni/ABD-8584-2020
OI K, Anand Babu/0000-0002-9910-2044; 
FU Indian Council of Medical Research (ICMR) [52/3/2008-BMS]; Department of
   Biotechnology (DBT), New Delhi, India [IR/SO/LU/03/2008/1]
FX Authors acknowledge financial support from Indian Council of Medical
   Research (ICMR) (No-52/3/2008-BMS) and Department of Biotechnology (DBT)
   (No-IR/SO/LU/03/2008/1), New Delhi, India.
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NR 31
TC 6
Z9 7
U1 0
U2 3
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
   INDIA
SN 0971-5916
J9 INDIAN J MED RES
JI Indian J. Med. Res.
PD APR
PY 2017
VL 145
BP 513
EP 520
DI 10.4103/ijmr.IJMR_1284_14
PG 8
WC Immunology; Medicine, General & Internal; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; General & Internal Medicine; Research & Experimental
   Medicine
GA FE9XD
UT WOS:000408555900014
PM 28862184
DA 2022-11-30
ER

PT J
AU Downes, SM
AF Downes, S. M.
TI Ultraviolet or blue-filtering intraocular lenses: what is the evidence?
SO EYE
LA English
DT Article
ID COLOR-VISION; GLARE DISABILITY; VISUAL FUNCTION; SCOTOPIC SENSITIVITY;
   CONTRAST SENSITIVITY; CATARACT-SURGERY; LIGHT; BLOCKING; PROTECTION;
   QUALITY
AB Cataract surgery was revolutionised by the introduction of modern intraocular lenses in the late 1940's. By the late 1960's to 1970's evidence had emerged that short-wavelength light caused phototoxicity at the retina and retinal pigment epithelium. By the early 1980's ultraviolet filters had been incorporated into intraocular lenses. This caused intense controversy, as there was concern that the UV-filtering chromophore might leach out into the eye causing toxicity. With the arrival of blue-filtering intraocular lenses (BFIOLs) in 1990's, a further debate was ignited as to their safety and potential disadvantages. Selecting the optimal performing intraocular lens to obtain the best visual performance with the fewest potential drawbacks has become complex and challenging for cataract surgeons and their patients with the wide choice of lenses available. Choosing a personalised lens to address astigmatism, presbyopia, spherical aberration, chromatic aberration, and potentially to shield the retina from short-wavelength light is now possible. The potential benefits and possible side effects of these different innovations emphasise the importance of assessing the evidence for their clinical utility, allowing the surgeon and the patient to weigh-up the risk benefit ratio and make an informed decision. The BFIOLs were developed to reduce cyanopsia, address chromatic aberration, and improve contrast sensitivity in different lighting conditions, as well as to prevent short-wavelength light reaching the retina thus potentially reducing the risk of developing age-related macular degeneration. Further design development of the BFIOLs was to mimic the natural crystalline lens absorption and transmittance properties in adulthood. Multiple publications have reported on the potential benefits and pitfalls of implanting a blue-filtering lens. The potential disadvantages raised in the literature over the last 25 years since their introduction, regarding compromise of visual function and disruption of the circadian system, have been largely dispelled. The clear benefits of protecting the retina from short-wavelength light make a BFIOLs a sensible choice. The purpose of this article presented at the Cambridge symposium 2015 is to review the literature on this subject.
C1 [Downes, S. M.] Oxford Univ Hosp Fdn Trust, Oxford Eye Hosp, Oxford, England.
   [Downes, S. M.] Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX3 9DU, England.
C3 Oxford University Hospitals NHS Foundation Trust; University of Oxford
RP Downes, SM (通讯作者)，Univ Oxford, Oxford Univ Hosp Fdn Trust, Oxford Eye Hosp, Ophthalmol,John Radcliffe, West Wing,Headley Way, Oxford OX3 9DU, England.
EM susan.downes@eye.ox.ac.uk
FU Wellcome Trust Grant [047473]; Oxford Biomedical Centre of Excellence
FX This work was part funded from a Wellcome Trust Grant (047473). The
   author is funded by the Oxford Biomedical Centre of Excellence.
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NR 69
TC 14
Z9 15
U1 1
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD FEB
PY 2016
VL 30
IS 2
BP 215
EP 221
DI 10.1038/eye.2015.267
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DE2HX
UT WOS:000370449500009
PM 26742866
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Land, ME
   Cooper, RF
   Young, J
   Berg, E
   Kitchner, T
   Xiang, Q
   Szabo, A
   Ivacic, LC
   Stepien, KE
   Page, CD
   Carroll, J
   Connor, T
   Brilliant, M
AF Land, Megan E.
   Cooper, Robert F.
   Young, Jonathon
   Berg, Elizabeth
   Kitchner, Terrie
   Xiang, Qun
   Szabo, Aniko
   Ivacic, Lynn C.
   Stepien, Kimberly E.
   Page, C. David
   Carroll, Joseph
   Connor, Thomas, Jr.
   Brilliant, Murray
TI Cone Structure in Subjects with Known Genetic Relative Risk for AMD
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE age-related macular degeneration; adaptive optics; photoreceptor
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; ADAPTIVE OPTICS;
   AGE; DRUSEN; DISEASE; OPHTHALMOSCOPE; DENSITY; EYES
AB Purpose. Utilize high-resolution imaging to examine retinal anatomy in patients with known genetic relative risk (RR) for developing age-related macular degeneration (AMD).
   Methods. Forty asymptomatic subjects were recruited (9 men, 31 women; age range, 51 to 69 years; mean age, 61.4 years). Comprehensive eye examination, fundus photography, and high-resolution retinal imaging using spectral domain optical coherence tomography and adaptive optics were performed on each patient. Genetic RR scores were developed using an age-independent algorithm. Adaptive optics scanning light ophthalmoscope images were acquired in the macula extending to 10 degrees temporal and superior from fixation and were used to calculate cone density in up to 35 locations for each subject.
   Results. Relative risk was not significantly predictive of fundus grade (p = 0.98). Only patients with a high RR displayed drusen on Cirrus or Bioptigen OCT. Compared to an eye with a grade of 0, an eye with a fundus grade equal to or greater than 1 had a 12% decrease in density (p < 0.0001) and a 5% increase in spacing (p = 0.0014). No association between genetic RR and either cone density (p = 0.435) or spacing (p = 0.538) was found. Three distinct adaptive optics scanning light ophthalmoscope phenotypical variations of photoreceptor appearance were noted in patients with grade 1 to 3 fundi. These included variable reflectivity of photoreceptors, decreased waveguiding, and altered photoreceptor mosaic overlying drusen.
   Conclusions. Our data demonstrate the potential of multimodal assessment in the understanding of early anatomical changes associated with AMD. Adaptive optics scanning light ophthalmoscope imaging reveals a decrease in photoreceptor density and increased spacing in patients with grade 1 to 3 fundi, as well as a spectrum of photoreceptor changes, ranging from variability in reflectivity to decreased density. Future longitudinal studies are needed in genetically characterized subjects to assess the significance of these findings with respect to the development and progression of AMD.
C1 [Land, Megan E.; Young, Jonathon; Stepien, Kimberly E.; Carroll, Joseph; Connor, Thomas, Jr.] Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA.
   [Xiang, Qun; Szabo, Aniko; Page, C. David] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA.
   [Cooper, Robert F.] Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53233 USA.
   [Berg, Elizabeth] Univ Wisconsin, Dept Comp Sci, Madison, WI 53706 USA.
   [Kitchner, Terrie; Brilliant, Murray] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA.
   [Ivacic, Lynn C.] Marshfield Clin Res Fdn, Core Lab, Marshfield, WI USA.
C3 Medical College of Wisconsin; Medical College of Wisconsin; Marquette
   University; University of Wisconsin System; University of Wisconsin
   Madison
RP Brilliant, M (通讯作者)，1000 N Oak Ave, Marshfield, WI 54449 USA.
EM brilliant.murray@mcrf.mfldclin.edu
FU Wisconsin Genome Initiative; Gene and Ruth Posner Foundation; RD & Linda
   Peters Foundation; National Institutes of Health (NIH) [U01HG006389,
   P30EY001931]; Research Facilities Improvement Program; National Center
   for Research Resources, NIH [C06RR016511]; National Center for Advancing
   Translational Sciences, NIH [UL1TR000055, UL1TR000427]; Research to
   Prevent Blindness; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
   [UL1TR000427, UL1TR000055] Funding Source: NIH RePORTER; NATIONAL CENTER
   FOR RESEARCH RESOURCES [C06RR016511] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R01EY017607, P30EY001931] Funding Source: NIH
   RePORTER; NATIONAL HUMAN GENOME RESEARCH INSTITUTE [U01HG006389] Funding
   Source: NIH RePORTER
FX This study was funded by grants from the Wisconsin Genome Initiative,
   Research to Prevent Blindness, the Gene and Ruth Posner Foundation, and
   the RD & Linda Peters Foundation. This study was partially supported by
   National Institutes of Health (NIH) grants U01HG006389 and P30EY001931.
   This investigation was conducted in part in a facility constructed with
   support from the Research Facilities Improvement Program and grant
   C06RR016511 from the National Center for Research Resources, NIH. This
   project was supported in part by the National Center for Advancing
   Translational Sciences, NIH, through grant numbers UL1TR000055 and
   UL1TR000427. Its contents are solely the responsibility of the authors
   and do not necessarily represent the official views of the NIH.
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NR 27
TC 13
Z9 13
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-5488
EI 1538-9235
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD AUG
PY 2014
VL 91
IS 8
BP 939
EP 949
DI 10.1097/OPX.0000000000000323
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AN4KL
UT WOS:000340556500018
PM 25014365
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Wittchen, ES
   Nishimura, E
   McCloskey, M
   Wang, H
   Quilliam, LA
   Chrzanowska-Wodnicka, M
   Hartnett, ME
AF Wittchen, Erika S.
   Nishimura, Eiichi
   McCloskey, Manabu
   Wang, Haibo
   Quilliam, Lawrence A.
   Chrzanowska-Wodnicka, Magdalena
   Hartnett, M. Elizabeth
TI Rap1 GTPase Activation and Barrier Enhancement in RPE Inhibits Choroidal
   Neovascularization In Vivo
SO PLOS ONE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL-CELL TRANSMIGRATION;
   GROWTH-FACTOR; MACULAR DEGENERATION; LIGHT-CHAIN; RHO-GTPASES;
   ANGIOGENESIS; JUNCTIONS; CONTACT; VEGF
AB Loss of barrier integrity precedes the development of pathologies such as metastasis, inflammatory disorders, and blood-retinal barrier breakdown present in neovascular age-related macular degeneration. Rap1 GTPase is involved in regulating both endothelial and epithelial cell junctions; the specific role of Rap1A vs. Rap1B isoforms is less clear. Compromise of retinal pigment epithelium barrier function is a contributing factor to the development of AMD. We utilized shRNA of Rap1 isoforms in cultured human retinal pigment epithelial cells, along with knockout mouse models to test the role of Rap1 on promoting RPE barrier properties, with emphasis on the dynamic junctional regulation that is triggered when the adhesion between cells is challenged. In vitro, Rap1A shRNA reduced steady-state barrier integrity, whereas Rap1B shRNA affected dynamic junctional responses. In a laser-induced choroidal neovascularization (CNV) model of macular degeneration, Rap1b(-/-) mice exhibited larger CNV volumes compared to wild-type or Rap1a(-/-). In vivo, intravitreal injection of a cAMP analog (8CPT-2'-O-Me-cAMP) that is a known Rap1 activator significantly reduced laser-induced CNV volume, which correlated with the inhibition of CEC transmigration across 8CPT-2'O-Me-cAMP-treated RPE monolayers in vitro. Rap1 activation by 8CPT-2'-O-Me-cAMP treatment increased recruitment of junctional proteins and F-actin to cell-cell contacts, increasing both the linearity of junctions in vitro and in cells surrounding laser-induced lesions in vivo. We conclude that in vitro, Rap1A may be important for steady state barrier integrity, while Rap1B is involved more in dynamic junctional responses such as resistance to junctional disassembly induced by EGTA and reassembly of cell junctions following disruption. Furthermore, activation of Rap1 in vivo inhibited development of choroidal neovascular lesions in a laser-injury model. Our data suggest that targeting Rap1 isoforms in vivo with 8CPT-2'-O-Me-cAMP may be a viable pharmacological means to strengthen the RPE barrier against the pathological choroidal endothelial cell invasion that occurs in macular degeneration.
C1 [Wittchen, Erika S.] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC USA.
   [Nishimura, Eiichi; McCloskey, Manabu; Wang, Haibo; Hartnett, M. Elizabeth] Univ Utah, Moran Eye Ctr, Salt Lake City, UT 84108 USA.
   [Quilliam, Lawrence A.] Indiana Univ, Dept Biochem & Mol Biol, Indianapolis, IN 46204 USA.
   [Chrzanowska-Wodnicka, Magdalena] Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI USA.
   [Nishimura, Eiichi] Showa Univ, Dept Ophthalmol, Tokyo, Japan.
C3 University of North Carolina; University of North Carolina Chapel Hill;
   Utah System of Higher Education; University of Utah; Indiana University
   System; Indiana University-Purdue University Indianapolis; Versiti Blood
   Center of Wisconsin; Showa University
RP Hartnett, ME (通讯作者)，Univ Utah, Moran Eye Ctr, Salt Lake City, UT 84108 USA.
EM ME.Hartnett@hsc.utah.edu
RI Quilliam, Lawrence/B-6447-2015; Quilliam, Lawrence/Q-4987-2019
OI Chrzanowska, Magdalena/0000-0003-4182-2126
FU National Institutes of Health (NIH) [R01 EY017011, R01 EY015130]; U.S.
   Department of Defense [W81XWH1110355]; NIH [R01 HL111582]; American
   Heart Association [10SDG3430042];  [R01-GM029860];  [P01 HL-080166];
   NATIONAL EYE INSTITUTE [P30EY014800, R01EY017011, R01EY015130] Funding
   Source: NIH RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
   [R01HL111582, P01HL080166] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM029860] Funding Source: NIH
   RePORTER
FX National Institutes of Health (NIH) R01 EY017011 and R01 EY015130 (to M.
   E. H.); U.S. Department of Defense award W81XWH1110355 (to L. A. Q.);
   NIH R01 HL111582 (to M.C.-W.); American Heart Association Scientist
   Development Grant 10SDG3430042 (to E. S. W.); R01-GM029860, and P01
   HL-080166. Department support from Research to Prevent Blindness
   (University of Utah). The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 74
TC 22
Z9 22
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 10
PY 2013
VL 8
IS 9
AR e73070
DI 10.1371/journal.pone.0073070
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 259PK
UT WOS:000327538600015
PM 24039860
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Evoy, KE
   Abel, SR
AF Evoy, Kirk E.
   Abel, Steven R.
TI Aflibercept: Newly Approved for the Treatment of Macular Edema Following
   Central Retinal Vein Occlusion
SO ANNALS OF PHARMACOTHERAPY
LA English
DT Article
ID FACTOR TRAP-EYE; INTRAVITREAL AFLIBERCEPT; TRIAL; DEGENERATION;
   SECONDARY; PHOTOCOAGULATION; RANIBIZUMAB
AB OBJECTIVE: To review the pharmacology, efficacy, and safety data available for aflibercept and compare the drug to other therapeutic options for treatment of macular edema following central retinal vein occlusion (CRVO) to determine its likely role in therapy.
   DATA SOURCES: A PubMed search using the terms aflibercept and VEGF trap-eye was conducted to identify initial literature sources. No timeframe was used for exclusion of older trials. All trials referenced were published between January 1995 and December 2012.
   STUDY SELECTION AND DATA EXTRACTION: Trials pertaining to oncologic use were excluded, as were studies conducted in animals and those written in a language other than English. Abstracts of the remaining trials were evaluated for determination of relevance to this review. Additional information sources were obtained via Internet and PubMed following a review of references.
   DATA SYNTHESIS: While previous Phase 1, 2, and 3 trials for other indications (age-related macular degeneration and diabetic macular edema) have shown intravitreal injections of aflibercept to be safe and well tolerated in many patients, preliminary results from the ongoing COPERNICUS and GALILEO trials proved the efficacy of this medication in treating macular edema secondary to CRVO. Of the combined 358 patients studied in COPERNICUS and GALILEO, 56% and 60%, respectively, of the patients receiving aflibercept 2 mg monthly achieved at least a 15-letter improvement in best-corrected visual acuity (BCVA) from baseline over 6 months compared with just 12% and 22% in the control group (p < 0.01 for both). Additionally, in COPERNICUS and GALILEO, patients achieved a 21.3- and 14.7-letter improvement, respectively, in BCVA compared with placebo (p < 0.01 for both).
   CONCLUSIONS: In September 2012, aflibercept became the second vascular endothelial growth factor (VEGF) inhibitor approved for treatment of macular edema secondary to CRVO. While efficacy and safety appear similar to other anti-VEGF treatments, the higher potency, binding affinity, and duration of action make aflibercept an appealing new option.
C1 [Evoy, Kirk E.] Purdue Univ, Coll Pharm, Lafayette, IN USA.
   [Abel, Steven R.] Purdue Univ, Coll Pharm, Clin Programs, Lafayette, IN 47907 USA.
C3 Purdue University System; Purdue University; Purdue University System;
   Purdue University
RP Abel, SR (通讯作者)，Purdue Univ, Coll Pharm, Clin Programs, Lafayette, IN 47907 USA.
EM abels@purdue.edu
CR [Anonymous], 2011, 2 YEAR RES PHAS 3 ST
   [Anonymous], 2012, PACK INS EYL AFL
   [Anonymous], 2011, REG BAYER REP POS RE
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   Regillo CD, 2008, AM J OPHTHALMOL, V145, P239, DOI 10.1016/j.ajo.2007.10.004
NR 27
TC 10
Z9 12
U1 0
U2 11
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1060-0280
EI 1542-6270
J9 ANN PHARMACOTHER
JI Ann. Pharmacother.
PD JUN
PY 2013
VL 47
IS 6
BP 819
EP 827
DI 10.1345/aph.1R705
PG 9
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 225UH
UT WOS:000324988200011
PM 23673531
DA 2022-11-30
ER

PT J
AU Michalewska, Z
   Michalewski, J
   Odrobina, D
   Nawrocki, J
AF Michalewska, Zofia
   Michalewski, Janusz
   Odrobina, Dominik
   Nawrocki, Jerzy
TI NON-FULL-THICKNESS MACULAR HOLES REASSESSED WITH SPECTRAL DOMAIN OPTICAL
   COHERENCE TOMOGRAPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE lamellar macular hole; macular hole; non-full-thickness macular hole;
   partial thickness macular hole; pseudohole; spectral domain OCT; SOCT
   SD-OCT
ID PSEUDOHOLES; VITRECTOMY; DIAGNOSIS
AB Purpose: The aim of this study was to describe spectral domain optical coherence tomography characteristics and evolution of non-full-thickness macular holes, with a bed of retinal tissue present in the outer retinal layers, which the author will henceforth refer to as non-full-thickness macular holes (NFMHs).
   Methods: Retrospective observational study of 10,239 consecutive spectral domain optical coherence tomographic examinations was conducted, to select patients with idiopathic NFMH. We measured the following parameters: visual acuity, type of NFMH, coexistence of epiretinal membranes, photoreceptor layer defects, central and maximum retinal thickness, and diameters of the fovea defect. Patients with a history of diabetes; previous vein occlusions, with age-related macular degeneration; high and medium myopia; a previous history of retinal detachment; or macular edema were excluded.
   Results: Four subtypes of NFMH were distinguished among 125 eyes (116 patients): macular pseudohole (21 eyes), paralamellar macular holes (34 eyes), pseudoholes with lamellar defects (25 eyes), and lamellar macular holes (45 eyes). We observed different fovea appearances on consecutive B-scans in 54% of eyes. Epiretinal membranes coexisted in 100% of cases. Photoreceptor layer defects, seen in 29% of cases, were the most important factor correlating with visual acuity. Other factors correlating with visual acuity were maximum retinal thickness and outer diameter of the fovea defect. We noted epiretinal membranes in the second eye in 32 cases. Sixty-six patients were followed up for a mean time of 14 months. Non-full-thickness macular hole formation was documented in five cases.
   Conclusion: Spectral domain optical coherence tomography images presented of four different morphologic types NFMH, which may change during the natural course of the disease. High resolution of spectral domain optical coherence tomography enabled the visualization of photoreceptor defects, a feature not previously described. Moreover, epiretinal membranes and fovea contour localized beneath the outer plexiform layer were noted in all cases. RETINA 32:922-929, 2012
C1 [Michalewska, Zofia; Michalewski, Janusz; Odrobina, Dominik; Nawrocki, Jerzy] Ophthalm Clin, Lodz, Poland.
RP Michalewska, Z (通讯作者)，Klin Okulistyczna Jasne Blonia, Ul Rojna 90, PL-91162 Lodz, Poland.
EM zosia_n@yahoo.com
OI Michalewski, Janusz/0000-0002-1516-6703; Nawrocka, Zofia
   Anna/0000-0001-8376-9218
CR ALLEN AW, 1976, AM J OPHTHALMOL, V82, P684, DOI 10.1016/0002-9394(76)90002-7
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NR 16
TC 31
Z9 34
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAY
PY 2012
VL 32
IS 5
BP 922
EP 929
DI 10.1097/IAE.0b013e318227a9ef
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 935EQ
UT WOS:000303502200007
PM 21909051
DA 2022-11-30
ER

PT J
AU Luhmann, UFO
   Lange, CA
   Robbie, S
   Munro, PMG
   Cowing, JA
   Armer, HEJ
   Luong, V
   Carvalho, LS
   MacLaren, RE
   Fitzke, FW
   Bainbridge, JWB
   Ali, RR
AF Luhmann, Ulrich F. O.
   Lange, Clemens A.
   Robbie, Scott
   Munro, Peter M. G.
   Cowing, Jill A.
   Armer, Hannah E. J.
   Vy Luong
   Carvalho, Livia S.
   MacLaren, Robert E.
   Fitzke, Frederick W.
   Bainbridge, James W. B.
   Ali, Robin R.
TI Differential Modulation of Retinal Degeneration by Ccl2 and Cx3cr1
   Chemokine Signalling
SO PLOS ONE
LA English
DT Article
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; MACULAR DEGENERATION; MICROGLIAL
   CELLS; TRANSENDOTHELIAL MIGRATION; LESION FORMATION; DENDRITIC CELLS;
   ANIMAL-MODEL; MICE; MACROPHAGES; BLOOD
AB Microglia and macrophages are recruited to sites of retinal degeneration where local cytokines and chemokines determine protective or neurotoxic microglia responses. Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2(-/-)/Crb1(Rd8/RD8), Cx3cr1(-/-)/Crb1(Rd8/RD8) and CCl2(-/-)/Cx3cr1(-/-)/Crb1(Rd8/RD8) mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings indicate that CCDKO mice are not a model of AMD, but a model for an inherited retinal degeneration that is differentially modulated by Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling.
C1 [Luhmann, Ulrich F. O.; Lange, Clemens A.; Robbie, Scott; Cowing, Jill A.; Carvalho, Livia S.; MacLaren, Robert E.; Bainbridge, James W. B.; Ali, Robin R.] UCL Inst Ophthalmol, Dept Genet, London, England.
   [Munro, Peter M. G.; Armer, Hannah E. J.] UCL Inst Ophthalmol, Imaging Unit, London, England.
   [Vy Luong; Fitzke, Frederick W.] UCL Inst Ophthalmol, Dept Visual Sci, London, England.
   [Robbie, Scott; MacLaren, Robert E.; Bainbridge, James W. B.; Ali, Robin R.] UCL Inst Ophthalmol, Moorfields Eye Hosp, Natl Hlth Sci Fdn Trust, Natl Inst Hlth & Res Biomed Res,Ctr Ophthalmol, London, England.
C3 University of London; University College London; University of London;
   University College London; University of London; University College
   London; University of London; University College London; Moorfields Eye
   Hospital NHS Foundation Trust
RP Luhmann, UFO (通讯作者)，UCL Inst Ophthalmol, Dept Genet, London, England.
EM u.luhmann@ucl.ac.uk
RI Luhmann, Ulrich/D-8905-2012; Carvalho, Livia/B-4984-2013
OI Ali, Robin/0000-0003-3126-6517; Carvalho, Livia/0000-0002-3909-5778;
   Bainbridge, James/0000-0003-1318-8201; MacLaren,
   Robert/0000-0002-3096-4682
FU Wellcome Trust [074617/Z/04/Z]; National Institute for Health Research
   [NF-SI-0508-10130, NIHR-RP-011-003] Funding Source: researchfish
FX This work was funded by the Wellcome Trust fellowship 074617/Z/04/Z
   (http://www.wellcome.ac.uk/). The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 63
TC 53
Z9 53
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 24
PY 2012
VL 7
IS 4
AR e35551
DI 10.1371/journal.pone.0035551
PG 17
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 959VE
UT WOS:000305343200036
PM 22545116
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Luke, M
   Januschowski, K
   Warga, M
   Beutel, J
   Leitritz, M
   Gelisken, F
   Grisanti, S
   Schneider, T
   Luke, C
   Bartz-Schmidt, KU
   Szurman, P
AF Lueke, Matthias
   Januschowski, Kai
   Warga, Max
   Beutel, Julia
   Leitritz, Martin
   Gelisken, Faik
   Grisanti, Salvatore
   Schneider, Toni
   Lueke, Christoph
   Bartz-Schmidt, Karl Ulrich
   Szurman, Peter
CA Tuebingen Bevacizumab Study Grp
TI The retinal tolerance to bevacizumab in co-application with a
   recombinant tissue plasminogen activator
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; SUBMACULAR HEMORRHAGE;
   SUBRETINAL HEMORRHAGE; INTRAVITREAL BEVACIZUMAB; VERTEBRATE RETINA;
   NATURAL-HISTORY; BOVINE RETINA; TOXICITY; INJECTION
AB Aim: To investigate the retinal toxicity of bevacizumab in co-application with a commercially available recombinant tissue plasminogen activator (rt-PA), and to facilitate a new therapeutic concept in the treatment of massive subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD).
   Methods: Isolated bovine retinas were perfused with an oxygen-preincubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl electrodes. Bevacizumab (0.25 mg/ml) and rt-PA (20 mg/ml) were added to the nutrient solution for 45 min. Thereafter, the retina was reperfused for 60 min with normal nutrient solution. Similarly, the effects of rt-PA (20 mg/ml, 60 mg/ml and 200 mg/ml) on the a-and b-wave amplitudes were investigated. The percentages of a-and b-wave reduction during application and at washout were calculated.
   Results: During application of bevacizumab (0.25 mg/ml) in co-application with 20 mg/ml (rt-PA), the ERG amplitudes remained stable. The concentrations of rt-PA alone (20 mg/ml and 60 mg/ml) did not induce significant reduction of the b-wave amplitude. In addition, 20 mg/ml rt-PA did not alter the a-wave amplitude. However, 60 mg/ml rt-PA caused a slight but significant reduction of the a-wave amplitude. A full recovery was detected for both concentrations during the washout. At the highest tested concentration of 200 mg/ml rt-PA, a significant reduction of the a-and b-wave amplitudes was provoked during the exposure. The reduction of ERG amplitudes remained irreversible during the washout.
   Conclusion: The present study suggests that a subretinal injection of 20 mg/ml rt-PA in co-application with bevacizumab (0.25 mg/ml) for the treatment of massive subretinal haemorrhage seems possible. This is a safety study. Therefore, we did not test the clinical effectiveness of this combined treatment.
C1 Univ Tubingen, Univ Eye Hosp, Ctr Ophthalmol, D-72076 Tubingen, Germany.
   Univ Cologne, Inst Neurophysiol, D-5000 Cologne 41, Germany.
   Univ Cologne, Ctr Ophthalmol, D-5000 Cologne 41, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; University of Cologne; University of Cologne
RP Luke, M (通讯作者)，Univ Tubingen, Dept Ophthalmol, Schleich Str 12-16, D-72076 Tubingen, Germany.
EM matthias.lueke@med.uni-tuebingen.de
OI Leitritz, Martin/0000-0001-5179-2536
CR Avery RL, 1996, RETINA-J RET VIT DIS, V16, P183, DOI 10.1097/00006982-199616030-00001
   Bakri SJ, 2006, AM J OPHTHALMOL, V142, P162, DOI 10.1016/j.ajo.2006.03.058
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NR 33
TC 34
Z9 35
U1 0
U2 3
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD AUG
PY 2007
VL 91
IS 8
BP 1077
EP 1082
DI 10.1136/bjo.2006.111260
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 190WD
UT WOS:000248090400023
PM 17383998
OA Green Published
DA 2022-11-30
ER

PT J
AU Elliot, S
   Catanuto, P
   Stetler-Stevenson, W
   Cousins, SW
AF Elliot, S
   Catanuto, P
   Stetler-Stevenson, W
   Cousins, SW
TI Retinal pigment epithelium protection from oxidant-mediated loss of
   MMP-2 activation requires both MMP-14 and TIMP-2
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID TYPE-1 MATRIX-METALLOPROTEINASE; TISSUE INHIBITOR; CELL-SURFACE; MACULAR
   DEGENERATION; ESTROGEN-RECEPTORS; FUNDUS DYSTROPHY; BRUCHS MEMBRANE;
   MESANGIAL CELLS; EXPRESSION; PROGELATINASE
AB PURPOSE. Eyes with age-related macular degeneration (AMD) demonstrate accumulation of specific deposits and extracellular matrix (ECM) molecules under the retinal pigment epithelium (RPE). Metalloproteinases (MMP) are crucial regulators of basement membrane and ECM turnover. Accordingly, loss of RPE MMP activity most likely leads to excessive accumulation of Collagen and other ECM, a potential mechanism for formation of deposits. A prior Study showed that MMP-2 activity, but not pro-MMP-2 protein, decreases after RPE oxidative injury, indicating that oxidant injure, disrupts the enzymatic cleavage of pro-MMP-2. Activation of MMP-2 requires the formation of a tri-molecular complex of pro-MMP-2, MMP-14, and tissue inhibitor of metalloproteinases (TIMP)-2. Therefore, a study was conducted to investigate the impact of oxidant injury on the interaction between these three molecules.
   METHODS. Human GFP-RPE cells were oxidant injured by transient exposure to H,02 and myeloperoxidase, and the time course of recovery determined. Supernatants and cell lysates were collected for analysis of MMP-2, MMP-14, and TIMP-2 activity, mRNA and protein expression. In some studies, overexpression with either MMP-14 or TIMP-2 was performed to revert the cells to a preinjury phenotype.
   RESULTS. Transient injury resulted in a decrease of both MMP-14 and TIMP-2 activity and protein. Overexpression of each single molecule failed to prevent the injury-induced decrease of MMP-2 activity. In contrast, overexpression of MMP-14 together with the addition of exogenous TIMP-2 prevented the reduction of MMP-2 activation.
   CONCLUSIONS. Loss of MMP-2 activity after oxidant injury is caused by the downregulation of MMP-14 and TIMP-2. Overexpression of either MMP-14 or TIMP-2 alone before oxidant injury is not enough to prevent loss of MMP-2 activity. All three components of the tri-molecular complex must be present to preserve normal MMP-2 activity after oxidant injury.
C1 Univ Miami, Miller Sch Med, Dept Med, Vasc Biol Inst, Miami, FL 33136 USA.
   NCI, Lab Cell & Canc Biol, NIH, Bethesda, MD 20892 USA.
   Duke Univ, Ctr Eye, Duke Ctr Macular Degenerat, Durham, NC USA.
C3 University of Miami; National Institutes of Health (NIH) - USA; NIH
   National Cancer Institute (NCI); Duke University
RP Elliot, S (通讯作者)，Univ Miami, Miller Sch Med, Dept Med, Vasc Biol Inst, 1600 NW 10th Ave,RSMB 1043,R104, Miami, FL 33136 USA.
EM selliot@med.miami.edu
RI Stetler-Stevenson, William G/H-6956-2012; Stetler-Stevenson,
   William/AAE-3501-2020
OI Stetler-Stevenson, William G/0000-0002-5500-5808; Stetler-Stevenson,
   William/0000-0002-5500-5808
FU NATIONAL EYE INSTITUTE [R01EY014477] Funding Source: NIH RePORTER; NEI
   NIH HHS [R01 EY014477, R01 EY14477-02] Funding Source: Medline
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NR 39
TC 19
Z9 20
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2006
VL 47
IS 4
BP 1696
EP 1702
DI 10.1167/iovs.05-1258
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 029KI
UT WOS:000236560800058
PM 16565411
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Jonas, JB
   Kreissig, I
   Degenring, R
AF Jonas, JB
   Kreissig, I
   Degenring, R
TI Intravitreal triamcinolone acetonide for treatment of intraocular
   proliferative, exudative, and neovascular diseases
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
ID CYSTOID MACULAR EDEMA; PARS-PLANA VITRECTOMY; CENTRAL SEROUS
   CHORIORETINOPATHY; GRID LASER PHOTOCOAGULATION; AGE-RELATED MACULOPATHY;
   RETINAL VEIN OCCLUSION; CHOROIDAL NEOVASCULARIZATION; CRYSTALLINE
   CORTISONE; PHOTODYNAMIC THERAPY; ADJUNCTIVE TREATMENT
AB Within the last three years, triamcinolone acetonide has increasingly been applied intravitreally as treatment option for various intraocular neovascular edematous and proliferative disorders. The best response in terms of gain in visual acuity after the intravitreal injection of triamcinolone acetonide was found in eyes with intraretinal edematous diseases such as diffuse diabetic macular edema, branch retinal vein occlusion, central retinal vein occlusion, and pseudophakic cystoid macular edema. Visual acuity increased and degree of intraocular inflammation decreased in eyes with various types of non-infectious uveitis including acute or chronic sympathetic ophthalmia and Adamantiadis-Behcet's disease. Intravitreal triamcinolone may be useful as angiostatic therapy in eyes with iris neovascularization and proliferative ischemic retinopathies. Possibly, intravitreal triamcinolone may be helpful as adjunct therapy for exudative age-related macular degeneration, possibly in combination with photodynamic therapy. In eyes with chronic, therapy resistant, ocular hypotony, intravitreal triamcinolone can induce an increase in intraocular pressure and may stabilize the eye. The complications of intravitreal triamcinolone therapy include secondary ocular hypertension in about 40% of the eyes injected, cataractogenesis, postoperative infectious and non-infectious endophthalmitis, and pseudo-endophthalmitis. Intravitreal triamcinolone injection can be combined with other intraocular surgeries including cataract surgery. Cataract surgery performed some months after the injection does not show a markedly elevated rate of complications. If vision increases and eventually decreases again after an intravitreal triamcinolone acetonide injection, the injection can be repeated. The duration of the effect of a single intravitreal injection of triamcinolone depended on the dosage given. Given in a dosage of about 20 mg to non-vitrectornized eyes, the duration of the effect and of the side-effects was 6-9 months.
   Intravitreal triamcinolone acetonide may offer a possibility for adjunctive treatment of intraocular edematous and neovascular disorders. One has to take into account the side-effects and the lack of long-term follow-up observations. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Heidelberg Univ, Fac Clin Med Mannheim, Dept Ophthalmol, Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg
RP Jonas, JB (通讯作者)，Univ Augenklin, Theodor Kutzer Ufer 1-3, D-68467 Mannheim, Germany.
EM jost.jonas@augen.ma.uni-heidelberg.de
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NR 201
TC 121
Z9 129
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD SEP
PY 2005
VL 24
IS 5
BP 587
EP 611
DI 10.1016/j.preteyeres.2005.01.004
PG 25
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 952LQ
UT WOS:000231005400003
PM 16005407
DA 2022-11-30
ER

PT J
AU Hayreh, SS
   Jonas, JB
AF Hayreh, SS
   Jonas, JB
TI Posterior vitreous detachment: Clinical correlations
SO OPHTHALMOLOGICA
LA English
DT Article
DE posterior vitreous detachment; nonarteritic anterior ischemic optic
   neuropathy
ID RETINAL VEIN OCCLUSION; ISCHEMIC OPTIC NEUROPATHY; MACULAR EDEMA;
   DIABETIC-RETINOPATHY; PERIPHERAL RETINA; NATURAL-HISTORY; HOLE;
   PATHOGENESIS; EYES; NEOVASCULARIZATION
AB Background: To evaluate the frequency of, and the factors which are primarily and secondarily associated with, posterior vitreous detachment ( PVD), and to correlate the presence of PVD with various demographic and ophthalmic entities. Methods: The clinical prospective observational cohort study included 1,481 subjects (740 women, 741 men) with a mean age of 63.45+/-14.97 years (mean+/-SD; range, 10.3-94.9 years) and a mean spherical equivalent refractive error of +0.68+/-2.13 dpt (range, -14.25 to +13.50 dpt). The presence of PVD was assessed by indirect and direct ophthalmoscopy, fundus biomicroscopy and by using a Hruby lens upon pharmacologically dilated pupil. Main outcome measures were frequency of PVD, association with age, refractive error, cataract surgery, diabetes mellitus, arterial hypertension, history of ocular trauma, vitreous hemorrhage, various retinal disorders, nonarteritic anterior ischemic optic neuropathy (AION) and open-angle glaucoma. Results: The occurrence of PVD was significantly correlated with increasing age (p<0.001), myopic refractive error (p<0.001), female gender (p<0.001), and surgical aphakia (p<0.001). PVD occurred significantly more often bilaterally than unilaterally (p<0.001). Patients with unilateral PVD were significantly (p<0.001) younger than the patients with bilateral PVD. PVD was seen significantly (p=0.038) less frequently in AION than in the remaining study population. The frequency of PVD was lower in eyes with than without diabetic retinopathy (p=0.095), optic disc neovascularization (p=0.07) and retinal neovascularization (p=0.09). There was no significant association between the presence of PVD and macular hole, macular edema, retinal vascular occlusive disorders, age-related macular degeneration and open-angle glaucoma. Conclusions: These data of a large prospective study of PVD confirm some of the findings of previous smaller and retrospective studies. They also provide new information which may be helpful for the understanding of the pathophysiology of PVD and the role of PVD in the pathogenesis of various retinal and optic disc lesions. Copyright (C) 2004 S. Karger AG, Basel.
C1 Univ Iowa, Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
   Univ Heidelberg, Dept Ophthalmol, D-6800 Mannheim, Germany.
   Univ Heidelberg, Hosp Eye, Fac Clin Med Mannheim, D-6800 Mannheim, Germany.
C3 University of Iowa; Ruprecht Karls University Heidelberg; Ruprecht Karls
   University Heidelberg
RP Hayreh, SS (通讯作者)，Univ Hosp & Clin, Dept Ophthalmol & Visual Sci, 200 Hawkins Dr, Iowa City, IA 52242 USA.
EM sohan-hayreh@uiowa.edu
RI Hayreh, Sohan Singh/AFU-1623-2022
OI Hayreh, Sohan/0000-0002-0709-886X
FU NEI NIH HHS [EY-1576] Funding Source: Medline; NATIONAL EYE INSTITUTE
   [R01EY001576] Funding Source: NIH RePORTER
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NR 56
TC 55
Z9 59
U1 0
U2 6
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2004
VL 218
IS 5
BP 333
EP 343
DI 10.1159/000079476
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 855NO
UT WOS:000223980700008
PM 15334015
DA 2022-11-30
ER

PT J
AU Shukal, D
   Bhadresha, K
   Shastri, B
   Mehta, D
   Vasavada, A
   Johar, SRK
AF Shukal, Dhaval
   Bhadresha, Kinjal
   Shastri, Bhoomi
   Mehta, Deval
   Vasavada, Abhay
   Johar, Kaid S. R.
TI Dichloroacetate prevents TGF beta-induced epithelial-mesenchymal
   transition of retinal pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retinal pigment epithelium; ARPE-19; Epithelial-mesenchymal transition;
   Dichloroacetate; TGF beta; Proliferative retinopathies; MAPK/Erk
   pathway; PI3K/Akt pathway
ID GROWTH-FACTOR-BETA; SIGNALING PATHWAY; MOLECULAR-MECHANISMS; N-CADHERIN;
   CANCER; DCA; METABOLISM; SURVIVAL; EMT; TRANSDIFFERENTIATION
AB Proliferative retinopathies are associated with formation of fibrous epiretinal membranes. At present, there is no pharmacological intervention for the treatment of retinopathies. Cytokines such as TGF beta are elevated in the vitreous humor of the patients with proliferative vitro-retinopathy, diabetic retinopathy and age-related macular degeneration. TGF beta isoforms lead to epithelial-mesenchymal transition (EMT) or trans-differentiation of the retinal pigment epithelial (RPE) cells. PI3K/Akt and MAPK/Erk pathways play important roles in the EMT of RPE cells. Therefore, inhibition of EMT by pharmacological agents is an important therapeutic strategy in retinopathy. Dichloroacetate (DCA) is shown to prevent proliferation and EMT of cancer cell lines but its effects are not explored on the prevention of EMT of RPE cells. In the present study, we have investigated the role of DCA in preventing TGF beta 2 induced EMT of RPE cell line, ARPE-19. A wound-healing assay was utilized to detect the anti EMT effect of DCA. The expressions of EMT and cell adhesion markers were carried out by immunofluorescence, western blotting, and quantitative real-time PCR. The expression of MAPK/Erk and PI3K/Akt pathway members was carried out using western blotting. We found that TGF beta 2 exposure leads to an increase in the wound healing response, expression of EMT markers (Fibronectin, Collagen I, N-cadherin, MMP9, S100A4, alpha-SMA, Snai1, Slug) and a decrease in the expression of cell adhesion/epithelial markers (ZO-1, Connexin 43, E-cadherin). These changes were accompanied by the activation of PI3K/Akt and MAPK/Erk pathways. Simultaneous exposure of DCA along with TGF beta 2 significantly inhibited wound healing response, expression of EMT markers and cell adhesion/epithelial markers. Furthermore, DCA and TGFj32 effectively attenuated the activation of MAPK/Erk/ JNK and PI3K/Akt/GSK3 beta pathways. Our results demonstrate that DCA has a strong anti-EMT effect on the ARPE-19 cells and hence can be utilized as a therapeutic agent in the prevention of proliferative retinopathies.
C1 [Shukal, Dhaval; Bhadresha, Kinjal; Shastri, Bhoomi; Mehta, Deval; Vasavada, Abhay] Iladevi Cataract & IOL Res Ctr, Dept Cell & Mol Biol, Ahmadabad, Gujarat, India.
   [Shukal, Dhaval] Manipal Acad Higher Educ, Manipal, Karnataka, India.
   [Johar, Kaid S. R.] Gujarat Univ, Dept Zool, USSC, BMTC,Human Genet, Ahmadabad 380009, Gujarat, India.
C3 Manipal Academy of Higher Education (MAHE); Gujarat University
RP Johar, SRK (通讯作者)，Gujarat Univ, Dept Zool, USSC, BMTC,Human Genet, Ahmadabad 380009, Gujarat, India.
EM dhavalshukal@outlook.com; kinjalbhadresha@outlook.com;
   bhoomiishastri@gmail.com; devalmehta007@yahoo.com;
   icirc@abhayvasavada.com; kaidjohar@gujaratuniversity.ac.in
RI Johar, Kaid/AAC-9182-2021
FU Gujarat State Biotechnological Mission (GSBTM), Gandhinagar
   [GSBTM/MD/PROJECTS/SSA/1411/2014-15]; Council of Scientific and
   Industrial Research (CSIR), New Delhi [27(0299)/14/EMR-II]
FX Funding was obtained from Gujarat State Biotechnological Mission
   (GSBTM), Gandhinagar grant no GSBTM/MD/PROJECTS/SSA/1411/2014-15 and
   Council of Scientific and Industrial Research (CSIR), New Delhi grant
   27(0299)/14/EMR-II.
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NR 79
TC 16
Z9 17
U1 4
U2 14
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD AUG
PY 2020
VL 197
AR 108072
DI 10.1016/j.exer.2020.108072
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA NI9QA
UT WOS:000565679200006
PM 32473169
DA 2022-11-30
ER

PT J
AU Bilgic, A
   Kodjikian, L
   Chhablani, J
   Sudhalkar, A
   Trivedi, M
   Vasavada, V
   Vasavada, V
   Vasavada, S
   Srivastava, S
   Bhojwani, D
   Sudhalkar, A
AF Bilgic, Alper
   Kodjikian, Laurent
   Chhablani, Jay
   Sudhalkar, Anand
   Trivedi, Megha
   Vasavada, Viraj
   Vasavada, Vaishali
   Vasavada, Shail
   Srivastava, Samaresh
   Bhojwani, Deepak
   Sudhalkar, Aditya
TI Sustained Intraocular Pressure Rise after the Treat and Extend Regimen
   at 3 Years: Aflibercept versus Ranibizumab
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID INTRAVITREAL INJECTION; OCULAR HYPERTENSION; BEVACIZUMAB; ELEVATION;
   GLAUCOMA; INDIA
AB Purpose. To determine the risk factors associated with sustained intraocular pressure (IOP) rise in patients enrolled in the treat and extend (T&E) protocol receiving aflibercept/ranibizumab therapy for 3 years. Design. Retrospective, observational chart review. Setting. Multicentric. Patients. 789 patients (1021 eyes; 602 males) enrolled in T&E using aflibercept/ranibizumab for diabetic macular edema (DME), wet age-related macular degeneration (AMD), or macular edema in retinal vein occlusion (RVO). Intervention. The history, examination (clinical and special investigations), and treatment records were thoroughly scrutinized. Sustained IOP rise was defined as a rise in IOP above baseline by >= 6 mmHg and/or >24 mmHg on 2 or more consecutive visits. The Wilk-Shapiro test was used for confirming normality of data. The Mantel-Haenszel test and generalized estimating equations were used to analyse multicentric data as well as to analyse data from both eyes of the same patients in the event that both eyes were under therapy. The relative risk, chi-square test (with and without Yates' correction), and univariate and multivariate analysis were used wherever appropriate. Statistical significance was set at P<0.05. The primary outcome measure was the determination of risk factors for sustained IOP rise with ranibizumab/aflibercept therapy. Secondary outcome measures included determining the incidence of IOP rise (short term and sustained), visual field, and retinal nerve fibre layer (RNFL) changes. Results. The mean follow-up was 42.4 months. Male gender, South Asian ethnicity, older age, presence of AMD and vein occlusion, use of ranibizumab, higher number of injections, narrow angles, switch to bevacizumab/ranibizumab, and preexisting glaucoma were associated with sustained IOP rise. No significant visual field and RNFL changes were seen. The overall incidence was 8.91%. No patient required filtering surgery. No patient with IOP rise returned to baseline. Conclusion. IOP rise is an important consideration as the chronicity of the condition can eventually lead to glaucomatous changes in eyes with already compromised vision. Follow-ups and use of appropriate therapy can be determined correspondingly.
C1 [Bilgic, Alper; Sudhalkar, Aditya] Alpha Vis Augenzentrum, Bremerhaven, Germany.
   [Kodjikian, Laurent] Hosp Civil Croix Rousse, Lyon, France.
   [Chhablani, Jay] Pittsburgh Med Ctr, Pittsburgh, PA USA.
   [Sudhalkar, Anand; Trivedi, Megha; Sudhalkar, Aditya] MS Sudhalkar Med Res Fdn, Baroda, Gujarat, India.
   [Vasavada, Viraj; Vasavada, Vaishali; Vasavada, Shail; Srivastava, Samaresh; Bhojwani, Deepak; Sudhalkar, Aditya] Raghudeep Eye Hosp, Ahmadabad, Gujarat, India.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh
RP Sudhalkar, A (通讯作者)，Alpha Vis Augenzentrum, Bremerhaven, Germany.; Sudhalkar, A (通讯作者)，MS Sudhalkar Med Res Fdn, Baroda, Gujarat, India.; Sudhalkar, A (通讯作者)，Raghudeep Eye Hosp, Ahmadabad, Gujarat, India.
EM drbilgicalper@yahoo.com; kodjikian@gmail.com; jay.chhablani@gmail.com;
   sudhalkar@hotmail.com; megha_boptom21@yahoo.com;
   viraj@raghudeepeyeclinic.com; vaishali@raghudeepeyeclinic.com;
   shail@raghudeepeyeclinic.com; samaresh@raghudeepeyeclinic.com;
   deepak@raghudeepeyeclinic.com; adityasudhalkar@yahoo.com
RI Bilgic, Alper/AAQ-4072-2020
OI Chhablani, Jay/0000-0003-1772-3558
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NR 29
TC 9
Z9 9
U1 0
U2 1
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PD JAN 21
PY 2020
VL 2020
AR 7462098
DI 10.1155/2020/7462098
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KH8KS
UT WOS:000510900000004
PM 32051764
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Eamegdool, SS
   Sitiwin, EI
   Cioanca, AV
   Madigan, MC
AF Eamegdool, Steven S.
   Sitiwin, Ephrem I.
   Cioanca, Adrian V.
   Madigan, Michele C.
TI Extracellular matrix and oxidative stress regulate human retinal pigment
   epithelium growth
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Extracellular matrix; Retinal degeneration; Oxidative stress;
   Inflammation; Cell biology; Pro-inflammatory cytokines; Retinal pigment
   epithelium
ID MACULAR DEGENERATION; BRUCHS MEMBRANE; RPE CELLS; IN-VITRO; EXPRESSION;
   MIGRATION; COLLAGEN; PROLIFERATION; MACROPHAGES; COMPLEMENT
AB Age-related macular degeneration (AMD), the most common cause of vision loss with ageing, is characterised by degeneration of the photoreceptors and retinal pigment epithelium (RPE) and changes in the extracellular matrix (ECM) underlying the RPE. The pathogenesis of AMD is still not fully understood. In this study we investigated the in vitro growth and function of primary human RPE cells in response to different ECM substrates, including nitrite-modified ECM. We initially confirmed the presence of disorganised retinal glial and photoreceptor cells, marked retinal cytoplasmic and Bruch's membrane expression of nitro-tyrosine (an oxidative stress marker) and increased numbers of Iba1(+) macrophages/microglia in human donor eye sections (aged and AMD) using multi-marker immunohistochemistry (n = 3). Concurrently, we utilised two-photon microscopy to reveal topographical changes in flatmounts of RPE-associated ECM and in the underlying choroid of aged and AMD donor eyes (n = 3). To recapitulate these observations in vitro, we then used primary human RPE cells to investigate how different ECM proteins, including nitrite cross-linked RPE-secreted ECM, modified RPE cell growth and function. Collagen I or IV increased RPE attachment and spreading two-to three-fold, associated with significantly increased cell migration and proliferation, consistent with a preferential interaction with these matrix substrates. Primary human RPE cells grown on collagen I and IV also showed increased secretion of pro-inflammatory cytokines, MCP-1 and IL-8. Nitrite-modification of RPE-secreted ECM (simulating ageing of Bruch's membrane) significantly reduced in vitro RPE attachment to the ECM and this was mitigated with collagen IV coating of the modified ECM. Taken together, our observations confirm the importance of RPE-ECM interactions for normal RPE growth and function, and for inducing RPE secretion of pro-inflammatory cytokines. Furthermore, the findings are consistent with ageing and/or oxidative stress-induced disruption of RPE-ECM interactions contributing to the pathogenesis of AMD.
C1 [Eamegdool, Steven S.; Sitiwin, Ephrem I.; Cioanca, Adrian V.; Madigan, Michele C.] Univ Sydney, Save Sight Inst, Sydney, NSW 2000, Australia.
   [Sitiwin, Ephrem I.; Madigan, Michele C.] UNSW, Sch Optometry & Vis Sci, Sydney, NSW 2052, Australia.
   [Sitiwin, Ephrem I.] Univ New South Wales, Biomed Imaging Facil, Sydney, NSW 2052, Australia.
   [Eamegdool, Steven S.] Childrens Med Res Inst, Eye Genet Res Unit, Westmead, NSW 2145, Australia.
   [Cioanca, Adrian V.] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
C3 University of Sydney; University of New South Wales Sydney; University
   of New South Wales Sydney; Children's Medical Research Institute -
   Australia; Australian National University; John Curtin School of Medical
   Research
RP Eamegdool, SS (通讯作者)，Childrens Med Res Inst, Eye Genet Res Unit, Westmead, NSW 2145, Australia.
EM seamegdool@cmri.org.au; efroix@gmail.com; valerin.cioanca@anu.edu.au;
   michele.madigan@sydney.edu.au
RI Eamegdool, Steven/AAT-5228-2020
OI Cioanca, Adrian/0000-0003-1379-9993
FU National Foundation for Medical Research and Innovation (NFMRI); Claffy
   Foundation
FX This work was supported in part by The National Foundation for Medical
   Research and Innovation (NFMRI) (MCM) and The Claffy Foundation (SSE).
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NR 82
TC 16
Z9 16
U1 3
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JAN
PY 2020
VL 146
BP 357
EP 371
DI 10.1016/j.freeradbiomed.2019.11.018
PG 15
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA JZ1LS
UT WOS:000504866900031
PM 31751761
DA 2022-11-30
ER

PT J
AU Nivison-Smith, L
   Milston, R
   Chiang, J
   Ly, A
   Assaad, N
   Kalloniatis, M
AF Nivison-Smith, Lisa
   Milston, Rebecca
   Chiang, Jaclyn
   Ly, Angelica
   Assaad, Nagi
   Kalloniatis, Michael
TI Peripheral retinal findings in populations with macular disease are
   similar to healthy eyes
SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS
LA English
DT Article
DE macular disease; peripheral retina; ultra-widefield imaging
ID WIDEFIELD FLUORESCEIN ANGIOGRAPHY; DIABETIC-RETINOPATHY; COLLABORATIVE
   CARE; AUTOFLUORESCENCE; MANAGEMENT; LESIONS; QUANTIFICATION;
   ABNORMALITIES; PREVALENCE; GENOTYPES
AB Purpose Recent evidence suggests several macular diseases are associated with peripheral retinal changes. This study investigated the number, type and management consequences of peripheral retinal findings detected in patients attending a referral only, eye-care clinic, the Centre for Eye Health(CFEH) with macular disease. Methods Records of 537 patients attending CFEH for a macular assessment were included in the study. Subjects were classified as having age-related macular degeneration (AMD), epiretinal membrane (ERM), central serous chorioretinopathy (CSCR), inherited macular dystrophy or no macular disease. Data extracted included reason for referral, macular findings, peripheral findings (based on examination by ultra-widefield scanning laser ophthalmoscopy), diagnosis and management. Results After age-matching, the number of peripheral findings in subjects with AMD, ERM or CSCR was not significant different to normal subjects. The most common finding for all cohorts were non-specific, degenerative changes such as drusen or pigmentation (61-72%) except inherited macular dystrophy subjects who had mostly vascular findings (30%; p < 0.05). Subjects with AMD and ERM with peripheral findings were significantly more likely to be reviewed or referred to an ophthalmologist than discharged back to their community eye care provider compared to subjects without findings. However only 8% of subjects had altered management based specifically on peripheral findings suggesting the macular findings in most subjects dictated their management. For those with a change, it was significant (upgrade to referral to an ophthalmologist). Peripheral findings also flagged 5% of subjects with vascular findings for referral to their general practitioner (GP). Conclusions Overall, the percentage and distribution of peripheral retinal findings in some macular diseases was similar to normal subjects. However, subjects with peripheral findings appeared to have significant differences in management. Considering some common findings, such as peripheral drusen may be relevant to AMD pathogenesis and therefore affect management of this disease, assessment of the peripheral retina should not be overlooked when the clinical focus is on the posterior pole.
C1 [Nivison-Smith, Lisa; Milston, Rebecca; Chiang, Jaclyn; Ly, Angelica; Assaad, Nagi; Kalloniatis, Michael] Univ New South Wales, Ctr Eye Hlth, Sydney, NSW, Australia.
   [Nivison-Smith, Lisa; Ly, Angelica; Kalloniatis, Michael] Univ New South Wales, Sch Optometry & Vis Sci, Sydney, NSW, Australia.
   [Assaad, Nagi] Prince Wales Hosp, Dept Ophthalmol, Randwick, NSW, Australia.
C3 University of New South Wales Sydney; University of New South Wales
   Sydney
RP Nivison-Smith, L (通讯作者)，Univ New South Wales, Ctr Eye Hlth, Sydney, NSW, Australia.; Nivison-Smith, L (通讯作者)，Univ New South Wales, Sch Optometry & Vis Sci, Sydney, NSW, Australia.
EM l.nivison-smith@unsw.edu.au
OI Ly, Angelica/0000-0001-7881-1522; Nivison-Smith,
   Lisa/0000-0001-6677-1949; Kalloniatis, Michael/0000-0002-5264-4639
FU National Health and Medical Research Council of Australia [1033224];
   University of New South Wales [2015/6]
FX This work was supported in part by research grants from the National
   Health and Medical Research Council of Australia (#1033224) and the
   University of New South Wales (Early Career Research Grant 2015/6 and a
   Research Training Program stipend). The Centre for Eye Health is an
   initiative between UNSW Australia and Guide Dogs NSW/ACT. Guide Dogs
   NSW/ACT is also a partner on the NHMRC grant and also provided a
   supplementary PhD scholarship for AL and support for LN-S.
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NR 48
TC 6
Z9 7
U1 0
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-5408
EI 1475-1313
J9 OPHTHAL PHYSL OPT
JI Ophthalmic Physiol. Opt.
PD NOV
PY 2018
VL 38
IS 6
BP 584
EP 595
DI 10.1111/opo.12589
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HF2TB
UT WOS:000454088200003
PM 30575075
OA Green Published
DA 2022-11-30
ER

PT J
AU Zareba, M
   Widomska, J
   Burke, JM
   Subczynski, WK
AF Zareba, M.
   Widomska, J.
   Burke, J. M.
   Subczynski, W. K.
TI Nitroxide free radicals protect macular carotenoids against chemical
   destruction (bleaching) during lipid peroxidation
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Zeaxanthin; Carotenoid; Oxidative stress; Lipid peroxidation;
   Antioxidants; AMD
ID SINGLET MOLECULAR-OXYGEN; BETA-CAROTENE; FATTY-ACIDS; ZEAXANTHIN;
   LUTEIN; XANTHOPHYLLS; CHOLESTEROL; PIGMENT; LIGHT; ANTIOXIDANTS
AB Macular xanthophylls (MXs) lutein and zeaxanthin are dietary carotenoids that are selectively concentrated in the human eye retina, where they are thought to protect against age-related macular degeneration (AMD) by multiple mechanisms, including filtration of phototoxic blue light and quenching of singlet oxygen and triplet states of photosensitizers. These physical protective mechanisms require that MXs be in their intact structure. Here, we investigated the protection of the intact structure of zeaxanthin incorporated into model membranes subjected to oxidative modification by water-and/or membrane-soluble small nitroxide free radicals. Model membranes were formed from saturated, monounsaturated, and polyunsaturated phosphatidylcholines (PCs). Oxidative modification involved autoxidation, iron-mediated, and singlet oxygen-mediated lipid peroxidation. The extent of chemical destruction (bleaching) of zeaxanthin was evaluated from its absorption spectra and compared with the extent of lipid peroxidation evaluated using the thiobarbituric acid assay. Nitroxide free radicals with different polarity (membrane/water partition coefficients) were used. The extent of zeaxanthin bleaching increased with membrane unsaturation and correlated with the rate of PC oxidation. Protection of the intact structure of zeaxanthin by membrane-soluble nitroxides was much stronger than that by water-soluble nitroxides. The combination of zeaxanthin and lipid-soluble nitroxides exerted strong synergistic protection against singlet oxygen-induced lipid peroxidation. The synergistic effect may be explained in terms of protection of the intact zeaxanthin structure by effective scavenging of free radicals by nitroxides, therefore allowing zeaxanthin to quench the primary oxidant, singlet oxygen, effectively by the physical protective mechanism. The redox state of nitroxides was monitored using electron paramagnetic resonance spectroscopy. Both nitroxide free radicals and their reduced form, hydroxylamines, were equally effective. Obtained data were compared with the protective effects of a-tocopherol, which is the natural antioxidant and protector of MXs within the retina. The new strategies employed here to maintain the intact structure of MXs may enhance their protective potential against AMD.
C1 [Zareba, M.; Subczynski, W. K.] Med Coll Wisconsin, Dept Biophys, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
   [Zareba, M.; Burke, J. M.] Med Coll Wisconsin, Dept Ophthalmol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
   [Widomska, J.] Med Univ Lublin, Dept Biophys, Aleje Raclawickie 1, Lublin, Poland.
C3 Medical College of Wisconsin; Medical College of Wisconsin; Medical
   University of Lublin
RP Subczynski, WK (通讯作者)，Med Coll Wisconsin, Dept Biophys, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM subczyn@mcw.edu
OI Widomska, Justyna/0000-0003-2358-4099
FU NATIONAL EYE INSTITUTE [P30EY001931, R01EY015526] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
   [P41EB001980] Funding Source: NIH RePORTER; NEI NIH HHS [R01 EY015526,
   P30 EY001931] Funding Source: Medline; NIBIB NIH HHS [P41 EB001980]
   Funding Source: Medline
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NR 74
TC 11
Z9 11
U1 1
U2 29
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD DEC
PY 2016
VL 101
BP 446
EP 454
DI 10.1016/j.freeradbiomed.2016.11.012
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA EG0DN
UT WOS:000390701300041
PM 27840316
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Islam, FMA
   Chakrabarti, R
   Islam, SZ
   Finger, RP
   Critchley, C
AF Islam, Fakir M. Amirul
   Chakrabarti, Rahul
   Islam, Silvia Z.
   Finger, Robert P.
   Critchley, Christine
TI Factors Associated with Awareness, Attitudes and Practices Regarding
   Common Eye Diseases in the General Population in a Rural District in
   Bangladesh: The Bangladesh Population-based Diabetes and Eye Study
   (BPDES)
SO PLOS ONE
LA English
DT Article
ID LOW-VISION SURVEY; NATIONAL BLINDNESS; RISK-FACTORS; KNOWLEDGE;
   RETINOPATHY; PREVALENCE; ADULTS; HEALTH; INDIA; COMMUNITY
AB Background
   To assess the awareness, attitudes, and practices associated with common eye diseases and eye care utilization in a rural district of Bangladesh.
   Methods
   Data were collected using a multilevel cluster random sampling technique from 3104 adults aged >= 30 years from the Banshgram union with a questionnaire assessing the awareness, attitudes and practice about diabetes and common eye diseases, educational attainment, socio-economic status, and medical history.
   Results
   Participants were aged between 30 and 89 years with a mean (SD) age of 51 (12) years and 65% were female. The majority of participants had heard of cataracts (90%), trachoma (86%) and Pterygium (84%), yet only 4% had heard of diabetic retinopathy (DR), 7% of glaucoma and 8% of Age-related macular degeneration (AMD). However, 58% of participants did not know vision loss could be prevented. Factors associated with lower awareness regarding common eye diseases were increasing age, lack of formal schooling, and lower socio-economic status. A lower proportion (57%) of people with no schooling compared to those who had attained at least secondary school certificate education (72%) reported that they knew that vision loss could be prevented (p<0.001). Overall 51% of people had heard of at least six (67%) out of nine items relating to awareness of common eye diseases. This included 41% of participants aged 65 years or older compared to 61% of those aged 30-35 years (p<0.001). Only 4% had an eye check at least once a year and higher education and better SES were associated with higher frequency of eye checks.
   Conclusions
   In rural Bangladesh awareness of cataract, trachoma and pterygium was good but limited in relation to the potentially blinding conditions of glaucoma, DR, and AMD. The results show a large gap between public awareness and treatment practices about common eye diseases. Public health promotion should be designed to address these knowledge gaps.
C1 [Islam, Fakir M. Amirul; Critchley, Christine] Swinburne Univ Technol, Dept Stat Data Sci & Epidemiol, Hawthorn, Vic 3122, Australia.
   [Islam, Fakir M. Amirul; Chakrabarti, Rahul; Islam, Silvia Z.] Org Rural Community Dev, Dariapur, Narail, Bangladesh.
   [Chakrabarti, Rahul; Finger, Robert P.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Islam, Silvia Z.] RMIT Univ Technol, Sch Econ Finance & Mkt, Melbourne, Vic, Australia.
C3 Swinburne University of Technology; Centre for Eye Research Australia;
   Royal Victorian Eye & Ear Hospital; University of Melbourne; Royal
   Melbourne Institute of Technology (RMIT)
RP Islam, FMA (通讯作者)，Swinburne Univ Technol, Dept Stat Data Sci & Epidemiol, Hawthorn, Vic 3122, Australia.
EM fislam@swin.edu.au
RI Islam, Fakir M Amirul/P-6665-2015
OI Islam, Fakir M Amirul/0000-0003-3897-3302; Finger, Robert
   P/0000-0003-4253-7597
CR Aitaoto Nia, 2012, Prev Chronic Dis, V9, pE82
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NR 31
TC 37
Z9 37
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 22
PY 2015
VL 10
IS 7
AR e0133043
DI 10.1371/journal.pone.0133043
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CN7EO
UT WOS:000358597100051
PM 26200458
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sasore, T
   Kennedy, B
AF Sasore, Temitope
   Kennedy, Breandan
TI Deciphering Combinations of PI3K/AKT/mTOR Pathway Drugs Augmenting
   Anti-Angiogenic Efficacy In Vivo
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; RENAL-CELL
   CARCINOMA; MACULAR DEGENERATION; PHOSPHOINOSITIDE 3-KINASE; INTRAVITREAL
   INJECTION; VISUAL FUNCTION; ZEBRAFISH; EXPRESSION; VEGF
AB Ocular neovascularization is a common pathology associated with human eye diseases e.g. age-related macular degeneration and proliferative diabetic retinopathy. Blindness represents one of the most feared disabilities and remains a major burden to health-care systems. Current approaches to treat ocular neovascularisation include laser photocoagulation, photodynamic therapy and anti-VEGF therapies: Ranibizumab (Lucentis) and Aflibercept (Eylea). However, high clinical costs, frequent intraocular injections, and increased risk of infections are challenges related with these standards of care. Thus, there is a clinical need to develop more effective drugs that overcome these challenges. Here, we focus on an alternative approach by quantifying the in vivo anti-angiogenic efficacy of combinations of phosphatidylinositol-3-kinase (PI3K) pathway inhibitors. The PI3K/AKT/mTOR pathway is a complex signalling pathway involved in crucial cellular functions such as cell proliferation, migration and angiogenesis. RT-PCR confirms the expression of PI3K target genes (pik3ca, pik3r1, mtor and akt1) in zebrafish trunks from 6 hours post fertilisation (hpf) and in eyes from 2 days post fertilisation (dpf). Using both the zebrafish intersegmental vessel and hyaloid vessel assays to measure the in vivo anti-angiogenic efficacy of PI3K/Akt/mTOR pathway inhibitors, we identified 5 mu M combinations of i) NVP-BEZ235 (dual PI3K-mTOR inhibitor) + PI-103 (dual PI3K-mTOR inhibitor); or ii) LY-294002 (pan-PI3K inhibitor) + NVP-BEZ235; or iii) NVP-BEZ235 + rapamycin (mTOR inhibitor); or iv) LY-294002 + rapamycin as the most anti-angiogenic. Treatment of developing larvae from 2-5 dpf with 5 mu M NVP-BEZ235 plus PI-103 resulted in an essentially intact ocular morphology and visual behaviour, whereas other combinations severely disrupted the developing retinal morphology and visual function. In human ARPE19 retinal pigment epithelium cells, however, no significant difference in cell number was observed following treatment with the inhibitor combinations. Collectively, these results highlight the potential of combinations of PI3K/AKT/mTOR pathway inhibitors to safely and effectively treat ocular neovascularization.
C1 [Sasore, Temitope; Kennedy, Breandan] Univ Coll Dublin, UCD Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin 2, Ireland.
C3 University College Dublin
RP Kennedy, B (通讯作者)，Univ Coll Dublin, UCD Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin 2, Ireland.
EM brendan.kennedy@ucd.ie
RI kennedy, Breandan/H-5643-2019
OI kennedy, Breandan/0000-0001-7991-4689
FU Irish Research Council; Marie Curie Actions- Industry-Academia
   Partnerships and Pathways (IAPP) [612218 (3D-NET)]
FX This research was supported by an Irish Research Council postgraduate
   scholarship (TS) and a Marie Curie Actions- Industry-Academia
   Partnerships and Pathways (IAPP) grant #612218 (3D-NET) (BK). The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
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NR 55
TC 31
Z9 32
U1 3
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 21
PY 2014
VL 9
IS 8
AR e105280
DI 10.1371/journal.pone.0105280
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AO1WL
UT WOS:000341106100046
PM 25144531
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Cao, SJ
   Walker, GB
   Wang, XF
   Cui, JZ
   Matsubara, JA
AF Cao, Sijia
   Walker, Gregory B.
   Wang, Xuefeng
   Cui, Jing Z.
   Matsubara, Joanne A.
TI Altered cytokine profiles of human retinal pigment epithelium: Oxidant
   injury and replicative senescence
SO MOLECULAR VISION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; OXIDATIVE STRESS;
   GENE-EXPRESSION; MICROARRAY ANALYSIS; CELLS; DRUSEN; RPE; EYE;
   HISTOCHEMISTRY
AB Purpose: Age-related macular degeneration (AMD) is a local, chronic inflammatory disease of the eye that is influenced by oxidative stress and dysregulation of the retinal pigment epithelium (RPE) associated with aging. The purpose of this study is to characterize the effects of oxidative stress and replicative senescence on the secreted cytokine profiles of RPE in vitro.
   Methods: We used multiple, serial passages of human RPE cells from primary culture as an in vitro model of aging. Responses of early passage 5 (P5) and late passage 21 (P21) RPE cells were compared. Oxidative stress was induced in RPE cells (P5) by exposure to 75 mu M hydroquinone (HQ) for 24 h. The secretome profiles of the RPE cells were measured with a multiplex suspension assay that assayed human cytokine, chemokine, and growth factors. Immunohistochemistry on younger (<= 55 years old) and older (>= 70 years old) human post-mortem donor eyes was used to verify selected cytokines.
   Results: Supernatant of HQ-treated RPE cultures exhibited increased secreted levels of vascular endothelial growth factor (VEGF), interleukin (IL)-12, and IL-10 that reached statistical significance (p<0.05). Supernatant of late passage P21 RPE cultures exhibited decreased secreted levels of stromal cell-derived factor (SDF)-1 alpha, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-8, IL-15, IL-6, and an increased level of IL-1ra compared to early passage P5 RPE cultures that reached statistical significance (p<0.05). Immunohistochemical analysis demonstrated incre
   Conclusions: Our data demonstrate a unique cytokine secretion profile of primary culture RPE cells at early and late passage. Our in vitro data suggest an age-specific modulation of cytokine secretion in RPE and is consistent with immunohistochemical analysis on post-mortem eyes. The secretion profile associated with RPE under conditions that mimic oxidative stress, another factor associated with the pathogenesis of AMD, emphasizes upregulation of the angiogenic growth factor, vascular endothelial growth factor. Together, these data support the role of advanced age and oxidative stress in inflammatory cytokine modulation in RPE cells.
C1 [Matsubara, Joanne A.] Eye Care Ctr, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 3N9, Canada.
   [Cao, Sijia; Walker, Gregory B.; Wang, Xuefeng; Cui, Jing Z.; Matsubara, Joanne A.] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada.
C3 University of British Columbia; University of British Columbia
RP Matsubara, JA (通讯作者)，Eye Care Ctr, Dept Ophthalmol & Visual Sci, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada.
EM jms@mail.ubc.ca
FU CIHR [IAO 77,736, MOP 97,806]
FX We thank Eleanor To and Orson L. Moritz of Department of Ophthalmology,
   UBC for their technical assistance and advice throughout the study. This
   study was supported by CIHR (IAO 77,736 & MOP 97,806 to JAM). The
   authors have no proprietary or commercial interest in any materials
   discussed in this article. Part of this work was presented at 2010 ARVO
   program#6164 [45].
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NR 45
TC 43
Z9 44
U1 3
U2 5
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD MAR 21
PY 2013
VL 19
BP 718
EP 728
PG 11
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 110BQ
UT WOS:000316417500009
PM 23559866
DA 2022-11-30
ER

PT J
AU Losonczy, G
   Vajas, A
   Takacs, L
   Dzsudzsak, E
   Fekete, A
   Marhoffer, E
   Kardos, L
   Ajzner, E
   Hurtado, B
   de Frutos, PG
   Berta, A
   Balogh, I
AF Losonczy, Gergely
   Vajas, Attila
   Takacs, Lili
   Dzsudzsak, Erika
   Fekete, Agnes
   Marhoffer, Eva
   Kardos, Laszlo
   Ajzner, Eva
   Hurtado, Begona
   Garcia de Frutos, Pablo
   Berta, Andras
   Balogh, Istvan
TI Effect of the Gas6 c.834+7G > A Polymorphism and the Interaction of
   Known Risk Factors on AMD Pathogenesis in Hungarian Patients
SO PLOS ONE
LA English
DT Article
ID COMPLEMENT FACTOR-H; HTRA1 PROMOTER POLYMORPHISM; AGE-RELATED
   MACULOPATHY; APOLIPOPROTEIN-E GENE; MACULAR DEGENERATION; FACTOR-XIII;
   DRUSEN FORMATION; FACTOR-I; VARIANT; SUSCEPTIBILITY
AB Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. Numerous genetic factors contribute to the development of the multifactorial disease. We performed a case-control study to assess the risk conferred by known and candidate genetic polymorphisms on the development of AMD. We searched for genetic interactions and for differences in dry and wet AMD etiology. We enrolled 213 patients with exudative, 67 patients with dry AMD and 106 age and ethnically matched controls. Altogether 12 polymorphisms in Apolipoprotein E, complement factor H, complement factor I, complement component 3, blood coagulation factor XIII, HTRA1, LOC387715, Gas6 and MerTK genes were tested. No association was found between either the exudative or the dry form and the polymorphisms in the Apolipoprotein E, complement factor I, FXIII and MerTK genes. Gas6 c. 834+7G>A polymorphism was found to be significantly protective irrespective of other genotypes, reducing the odds of wet type AMD by a half (OR = 0.50, 95% CI: 0.26-0.97, p = 0.04). Multiple regression models revealed an interesting genetic interaction in the dry AMD subgroup. In the absence of C3 risk allele, mutant genotypes of both CFH and HTRA1 behaved as strongly significant risk factors (OR = 7.96, 95% CI: 2.39 = 26.50, p = 0.0007, and OR = 36.02, 95% CI: 3.30-393.02, p = 0.0033, respectively), but reduced to neutrality otherwise. The risk allele of C3 was observed to carry a significant risk in the simultaneous absence of homozygous CFH and HTRA1 polymorphisms only, in which case it was associated with a near-five-fold relative increase in the odds of dry type AMD (OR = 4.93, 95% CI: 1.98-12.25, p = 0.0006). Our results suggest a protective role of Gas6 c. 834+7G>A polymorphism in exudative AMD development. In addition, novel genetic interactions were revealed between CFH, HTRA1 and C3 polymorphisms that might contribute to the pathogenesis of dry AMD.
C1 [Losonczy, Gergely; Vajas, Attila; Takacs, Lili; Marhoffer, Eva; Berta, Andras] Univ Debrecen, Dept Ophthalmol, H-4012 Debrecen, Hungary.
   [Dzsudzsak, Erika; Balogh, Istvan] Univ Debrecen, Dept Lab Med, H-4012 Debrecen, Hungary.
   [Fekete, Agnes] Univ Debrecen, Dept Anesthesiol & Intens Care, H-4012 Debrecen, Hungary.
   [Kardos, Laszlo] Kenezy Gyula Cty Hosp, Hyg & Infect Control Serv, Debrecen, Hungary.
   [Ajzner, Eva] Josa Andras Teaching Hosp, Cent Lab, Nyiregyhaza, Hungary.
   [Hurtado, Begona; Garcia de Frutos, Pablo] Inst Biomed Res Barcelona IIBB CSIC, IDIBAPS, Dept Cell Death & Proliferat, Barcelona, Spain.
C3 University of Debrecen; University of Debrecen; University of Debrecen;
   Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto
   de Investigaciones Biomedicas de Barcelona (IIBB); University of
   Barcelona; Hospital Clinic de Barcelona; IDIBAPS
RP Losonczy, G (通讯作者)，Univ Debrecen, Dept Ophthalmol, H-4012 Debrecen, Hungary.
EM losigeri@gmail.com
RI Vajas, Attila/AAA-3014-2021; de Frutos, Pablo García/B-8594-2011;
   Takács, Lili/L-6660-2014; Balogh, Istvan/N-2990-2019; Balogh,
   Istvan/A-4752-2013
OI de Frutos, Pablo García/0000-0003-1547-1190; Takács,
   Lili/0000-0003-1641-0154; Balogh, Istvan/0000-0003-3397-2829; Balogh,
   Istvan/0000-0003-3397-2829
FU Hungarian Research Fund OTKA [K68616]; Social Renewal Operational
   Programme TAMOP [4.2.1./B-091/1/KONV-2010-0007]
FX This study was supported by by the Hungarian Research Fund OTKA K68616
   (to A.B.) and by the Social Renewal Operational Programme TAMOP
   4.2.1./B-091/1/KONV-2010-0007 project (to A.B. and I.B.). The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
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NR 64
TC 5
Z9 6
U1 0
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 29
PY 2012
VL 7
IS 11
AR e50181
DI 10.1371/journal.pone.0050181
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 051DI
UT WOS:000312104900032
PM 23209669
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Palmer, S
   Logan, D
   Nabili, S
   Dutton, GN
AF Palmer, Shelagh
   Logan, David
   Nabili, Shahriar
   Dutton, Gordon N.
TI Effective rehabilitation of reading by training in the technique of
   eccentric viewing: evaluation of a 4-year programme of service delivery
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DISEASE; RETINAL LOCUS; CENTRAL SCOTOMA; DEGENERATION
AB Background/aims Central visual loss caused by conditions such as age-related macular degeneration (ARMD) is the commonest cause of blindness in the UK. Eccentric viewing training aims to teach patients how to utilise the functioning areas of macula or adjacent retina and establish a 'pseudofovea'. This technique has yet to gain acceptance in the UK despite evidence of success. Subjects with ARMD in Glasgow, UK, have received such training, and the outcome of training for this group is described.
   Methods Retrospective analysis auditing the outcome of eccentric viewing training to read was carried out in 300 subjects with ARMD.
   Results The data for 300 patients were reviewed. Fifty-eight subjects were excluded due to incomplete final data. Reading speed, font size, degree of comprehension, duration of reading, and age and number of lessons were recorded before and after training. The mean age was 75.4 (SD 12). The mean number of 1-h lessons required was 3.8 (SD 1.6). The starting mean number of corrected words per min (WPM) reading speed was 48 (SD 35) and this increased to 71.9 (SD 30.5) (p=0.000). The starting Arial font size that could be read fluently was 14.3 (SD 7.6) and this improved to 11.5 (SD 2.4). The starting mean duration of comfortable reading was 1.7 (SD 2.0) min. This increased to 15.8 (SD 14.6) min. The mean percentage of material read that was understood by the patients was 73.7 (SD 36.9)%. This improved to 92.7 (SD 16.2)% (p=0.000). Overall, the majority of patients exhibited improvement in one or more of the vision-related tasks measured.
   Conclusion Eccentric viewing training is successful in improving the reading ability of individuals with a central scotoma. This paper shows evidence of the success of training provided by the voluntary sector and funded by adult literacy funding. The results are comparable with those reported in the literature.
C1 [Nabili, Shahriar; Dutton, Gordon N.] Gartnavel Royal Hosp, Tennent Inst Ophthalmol, Glasgow G12 0YN, Lanark, Scotland.
   [Palmer, Shelagh; Logan, David] Visibility, Glasgow, Lanark, Scotland.
   [Dutton, Gordon N.] Glasgow Caledonian Univ, Dept Vis Sci, Glasgow G4 0BA, Lanark, Scotland.
   [Dutton, Gordon N.] Royal Hosp Sick Children, Glasgow G3 8SJ, Lanark, Scotland.
C3 Gartnavel Royal Hospital; Glasgow Caledonian University; University of
   Glasgow
RP Nabili, S (通讯作者)，Gartnavel Royal Hosp, Tennent Inst Ophthalmol, Great Western Rd, Glasgow G12 0YN, Lanark, Scotland.
EM nabili@hotmail.com
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NR 16
TC 22
Z9 23
U1 0
U2 11
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD APR
PY 2010
VL 94
IS 4
BP 494
EP 497
DI 10.1136/bjo.2008.152231
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 585QL
UT WOS:000276841900021
PM 19822918
DA 2022-11-30
ER

PT J
AU Forrester, JV
   Xu, HP
   Kuffova, L
   Dick, AD
   McMenamin, PG
AF Forrester, John V.
   Xu, Heping
   Kuffova, Lucia
   Dick, Andrew D.
   McMenamin, Paul G.
TI Dendritic cell physiology and function in the eye
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE dendritic cells; tolerance; autoimmunity; cell trafficking; in vivo
   imaging; transplantation
ID REGULATORY T-CELLS; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS;
   RESIDENT-TISSUE MACROPHAGES; CORNEAL EPITHELIAL-CELLS;
   ANTIGEN-PRESENTING CELLS; MHC CLASS-II; EXPERIMENTAL ALLERGIC UVEITIS;
   DRAINING LYMPH-NODES; TOLL-LIKE RECEPTORS; IN-VIVO
AB The eye and the brain are immunologically privileged sites, a property previously attributed to the lack of a lymphatic circulation. However, recent tracking studies confirm that these organs have good communication through classical site-specific lymph nodes, as well as direct connection through the blood circulation with the spleen. In addition, like all tissues, they contain resident myeloid cell populations that play important roles in tissue homeostasis and the response to foreign antigens. Most of the macrophage and dendritic cell (DC) populations in the eye are restricted to the supporting connective tissues, including the cornea, while the neural tissue (the retina) contains almost no DCs, occasional macrophages (perivascularly distributed), and a specialized myeloid cell type, the microglial cell. Resident microglial cells are normally programmed for immunological tolerance. The privileged status of the eye, however, is relative, as it is susceptible to immune-mediated inflammatory disease, both infectious and autoimmune. Intraocular inflammation (uveitis and uveoretinitis) and corneal graft rejection constitute two of the more common inflammatory conditions affecting the eye leading to considerable morbidity (blindness). As corneal graft rejection occurs almost exclusively by indirect allorecognition, host DCs play a major role in this process and are likely to be modified in their behavior by the ocular microenvironment. Ocular surface disease, including allergy and atopy, also comprise a significant group of immune-mediated eye disorders in which DCs participate, while infectious disease such as herpes simplex keratitis is thought to be initiated via corneal DCs. Intriguingly, some more common conditions previously thought to be degenerative (e.g. age-related macular degeneration) may have an autoimmune component in which ocular DCs and macrophages are critically involved. Recently, the possibility of harnessing the tolerizing potential of DCs has been applied to experimental models of autoimmune uveoretinitis with good effect. This approach has considerable potential for use in translational clinical therapy to prevent sight-threatening disease caused by ocular inflammation.
C1 [Forrester, John V.; Xu, Heping; Kuffova, Lucia] Univ Aberdeen, Sect Immunol & Infect, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
   [Dick, Andrew D.] Univ Bristol, Dept Cellular & Mol Med, Bristol, Avon, England.
   [McMenamin, Paul G.] Univ Western Australia, Dept Anat & Human Biol, Perth, WA 6009, Australia.
C3 University of Aberdeen; University of Bristol; University of Western
   Australia
RP Forrester, JV (通讯作者)，Univ Aberdeen, Sect Immunol & Infect, Inst Med Sci, Foresterhill, Aberdeen AB25 2ZD, Scotland.
EM j.forrester@abdn.ac.uk
RI Xu, Heping/A-4430-2008
OI Xu, Heping/0000-0003-4000-931X; Dick, Andrew/0000-0002-0742-3159;
   McMenamin, Paul/0000-0002-7141-1283
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NR 191
TC 140
Z9 148
U1 0
U2 17
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
EI 1600-065X
J9 IMMUNOL REV
JI Immunol. Rev.
PD MAR
PY 2010
VL 234
BP 282
EP 304
DI 10.1111/j.0105-2896.2009.00873.x
PG 23
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 559HC
UT WOS:000274813200019
PM 20193026
DA 2022-11-30
ER

PT J
AU Nazari, H
   ModarresZadeh, M
   Bahmani-Kashkouli, M
   Naseripour, M
   Parvaresh, MM
   Nazari, P
AF Nazari, Hossein
   ModarresZadeh, Mehdi
   Bahmani-Kashkouli, Mohsen
   Naseripour, Masoud
   Parvaresh, Mohamtnad-Mehdi
   Nazari, Paridokht
TI Central Retinal Artery Perfusion following 0.1 ml Intravitreal Injection
   of Bevacizumab
SO IRANIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Intravitreal Injection; Central Retinal Artery; Intraocular Pressure
ID DIABETIC MACULAR EDEMA; ANTERIOR-CHAMBER PARACENTESIS; TRIAMCINOLONE
   ACETONIDE; INTRAOCULAR-PRESSURE; VEIN OCCLUSION; CHOROIDAL
   NEOVASCULARIZATION; DEGENERATION; NECESSITY; THERAPY; AVASTIN
AB Purpose: To study the pattern of perfusion of central retinal artery (CRA) after 0.1 ml intravitreal injection of bevacizumab to verify the need for any maneuver to decrease the intraocular pressure (IOP) including anterior chamber paracentesis (ACP)
   Methods: This is a prospective, interventional, noncomparative case series. Patients receiving intravitreal injection of bevacizumab for choroidal neovascularization (CNV) secondary to age-related macular degeneration, diabetic macular edema and retinal veno-occlusive diseases were included in the study. Each eye received 0.1 ml intravitreal injection of bevacizumab and the status of perfusion of CRA and its pulsation was monitored by indirect ophthalmoscopy until cessation of visible pulsation. Main outcome measures were patency of CRA, its pulsation and time from injection to cessation of pulsation.
   Results: Seventy seven eyes of 70 patients were studied. At first ophthalmoscopy 30 seconds after injection, CRA was open in all cases with or without pulsation. CRA occlusion was not observed in any case. In 20 eyes (26%) CRA was patent without pulsation. In 57 eyes (74%) CRA pulsation was detected and this visible pulsation of CRA stopped within an average time of 167 99 seconds (range: 30-480 seconds). From 17 eyes which had significant vitreous reflux, only 6 eyes had CRA pulsation which stopped in a mean time of 80 36 seconds. There was a significant difference between pulsation duration in patients with and without vitreous reflux (Mann-Whitney U test, P=0.005). Absence of postinjection vitreous reflux was a risk factor for CRA pulsation after intravitreal injection of 0.1 ml of bevacizumab (relative risk: 2.41, 95% CI: 1.25-4.62).
   Conclusion: Considering the absence of CRA closure and the short time needed for the cessation of pulsation after intravitreal injection of 0.1 ml bevacizumab, no treatment including ACP is warranted before or after such injections in nonglaucomatous eyes. Indirect ophthalmoscopy is a noninvasive useful maneuver to ascertain patency of CRA after intravitreal injections.
C1 [Nazari, Hossein; ModarresZadeh, Mehdi; Bahmani-Kashkouli, Mohsen; Naseripour, Masoud; Parvaresh, Mohamtnad-Mehdi; Nazari, Paridokht] Iran Univ Med Sci, Eye Res Ctr, Rassoul Akram Hosp, Tehran, Iran.
C3 Iran University of Medical Sciences
RP Nazari, H (通讯作者)，Iran Univ Med Sci, Eye Res Ctr, Rassoul Akram Hosp, Tehran, Iran.
EM h01nazari@yahoo.com
RI Nazari, Hossein/GOK-8161-2022; Naseripour, Masood/A-6998-2018;
   Naseripour, Masood/P-8976-2018; Kashkouli, Mohsen B/G-1119-2011
OI Nazari, Hossein/0000-0002-8945-9680; Naseripour,
   Masood/0000-0003-1217-3470; Kashkouli, Mohsen B/0000-0003-0347-5549
FU Iran University Eye Research Center, Tehran, Iran
FX This study was conducted with support of Iran University Eye Research
   Center, Tehran, Iran
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TC 0
Z9 0
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PU IRANIAN SOC OPHTHALMOLOGY
PI TEHRAN
PA NORTH KARGAR AVE, 2ND FLR, NO 4, HOMA ALLEY, TEHRAN, 1418654743, IRAN
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J9 IRAN J OPHTHALMOL
JI Iran. J. Ophthalmol.
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IS 2
BP 13
EP 18
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 581JG
UT WOS:000276518000003
DA 2022-11-30
ER

PT J
AU Iriyama, A
   Chen, YN
   Tamaki, Y
   Yanagi, Y
AF Iriyama, Aya
   Chen, Yi-Ning
   Tamaki, Yasuhiro
   Yanagi, Yasuo
TI Effect of anti-VEGF antibody on retinal ganglion cells in rats
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID INTRAVITREAL BEVACIZUMAB AVASTIN; MACULAR DEGENERATION; INDOCYANINE
   GREEN; PENETRATION; INJECTION; DISEASE; SAFETY; DAMAGE; EYES
AB Aim: Intravitreal injection of anti-vascular endothelial growth factor ( VEGF) antibody (bevacizumab, Avastin) has become one of the chief choices for the treatment of macular oedema and neovascular age-related macular degeneration. However, the effect of blocking the VEGF function has not been thoroughly explored in vivo. A previous study has reported that intravitreal injection of bevacizumab had no retinal toxicity on rats; however, bevacizumab is human-specific and does not react with rat VEGF. In this study, the authors examined the effect of anti-rat VEGF antibody and bevacizumab on rat retina in vivo and in vitro, especially focusing on retinal ganglion cells (RGCs).
   Methods: In vitro, rat RGCs were purified by a two-step immunopanning procedure, and incubated in the presence of VEGF, bevacizumab, anti-rat VEGF antibody, and control-IgG for three days. The number of viable RGCs was counted. In vivo, after intravitreal injections of bevacizumab, anti-rat VEGF antibody, and control-IgG, viable RGCs were visualised by retrolabelling with Fluo-gold and enumerated to examine the toxicity.
   Results: In vivo, the mean ( standard deviation) number of viable RGCs in the VEGF-treated group (0.99 (0.29) vs control), the bevacizumab-treated group(1.0 (0.23) vs control), the anti-rat VEGF antibody-treated group (0.98 (0.18) vs control) and the control IgG-treated group (0.98 (0.19) vs control) was not statistically different from that of the control group after 3 days. In vitro, the mean (SD) number of viable RGCs in the bevacizumab-treated group (2613 (230)/mm(2)), the anti-rat VEGF antibody-treated group (2600 (140)/mm(2)) and the control IgG-treated group (2656 (150)/mm(2)) was not statistically different from that of the control group (2656 (150)/mm(2)) after 7 days. There were no apparent histological abnormalities.
   Conclusion: This study suggests that bevacizumab and anti-rat VEGF antibody have no short-term, direct retinal toxicity using the rat model. Intravitreal injection of bevacizumab shows no short-term, direct toxicity on RGCs.
C1 Univ Tokyo, Sch Med, Dept Ophthalmol, Bunkyo Ku, Tokyo 1138655, Japan.
C3 University of Tokyo
RP Iriyama, A (通讯作者)，Univ Tokyo, Sch Med, Dept Ophthalmol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM akagi-tky@umin.ac.jp
RI Yanagi, Yasuo/AAA-5441-2022; Yanagi, Yasuo/AAF-2670-2020
OI Yanagi, Yasuo/0000-0002-0362-7285
CR Adamis AP, 2005, RETINA-J RET VIT DIS, V25, P111, DOI 10.1097/00006982-200502000-00001
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NR 18
TC 54
Z9 56
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD SEP
PY 2007
VL 91
IS 9
BP 1230
EP 1233
DI 10.1136/bjo.2007.117309
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 202EN
UT WOS:000248884900036
PM 17475701
OA Green Published
DA 2022-11-30
ER

PT J
AU Stevenson, MR
   Hart, PM
   Chakravarthy, U
   MacKenzie, G
   Bird, AC
   Owens, SL
   Chisholm, IH
   Hall, V
   Houston, RF
   McCulloch, DW
   Plowman, N
AF Stevenson, MR
   Hart, PM
   Chakravarthy, U
   MacKenzie, G
   Bird, AC
   Owens, SL
   Chisholm, IH
   Hall, V
   Houston, RF
   McCulloch, DW
   Plowman, N
TI Visual functioning and quality of life in the SubFoveal Radiotherapy
   Study (SFRADS): SFRADS report 2
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED TRIAL; HEALTH SURVEY SF-36; MACULAR DEGENERATION;
   CATARACT PATIENTS; CLINICAL-TESTS; OUTCOMES; SURGERY; DISABILITY;
   ACUITY; INDEX
AB Aims: To determine whether or not self reported visual functioning and quality of life in patients with choroidal neovascularisation caused by age related macular degeneration (AMD) is better in those treated with 12 Gy external beam radiotherapy in comparison with untreated subjects.
   Methods: A multicentre single masked randomised controlled trial of 12 Gy of external beam radiation therapy (EBRT) delivered as 662 Gy fractions to the macula of an affected eye versus observation. Patients with AMD, aged 60 years or over, in three UK hospital units, who had subfoveal CNV and a visual acuity equal to or better than 6/60 (logMAR 1.0).
   Methods: Data from 199 eligible participants who were randomly assigned to 12 Gy teletherapy or observation were available for analysis. Visual function assessment, ophthalmic examination, and fundus fluorescein angiography were undertaken at baseline and at 3, 6, 12, and 24 months after study entry. To assess patient centred outcomes, subjects were asked to complete the Daily Living Tasks Dependent on Vision (DLTV) and the SF-36 questionnaires at baseline, 6, 12, and 24 months after enrolment to the study. Cross sectional and longitudinal analyses were conducted using arm of study as grouping variable. Regression analysis was employed to adjust for the effect of baseline co-variates on outcome at 12 months and 24 months.
   Results: Both control and treated subjects had significant losses in visual functioning as seen by a progressive decline in mean scores in the four dimensions of the DLTV. There were no statistically significant differences between treatment and control subjects in any of dimensions of the DLTV at 12 months or 24 months after study entry. Regression analysis confirmed that treatment status had no effect on the change in DLTV dimensional scores.
   Conclusions: The small benefits noted in clinical measures of vision in treated eyes did not translate into better self reported visual functioning in patients who received treatment when compared with the control arm. These findings have implications for the design of future clinical trials and studies.
C1 Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland.
   Univ Keele, Ctr Stat, Keele ST5 5BG, Staffs, England.
   UCL, Inst Ophthalmol, London WC1E 6BT, England.
   Southampton Univ Hosp Trust, Eye Unit, Southampton, Hants, England.
   Wessex Radiotherapy Ctr, Southampton, Hants, England.
   No Ireland Radiotherapy Ctr, Belfast, Antrim, North Ireland.
   Univ Ulster, Dept Econ & Polit, Jordanstown, North Ireland.
   St Bartholomews Hosp, Dept Radiat Oncol, London, England.
C3 Queens University Belfast; Keele University; University of London;
   University College London; University of Southampton; University
   Hospital Southampton NHS Foundation Trust; Ulster University; University
   of London; Queen Mary University London
RP Chakravarthy, U (通讯作者)，Royal Hosp, Belfast BT12 6BA, Antrim, North Ireland.
EM u.Chakravarthy@qub.ac.uk
OI Chakravarthy, Usha/0000-0002-2606-3734
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NR 25
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Z9 18
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD AUG
PY 2005
VL 89
IS 8
BP 1045
EP 1051
DI 10.1136/bjo.2003.030445
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 946CK
UT WOS:000230549500031
PM 16024863
OA Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Hoseinzadeh, A
   Johari, HG
   Anbardar, MH
   Tayebi, L
   Vafa, E
   Abbasi, M
   Vaez, A
   Golchin, A
   Amani, AM
   Jangjou, A
AF Hoseinzadeh, Ahmad
   Ghoddusi Johari, Hamed
   Anbardar, Mohammad Hossein
   Tayebi, Lobat
   Vafa, Ehsan
   Abbasi, Milad
   Vaez, Ahmad
   Golchin, Ali
   Amani, Ali Mohammad
   Jangjou, Ali
TI Effective treatment of intractable diseases using nanoparticles to
   interfere with vascular supply and angiogenic process
SO EUROPEAN JOURNAL OF MEDICAL RESEARCH
LA English
DT Review
DE Vascularization; Angiogenesis; Anti-angiogenic therapy; Nanoparticles;
   Therapeutic applications
ID ENDOTHELIAL GROWTH-FACTOR; MAGNETIC-RESONANCE DETECTION; MESENCHYMAL
   STEM-CELLS; THERAPEUTIC ANGIOGENESIS; IN-VIVO; GOLD NANOPARTICLES;
   GENE-THERAPY; TUMOR ANGIOGENESIS; LIMB ISCHEMIA; DRUG-DELIVERY
AB Angiogenesis is a vital biological process involving blood vessels forming from pre-existing vascular systems. This process contributes to various physiological activities, including embryonic development, hair growth, ovulation, menstruation, and the repair and regeneration of damaged tissue. On the other hand, it is essential in treating a wide range of pathological diseases, such as cardiovascular and ischemic diseases, rheumatoid arthritis, malignancies, ophthalmic and retinal diseases, and other chronic conditions. These diseases and disorders are frequently treated by regulating angiogenesis by utilizing a variety of pro-angiogenic or anti-angiogenic agents or molecules by stimulating or suppressing this complicated process, respectively. Nevertheless, many traditional angiogenic therapy techniques suffer from a lack of ability to achieve the intended therapeutic impact because of various constraints. These disadvantages include limited bioavailability, drug resistance, fast elimination, increased price, nonspecificity, and adverse effects. As a result, it is an excellent time for developing various pro- and anti-angiogenic substances that might circumvent the abovementioned restrictions, followed by their efficient use in treating disorders associated with angiogenesis. In recent years, significant progress has been made in different fields of medicine and biology, including therapeutic angiogenesis. Around the world, a multitude of research groups investigated several inorganic or organic nanoparticles (NPs) that had the potential to effectively modify the angiogenesis processes by either enhancing or suppressing the process. Many studies into the processes behind NP-mediated angiogenesis are well described. In this article, we also cover the application of NPs to encourage tissue vascularization as well as their angiogenic and anti-angiogenic effects in the treatment of several disorders, including bone regeneration, peripheral vascular disease, diabetic retinopathy, ischemic stroke, rheumatoid arthritis, post-ischemic cardiovascular injury, age-related macular degeneration, diabetic retinopathy, gene delivery-based angiogenic therapy, protein delivery-based angiogenic therapy, stem cell angiogenic therapy, and diabetic retinopathy, cancer that may benefit from the behavior of the nanostructures in the vascular system throughout the body. In addition, the accompanying difficulties and potential future applications of NPs in treating angiogenesis-related diseases and antiangiogenic therapies are discussed.
C1 [Hoseinzadeh, Ahmad; Ghoddusi Johari, Hamed] Shiraz Univ Med Sci, Thorac & Vasc Surg Res Ctr, Shiraz, Iran.
   [Hoseinzadeh, Ahmad; Ghoddusi Johari, Hamed] Shiraz Univ Med Sci, Sch Med, Namazi Teaching Hosp, Dept Surg, Shiraz, Iran.
   [Anbardar, Mohammad Hossein] Shiraz Univ Med Sci, Dept Pathol, Shiraz, Iran.
   [Tayebi, Lobat] Marquette Univ, Sch Dent, Milwaukee, WI 53233 USA.
   [Vafa, Ehsan; Abbasi, Milad; Amani, Ali Mohammad] Shiraz Univ Med Sci, Dept Med Nanotechnol, Sch Adv Med Sci & Technol, Shiraz, Iran.
   [Vaez, Ahmad] Shiraz Univ Med Sci, Sch Adv Med Sci & Technol, Dept Tissue Engn & Appl Cell Sci, Shiraz, Iran.
   [Golchin, Ali] Urmia Univ Med Sci, Cellular & Mol Med Inst, Solid Tumor Res Ctr, Orumiyeh, Iran.
   [Golchin, Ali] Urmia Univ Med Sci, Sch Med, Dept Clin Biochem & Appl Cell Sci, Orumiyeh, Iran.
   [Jangjou, Ali] Shiraz Univ Med Sci, Sch Med, Namazi Teaching Hosp, Dept Emergency Med, Shiraz, Iran.
C3 Shiraz University of Medical Science; Shiraz University of Medical
   Science; Shiraz University of Medical Science; Marquette University;
   Shiraz University of Medical Science; Shiraz University of Medical
   Science; Urmia University of Medical Sciences; Urmia University of
   Medical Sciences; Shiraz University of Medical Science
RP Jangjou, A (通讯作者)，Shiraz Univ Med Sci, Sch Med, Namazi Teaching Hosp, Dept Emergency Med, Shiraz, Iran.
EM ali_jangjou@ymail.com
FU National Institute of Dental & Craniofacial Research of the National
   Institutes of Health [R15DE027533, R56 DE029191, 3R15DE027533-01A1W]
FX Part of the research reported in this study was supported by the
   National Institute of Dental & Craniofacial Research of the National
   Institutes of Health under award numbers R15DE027533, R56 DE029191, and
   3R15DE027533-01A1W.
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NR 332
TC 0
Z9 0
U1 1
U2 1
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0949-2321
EI 2047-783X
J9 EUR J MED RES
JI Eur. J. Med. Res.
PD NOV 4
PY 2022
VL 27
IS 1
AR 232
DI 10.1186/s40001-022-00833-6
PG 37
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA 5Y0YP
UT WOS:000879017800002
PM 36333816
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Al-Moujahed, A
   Vail, D
   Do, DV
AF Al-Moujahed, Ahmad
   Vail, Daniel
   Do, Diana, V
TI Racial Differences in Anti-VEGF Intravitreal Injections Among
   Commercially Insured Beneficiaries
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID PROLIFERATIVE DIABETIC-RETINOPATHY; OPEN-ANGLE GLAUCOMA; EYE CARE;
   MACULAR DEGENERATION; PANRETINAL PHOTOCOAGULATION; VISUAL IMPAIRMENT;
   ASIAN-AMERICANS; UNITED-STATES; DISPARITIES; RANIBIZUMAB
AB BACKGROUND AND OBJECTIVE: This study assessed racial and ethnic differences in receiving anti-vascular endothelial growth factor (VEGF) intravitreal injections among commercially insured patients.
   PATIENTS AND METHODS: A retrospective cohort study of 104,430 patients diagnosed with wet age-related macular degeneration (AMD), diabetic retinopathy, central retinal vein occlusion (CRVO), and branch retinal vein occlusion (BRVO) in the Optum Research Database between 2011 and 2016. Main outcomes included receiving an intravitreal anti-VEGF treatment; the first type of treatment received, if any; and subsequent treatment with ranibizumab or aflibercept among patients who were first treated with bevacizumab.
   RESULTS: In a logistic regression model in all 104,430 patients, Asian patients were significantly less likely to receive an anti-VEGF treatment compared to white patients (odds ratio [OR] = 0.725; 95% confidence interval [CI], 0.667-0.789; P <.001), but Black and Hispanic patients were not. Overall, 19.9% (n = 20,753) of all included patients received treatment with intravitreal injections of anti-VEGF or steroids. In multinomial logistic models of treatment type among all patients who received intravitreal injections, Hispanic patients were less likely than white patients to initially be treated with ranibizumab (relative risk ratio [RRR] = 0.776; 95% CI, 0.647-0.929; P =.006) or aflibercept (RRR = 0.794; 95% CI, 0.654-0.964; P =.020). Black and Asian patients were not significantly more or less likely to receive different types of first-line injections compared to white patients. Among 17,092 patients who received bevacizumab as first-line therapy, Hispanic patients were less likely to subsequently transition to aflibercept than their white counterparts (RRR = 0.756; 95% CI, 0.634-0.903; P =.002).
   CONCLUSIONS: The authors found minimal racial and ethnic differences in receiving anti-VEGF treatment among commercially insured patients with wet AMD, diabetic retinopathy, CRVO, and BRVO. These results are limited by the fact that all of the patients included were commercially insured, and there are limited data on the socioeconomic status of the patients in their sample.
C1 [Al-Moujahed, Ahmad; Vail, Daniel; Do, Diana, V] Stanford Univ, Sch Med, Dept Ophthalmol, Byers Eye Inst,Horngren Family Vitreoretinal Ctr, Palo Alto, CA 94303 USA.
C3 Stanford University
RP Do, DV (通讯作者)，Stanford Univ, Sch Med, Dept Ophthalmol, Byers Eye Inst, 2370 Watson Court,Suite 228, Palo Alto, CA 94303 USA.
EM dianado@stanford.edu
CR [Anonymous], 2011, DRUG APPR PACK
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NR 57
TC 1
Z9 1
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD APR
PY 2021
VL 52
IS 4
BP 208
EP +
DI 10.3928/23258160-20210330-05
PG 17
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA RP5CB
UT WOS:000641744800005
PM 34039186
DA 2022-11-30
ER

PT J
AU Samson, FP
   Fabunmi, TE
   Patrick, AT
   Jee, D
   Gutsaeva, DR
   Jahng, WJ
AF Samson, Faith Pwaniyibo
   Fabunmi, Tosin Esther
   Patrick, Ambrose Teru
   Jee, Donghyun
   Gutsaeva, Diana R.
   Jahng, Wan Jin
TI Fatty Acid Composition and Stoichiometry Determine the Angiogenesis
   Microenvironment
SO ACS OMEGA
LA English
DT Article
AB The current study tested the hypothesis of whether specific lipids may control angiogenic reactions. Using the chorioallantoic membrane assay of the chick embryo, new vessel formation was analyzed quantitatively by gas chromatography and mass spectrometry as well as bioinformatics tools including an angiogenesis analyzer. Our biochemical experiments showed that a specific lipid composition and stoichiometry determine the angiogenesis microenvironment to accelerate or inhibit vessel formation. Specific lipids of angiogenesis determinants in the vessel area and the non-vessel area were identified as nitrooleic acid, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), palmitic acid, oleic acid, linoleic acid, linolenic acid, epoxyoleic acid, lysophosphatidylcholine (LPC), cholesterol, 7-ketocholesterol, and docosahexaenoyl lysophosphatidylcholine (DHA-LPC). Vessel formation happens on the surface area of the hydrophilic membrane of the yolk. Our biochemical data demonstrated that angiogenesis was followed in the white lipid complex area to generate more branches, junctions, segments, and extremities. We analyzed lipid fragments in the vessel, non-vessel, and albumen area to show that each area contains a specific lipid composition and stoichiometry. Mass spectrometry data demonstrated that the vessel area has higher concentrations of nitrooleic acid, palmitic acid, stearic acid, LPC, lysophosphatidylethanolamine, cholesterol, oleic acid, linoleic acid, 7-ketocholesterol, and DHA-LPC; however, DHA and EPA were abundant in the hydrophobic non-vessel area. The purpose of vessel formation is to wrap up the yolk area to transport nutrients including specific fatty acids. Besides, angiogenesis requires aqueous albumen shown by distance-dependent vessel formation from albumen and oxygen. Higher concentrations of fatty acids are required for energy and carbon structure from the carbon-carbon bond, membrane building blocks, and amphiphilic detergent to solubilize a hydrophobic environment in the aqueous blood layer. The current study may guide that the uncovered hydrophobic or zwitterionic molecules such as DHA and DHA-LPC may control angiogenesis as antiangiogenic or proangiogenic molecules as potential drug targets for treating uncontrolled angiogenesis-related diseases, including diabetic retinopathy and age-related macular degeneration.
C1 [Samson, Faith Pwaniyibo; Fabunmi, Tosin Esther; Patrick, Ambrose Teru; Jahng, Wan Jin] Amer Univ Nigeria, Dept Petr Chem, Yola 640101, Nigeria.
   [Jee, Donghyun] Catholic Univ Korea, Coll Med, Dept Ophthalmol & Visual Sci, St Vincents Hosp, Suwon 16247, South Korea.
   [Gutsaeva, Diana R.] Augusta Univ, Dept Ophthalmol, Augusta, GA 30912 USA.
C3 American University of Nigeria; Catholic University of Korea; University
   System of Georgia; Augusta University
RP Jahng, WJ (通讯作者)，Amer Univ Nigeria, Dept Petr Chem, Yola 640101, Nigeria.
EM wan.jahng@aun.edu.ng
RI Jahng, Wan Jin/C-1236-2018
OI Jahng, Wan Jin/0000-0001-8241-7739
FU American University of Nigeria; Julia Foundation
FX The current research was supported in part by the Research Assistantship
   and Teaching Assistantship from the American University of Nigeria and
   Julia Foundation. The authors are grateful to Joshua Madu, Muhammad
   Falalu Yahaya, and Emmanuel Alakunle for their excellent technical
   assistance.
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NR 58
TC 5
Z9 5
U1 1
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 2470-1343
J9 ACS OMEGA
JI ACS Omega
PD MAR 2
PY 2021
VL 6
IS 8
BP 5953
EP 5961
DI 10.1021/acsomega.1c00196
EA FEB 2021
PG 9
WC Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry
GA QT0FY
UT WOS:000626269800086
PM 33681633
OA Green Published
DA 2022-11-30
ER

PT J
AU Wang, X
   Tang, FY
   Chen, H
   Luo, LY
   Tang, ZQ
   Ran, AR
   Cheung, CY
   Heng, PA
AF Wang, Xi
   Tang, Fangyao
   Chen, Hao
   Luo, Luyang
   Tang, Ziqi
   Ran, An-Ran
   Cheung, Carol Y.
   Heng, Pheng-Ann
TI UD-MIL: Uncertainty-Driven Deep Multiple Instance Learning for OCT Image
   Classification
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Article
DE Training; Retina; Uncertainty; Informatics; Biomedical imaging;
   Supervised learning; Visualization; Optical coherence tomography;
   multiple instance learning; uncertainty estimation; classification
ID OPTICAL COHERENCE TOMOGRAPHY; DIABETIC MACULAR EDEMA; ANOMALY DETECTION;
   DEGENERATION; NETWORK
AB Deep learning has achieved remarkable success in the optical coherence tomography (OCT) image classification task with substantial labelled B-scan images available. However, obtaining such fine-grained expert annotations is usually quite difficult and expensive. How to leverage the volume-level labels to develop a robust classifier is very appealing. In this paper, we propose a weakly supervised deep learning framework with uncertainty estimation to address the macula-related disease classification problem from OCT images with the only volume-level label being available. First, a convolutional neural network (CNN) based instance-level classifier is iteratively refined by using the proposed uncertainty-driven deep multiple instance learning scheme. To our best knowledge, we are the first to incorporate the uncertainty evaluation mechanism into multiple instance learning (MIL) for training a robust instance classifier. The classifier is able to detect suspicious abnormal instances and abstract the corresponding deep embedding with high representation capability simultaneously. Second, a recurrent neural network (RNN) takes instance features from the same bag as input and generates the final bag-level prediction by considering the individually local instance information and globally aggregated bag-level representation. For more comprehensive validation, we built two large diabetic macular edema (DME) OCT datasets from different devices and imaging protocols to evaluate the efficacy of our method, which are composed of 30,151 B-scans in 1,396 volumes from 274 patients (Heidelberg-DME dataset) and 38,976 B-scans in 3,248 volumes from 490 patients (Triton-DME dataset), respectively. We compare the proposed method with the state-of-the-art approaches, and experimentally demonstrate that our method is superior to alternative methods, achieving volume-level accuracy, F1-score and area under the receiver operating characteristic curve (AUC) of 95.1%, 0.939 and 0.990 on Heidelberg-DME and those of 95.1%, 0.935 and 0.986 on Triton-DME, respectively. Furthermore, the proposed method also yields competitive results on another public age-related macular degeneration OCT dataset, indicating the high potential as an effective screening tool in the clinical practice.
C1 [Wang, Xi; Luo, Luyang; Heng, Pheng-Ann] Chinese Univ Hong Kong, Dept Comp Sci & Engn, Hong Kong, Peoples R China.
   [Tang, Fangyao; Tang, Ziqi; Ran, An-Ran; Cheung, Carol Y.] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Peoples R China.
   [Chen, Hao] Imsight Med Technol Co Ltd, Shenzhen 518108, Peoples R China.
C3 Chinese University of Hong Kong; Chinese University of Hong Kong
RP Chen, H (通讯作者)，Imsight Med Technol Co Ltd, Shenzhen 518108, Peoples R China.
EM xiwang@cse.cuhk.edu.hk; fangyaotang@cuhk.edu.hk; hchen@cse.cuhk.edu.hk;
   lyluo@cse.cuhk.edu.hk; tangdalun@link.cuhk.edu.hk;
   emma_anran@link.cuhk.edu.hk; carolcheung@cuhk.edu.hk;
   pheng@cse.cuhk.edu.hk
RI Chen, Hao/V-4299-2019
OI Chen, Hao/0000-0002-8400-3780; Heng, Pheng Ann/0000-0003-3055-5034;
   Wang, Xi/0000-0002-5218-2761; Ran, Anran/0000-0003-4592-4867; Luo,
   Luyang/0000-0002-7485-4151
FU Hong Kong Innovation and Technology Fund [ITS/311/18FP]; Research Grants
   Council -General Research Fund, Hong Kong [14102418]
FX This work was supported in part by Hong Kong Innovation and Technology
   Fund under Project ITS/311/18FP and in part by the Research Grants
   Council -General Research Fund, Hong Kong (Ref: 14102418).
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NR 58
TC 19
Z9 20
U1 4
U2 12
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2194
EI 2168-2208
J9 IEEE J BIOMED HEALTH
JI IEEE J. Biomed. Health Inform.
PD DEC
PY 2020
VL 24
IS 12
BP 3431
EP 3442
DI 10.1109/JBHI.2020.2983730
PG 12
WC Computer Science, Information Systems; Computer Science,
   Interdisciplinary Applications; Mathematical & Computational Biology;
   Medical Informatics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Mathematical & Computational Biology; Medical
   Informatics
GA PC7JM
UT WOS:000597173000010
PM 32248132
DA 2022-11-30
ER

PT J
AU Velaga, SB
   Nittala, MG
   Vupparaboina, KK
   Jana, S
   Chhablani, J
   Haines, J
   Pericak-Vance, MA
   Stambolian, D
   Sadda, SR
AF Velaga, Swetha B.
   Nittala, Muneeswar G.
   Vupparaboina, Kiran K.
   Jana, Soumya
   Chhablani, Jay
   Haines, Jonathan
   Pericak-Vance, Margaret A.
   Stambolian, Dwight
   Sadda, Srinivas R.
TI CHOROIDAL VASCULARITY INDEX AND CHOROIDAL THICKNESS IN EYES WITH
   RETICULAR PSEUDODRUSEN
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE choroidal vascularity index; choroidal thickness; choroidal volume;
   choroidal intensity; age-related macular degeneration; nonneovascular
   age-related macular degeneration; reticular pseudodrusen
ID MACULAR DEGENERATION; HEALTHY EYES; GEOGRAPHIC ATROPHY; AGE; VOLUME;
   ASSOCIATION; BINARIZATION; SECONDARY; DENSITY
AB Purpose: To evaluate choroidal vascularity index (CVI), choroidal thickness, choroidal volume, and choroidal intensity in subjects with nonneovascular age-related macular degeneration (NNVAMD) with and without reticular pseudodrusen (RPD). Methods: We included 60 eyes of 35 subjects with NNVAMD (including 30 eyes of 18 subjects with RPD) and 30 eyes of 17 age-matched healthy individuals from the ongoing Amish Eye study. The choroid was segmented from dense volume spectral domain optical coherence tomography scans and choroidal thickness (microns), choroidal intensity (log units), and choroidal volume (mm(3)) from the entire macula (6 x 6 mm) were computed. A central horizontal B-scan was binarized and the luminal and stromal portions of the choroid were segmented. Choroidal vascularity index (%) was calculated as the ratio of luminal area to total choroid area. Choroidal parameters were compared between the groups by pairwise comparisons using the Student's t-test. Results: The CVI was significantly lower in healthy eyes compared to those with RPD (53.43 +/- 8.51 vs. 54.76 +/- 4.83, P < 0.001). The CVI was also significantly lower in NNVAMD eyes without RPD compared to those with RPD (50.09 +/- 7.51 vs. 54.76 +/- 4.83, P = 0.006). There was no difference in CVI between healthy eyes and NNVAMD eyes without RPD (P = 0.84). Choroidal thickness and choroidal volume were significantly higher in NNVAMD without RPD (P < 0.05); and significantly lower in NNVAMD with RPD (P < 0.05) when compared with normal eyes. Choroidal intensity was significantly higher in NNVAMD with RPD when compared with normal eyes (P = 0.02) and NNVAMD eyes without RPD (P = 0.001). Conclusion: Multiple choroidal parameters reflecting the status of the choroidal vasculature and stroma seem to be altered in eyes with RPD compared with both normal eyes and NNVAMD eyes without RPD. These findings may provide insights into the pathophysiology of RPD.
C1 [Velaga, Swetha B.; Nittala, Muneeswar G.; Sadda, Srinivas R.] Doheny Eye Inst, 1355 San Pablo St DVRC 211, Los Angeles, CA 90033 USA.
   [Vupparaboina, Kiran K.; Jana, Soumya] Indian Inst Technol Hyderabad, Dept Elect Engn, Hyderabad, Telangana, India.
   [Chhablani, Jay] LV Prasad Eye Inst, Smt Kanuri Santhamma Retina Vitreous Ctr, Kallam Anji Reddy Campus,LV Prasad Marg, Hyderabad, India.
   [Haines, Jonathan] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
   [Haines, Jonathan] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Inst Computat Biol, Cleveland, OH 44106 USA.
   [Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Dept Genet, Miami, FL 33136 USA.
   [Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Sadda, Srinivas R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
C3 Doheny Eye Institute; Indian Institute of Technology System (IIT
   System); Indian Institute of Technology (IIT) - Hyderabad; L. V. Prasad
   Eye Institute; Case Western Reserve University; Case Western Reserve
   University; University of Miami; University of Pennsylvania;
   Pennsylvania Medicine; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA
RP Sadda, SR (通讯作者)，Doheny Eye Inst, 1355 San Pablo St DVRC 211, Los Angeles, CA 90033 USA.
EM ssadda@doheny.org
RI Jana, Soumya/AAQ-7977-2020; Nittala, Muneeswar/AAT-7533-2020
OI Chhablani, Jay/0000-0003-1772-3558
FU National Eye Institute, Bethesda, Maryland [RO1 EY023164]
FX National Eye Institute, Bethesda, Maryland Grant #RO1 EY023164.
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NR 31
TC 23
Z9 23
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD APR
PY 2020
VL 40
IS 4
BP 612
EP 617
DI 10.1097/IAE.0000000000002667
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LB2WI
UT WOS:000524497800003
PM 31634322
DA 2022-11-30
ER

PT J
AU Esmaeili, M
   Dehnavi, AM
   Hajizadeh, F
   Rabbani, H
AF Esmaeili, Mahad
   Dehnavi, Alireza Mehri
   Hajizadeh, Fedra
   Rabbani, Hosseini
TI Three-dimensional curvelet-based dictionary learning for speckle noise
   removal of optical coherence tomography
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID FUZZY ANISOTROPIC DIFFUSION; LAYER SEGMENTATION; REDUCTION; IMAGES;
   SUPPRESSION; EXTRACTION; TRANSFORM; SPARSE; FILTER
AB Optical coherence tomography (OCT) is a recently emerging non-invasive diagnostic tool useful in several medical applications such as ophthalmology, cardiology, gastroenterology and dermatology. One of the major problems with OCT pertains to its low contrast due to the presence of multiplicative speckle noise, which limits the signal-to-noise ratio (SNR) and obscures low-intensity and small features. In this paper, we recommend a new method using the 3D curvelet based K-times singular value decomposition (K-SVD) algorithm for speckle noise reduction and contrast enhancement of the infra-retinal layers of 3D Spectral-Domain OCT (3D-SDOCT) images. In order to benefit from the near-optimum properties of curvelet transform (such as good directional selectivity) on top of dictionary learning, we propose a new plan in dictionary learning by using the curvelet atoms as the initial dictionary. For this reason, the curvelet transform of the noisy image is taken and then the noisy coefficients matrix in each scale, rotation and spatial coordinates is passed through the K-SVD denoising algorithm with predefined 3D initial dictionary that is adaptively selected from thresholded coefficients in the same subband of the image. During the denoising of curvelet coefficients, we can also modify them for the purpose of contrast enhancement of infra-retinal layers. We demonstrate the ability of our proposed algorithm in the speckle noise reduction of 17 publicly available 3D OCT data sets, each of which contains 100 B-scans of size 512x1000 with and without neovascular age-related macular degeneration (AMD) images acquired using SDOCT, Bioptigen imaging systems. Experimental results show that an improvement from 1.27 to 7.81 in contrast to noise ratio (CNR), and from 38.09 to 1983.07 in equivalent number of looks (ENL) is achieved, which would outperform existing state-of-the-art OCT despeckling methods. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
C1 [Esmaeili, Mahad; Dehnavi, Alireza Mehri; Rabbani, Hosseini] Isfahan Univ Med Sci, Med Image & Signal Proc Res Ctr, Sch Adv Technol Med, Dept Bioelect & Biomed Engn, Esfahan, Iran.
   [Esmaeili, Mahad] Tabriz Univ Med Sci, Fac Adv Med Sci, Dept Med Bioengn, Tabriz, Iran.
   [Hajizadeh, Fedra] Noor Eye Hosp, Noor Ophthalmol Res Ctr, Tehran, Iran.
C3 Isfahan University Medical Science; Tabriz University of Medical Science
RP Rabbani, H (通讯作者)，Isfahan Univ Med Sci, Med Image & Signal Proc Res Ctr, Sch Adv Technol Med, Dept Bioelect & Biomed Engn, Esfahan, Iran.
EM rabbani.h@ieee.org
FU Isfahan University of Medical Sciences [195084, 196076, 393733]
FX Isfahan University of Medical Sciences (195084, 196076, 393733).
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NR 72
TC 10
Z9 10
U1 4
U2 12
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD FEB 1
PY 2020
VL 11
IS 2
BP 586
EP 608
DI 10.1364/BOE.377021
PG 23
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
GA KT5QQ
UT WOS:000519069700005
PM 32133216
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Ford, KM
   D'Amore, PA
AF Ford, Knatokie M.
   D'Amore, Patricia A.
TI Molecular regulation of vascular endothelial growth factor expression in
   the retinal pigment epithelium
SO MOLECULAR VISION
LA English
DT Article
ID TRANSCRIPTIONAL REGULATION; CELL DIFFERENTIATION; EYE DEVELOPMENT; VEGF;
   ADULT; CHORIOCAPILLARIS; ANGIOGENESIS; LOCALIZATION; ACTIVATION;
   SECRETION
AB Purpose: Vascular endothelial growth factor (VEGF) plays an important role in homeostasis and diseases of the retinal pigment epithelium (RPE), choriocapillaris, and, most notably, age-related macular degeneration (AMD). Although much is known about VEGF regulation in pathologies, little is known about the control of VEGF expression under normal conditions. VEGF expression has been previously shown to be regulated in coordination with cell differentiation in the muscle and kidney. We therefore tested the hypothesis that VEGF in the adult RPE would similarly be regulated in conjunction with differentiation.
   Methods: A human retinal pigment epithelium cell line (ARPE-19), a line of immortalized human RPE cells, was used for all experiments. RPE cells were polarized in culture for 4 weeks on laminin-coated Transwells. Levels of VEGF mRNA and protein were determined with real-time PCR and enzyme-linked immunosorbent assay, respectively. VEGF-luciferase reporter constructs were used to identify regions of the VEGF promoter that control VEGF expression in the RPE. Microphthalmia-associated transcription factor (MITF)-Tfe transcription factors were blocked using either a pan MITF-Tfe dominant negative or specific small interfering RNA (siRNA).
   Results: VEGF mRNA and protein secretion increased over time in the RPE cells cultured on Transwells, with protein secretion occurring in a polarized fashion primarily toward the basolateral side. Overexpression of a dominant negative that targets the MITF-Tfe family resulted in a 50% reduction in VEGF expression. The role of the MITF-Tfe family in VEGF regulation in the RPE was corroborated in studies with the VEGF-luciferase reporter constructs, where deletion of the distal VEGF promoter region containing putative binding sites for the MITF-Tfe family resulted in a 50% reduction in VEGF promoter activity. siRNA knockdown of the MITF-Tfe family individually, and in combination, revealed that downregulation of Tfe3 resulted in reduced VEGF expression.
   Conclusions: Our results indicate that Tfe3, in conjunction with other MITF-Tfe members, regulates VEGF expression in the RPE and are consistent with the hypothesis that VEGF expression in RPE cells is regulated as part of their differentiation.
C1 [Ford, Knatokie M.; D'Amore, Patricia A.] Schepens Eye Res Inst Massachusetts Eye & Ear, Boston, MA 02114 USA.
   [Ford, Knatokie M.; D'Amore, Patricia A.] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA.
   [D'Amore, Patricia A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
   [Ford, Knatokie M.; D'Amore, Patricia A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard
   Medical School; Harvard University; Harvard Medical School
RP D'Amore, PA (通讯作者)，Schepens Eye Res Inst Massachusetts Eye & Ear, 20 Staniford St, Boston, MA 02114 USA.
EM patricia.damore@schepens.harvard.edu
RI D'Amore, Patricia A/G-5660-2017
OI D'Amore, Patricia A/0000-0001-9652-8974
FU [R01EY015435]; NATIONAL EYE INSTITUTE [R01EY015435] Funding Source: NIH
   RePORTER
FX The authors thank Dr. Eiichi Sekiyama for providing the image of
   occludin localization in polarized ARPE-19 cells, Tomoki Kurihara for
   performing the ELISA assay of the conditioned ARPE-19 media, and Mrs.
   Christine Bagley for her editorial assistance. This work was supported
   by R01EY015435 (P.A.D.).
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NR 36
TC 28
Z9 28
U1 0
U2 4
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD MAR 1
PY 2012
VL 18
IS 57-59
BP 519
EP 527
PG 9
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 905JO
UT WOS:000301268600001
PM 22419845
DA 2022-11-30
ER

PT J
AU Guduric-Fuchs, J
   Chen, W
   Price, H
   Archer, DB
   Cogliati, T
AF Guduric-Fuchs, Jasenka
   Chen, Wing
   Price, Henrietta
   Archer, Desmond B.
   Cogliati, Tiziana
TI RPE and neuronal differentiation of allotransplantated porcine ciliary
   epithelium-derived cells
SO MOLECULAR VISION
LA English
DT Article
ID RETINAL STEM-CELLS; TRANSPLANTED PHOTORECEPTOR PRECURSORS; ADULT
   MAMMALIAN EYE; PROGENITOR CELLS; PIGMENT-EPITHELIUM; IN-VITRO;
   VERTEBRATE RETINA; SUBRETINAL SPACE; VISUAL FUNCTION; GROWTH-FACTOR
AB Purpose: Cell replacement has the potential to be applied as a therapeutic strategy in retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration (AMD) for which no adequate pharmacological and surgical treatments are currently available. Although controversial, the use of ciliary epithelium (CE)-derived cells is supported by evidence showing their differentiation into retinal phenotypes. This study examines the differentiation potential of porcine CE-derived cells in vitro and their survival, migration, morphological characteristics, and immunohistochemical phenotype in vivo, upon transplantation into the subretinal space of normal pigs.
   Methods: Cells were isolated from the CE of postnatal pigs and were grown in a suspension sphere culture. Differentiation was assessed in vitro after exposure to laminin and the addition of serum. For transplantation, CE-derived spheres were dissociated, labeled with CM-DiI vital dye, and the cells were injected subretinally into one eye of eight week-old allorecipients. The eyes were examined at eight days and at two and four weeks after transplantation.
   Results: Cells positive for neuronal and retinal pigment epithelium (RPE) markers were detected by immunohistochemistry in differentiation cultures. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) revealed upregulation of neuronal markers after in vitro differentiation. CM-DiI dye-labeled CE-derived cells dissociated from primary spheres survived for up to four weeks after transplantation in vivo. Some of the surviving cells migrated distantly from the injection site. Large clusters of transplanted cells integrated into the RPE layer and multilayered RPE-like structures positive for RPE65 were often observed. Grafted cells were also identified in the neuroretina where 5%-10% were positive for recoverin, protein kinase C alpha (PKC alpha), and calbindin.
   Conclusions: The efficient conversion to an RPE-like phenotype suggests that CE-derived cells could be a potential source of RPE for cell replacement. Our data also suggest that the ability of these cells to acquire neuronal phenotypes is influenced by the environment. Thus, pre-differentiated or (re)programmed CE-derived cells may be more amenable for retinal repair.
C1 [Guduric-Fuchs, Jasenka; Archer, Desmond B.; Cogliati, Tiziana] Queens Univ Belfast, Ctr Vis & Vasc Sci, Royal Victoria Hosp, Inst Clin Sci, Belfast BT7 1NN, Antrim, North Ireland.
   [Chen, Wing] Royal Victoria Hosp, Belfast BT12 6BA, Antrim, North Ireland.
   [Price, Henrietta] AFBI, Chem Surveillance Branch, Vet Sci Div, Belfast, Antrim, North Ireland.
C3 Queens University Belfast; Agri-Food & Biosciences Institute
RP Guduric-Fuchs, J (通讯作者)，RVH Inst Clin Sci, QUB Ctr Vis & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland.
EM j.guduricfuchs@qub.ac.uk
FU Fighting Blindness; Fraser Homes Foundation for Ophthalmic Research,
   UK.; ROI
FX The authors thank Alan Stitt for valuable comments, Taz McClintock, Paul
   Crawford, David Beattie, Lorraine Hanna and Mildred Wylie for technical
   support, Elaine Latimer for project coordination, Robert Molday and
   Karl-Wilhelm Koch for kindly donating antibodies. This work was
   supported in part by funding generously provided by Fighting Blindness,
   ROI and The Fraser Homes Foundation for Ophthalmic Research, UK.
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NR 70
TC 11
Z9 11
U1 0
U2 1
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD OCT 5
PY 2011
VL 17
IS 279-82
BP 2580
EP 2595
PG 16
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 833NJ
UT WOS:000295891900001
PM 22025893
DA 2022-11-30
ER

PT J
AU Augustin, AJ
   Offermann, I
AF Augustin, Albert J.
   Offermann, Indre
TI Combination therapy for choroidal neovascularisation
SO DRUGS & AGING
LA English
DT Article
ID COMBINED PHOTODYNAMIC THERAPY; AGE-RELATED MACULOPATHY; INTRAVITREAL
   TRIAMCINOLONE ACETONIDE; MACULAR DEGENERATION; VERTEPORFIN THERAPY;
   PATHOLOGICAL MYOPIA; BEVACIZUMAB AVASTIN; PREVALENCE; RANIBIZUMAB;
   SECONDARY
AB Choroidal neovascularisation (CNV) often leads to severe vision loss and is becoming increasingly prevalent as the aging population grows. Age-related macular degeneration (AMD) is the most common cause of CNV, but CNV also affects younger people with pathological myopia, ocular histoplasmosis syndrome, angioid streaks and idiopathic disorders. The monotherapies available worldwide to treat patients with CNV have primarily been studied in CNV due to AMD, and all have their drawbacks. Combination therapy takes advantage of the strengths of each therapy and their different mechanisms of action to achieve good treatment outcomes with few repeated treatments. For example, combination (triple) therapy with verteporfin photodynamic therapy, anti-vascular endothelial growth factor (VEGF) therapy and anti-inflammatory therapy addresses three main targets of CNV development: the CNV itself, VEGF expression (which promotes CNV growth) and inflammation (which exacerbates the disease process). Such triple therapy has been shown to result in sustained improved vision after only one treatment. Vision outcomes similar to those observed with ranibizumab, the most promising and rigorously proven anti-VEGF monotherapy, may be possible with combination therapy without the need for continued monthly intravitreal injections, which are required if sustained outcomes are to be achieved with ranibizumab. The goal of CNV therapy is improved vision outcomes after one course of treatment. Combination therapy may lead to this goal. Such treatment could also result in fewer safety issues (fewer treatments are required and the unknown effects of continued long-term treatment are avoided), lower cost to both the patient and the medical system and greater convenience for patients (fewer clinic visits). However, combination therapy is beset with several challenges: different therapies, doses, timing and treatment sequences are possible, and it is therefore difficult to conduct large, definitive clinical trials to determine which treatment regimen is safest and most effective. Large controlled studies are needed to more clearly define effective and safe combination regimens for CNV.
C1 [Augustin, Albert J.; Offermann, Indre] Klinikum Karlsruhe, Dept Ophthalmol, D-76133 Karlsruhe, Germany.
C3 Municipal Hospital Karlsruhe
RP Augustin, AJ (通讯作者)，Klinikum Karlsruhe, Dept Ophthalmol, Moltkestr 90, D-76133 Karlsruhe, Germany.
EM 106020.560@compuserve.com
OI Augustin, Prof. Dr. Albert J./0000-0003-1591-0536
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NR 85
TC 17
Z9 19
U1 0
U2 2
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 1170-229X
EI 1179-1969
J9 DRUG AGING
JI Drugs Aging
PY 2007
VL 24
IS 12
BP 979
EP 990
DI 10.2165/00002512-200724120-00002
PG 12
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 242ED
UT WOS:000251706400001
PM 18020531
DA 2022-11-30
ER

PT J
AU Lee, JR
   Jeong, KW
AF Lee, Jae Rim
   Jeong, Kwang Won
TI NMDA Receptor Antagonists Degrade Lipofuscin via Autophagy in Human
   Retinal Pigment Epithelial Cells
SO MEDICINA-LITHUANIA
LA English
DT Article
DE retinal pigment epithelial cells; drusen;
   N-retinylidene-N-retinylethanolamine (A2E); N-methyl-D-aspartate (NMDA);
   autophagy
ID MACULAR DEGENERATION; WET AMD; A2E; FLUOROPHORE; DEATH; RPE;
   ACCUMULATION; INFLAMMATION; MECHANISMS; PROTECTION
AB Background and Objectives: Age-related macular degeneration is a slow-progressing disease in which lipofuscin accumulates in the retina, causing inflammation and apoptosis of retinal pigment epithelial (RPE) cells. This study aimed to identify N-methyl-D-aspartate (NMDA) signaling as a novel mechanism for scavenging N-retinylidene-N-retinylethanolamine (A2E), a component of ocular lipofuscin, in human RPE cells. Materials and Methods: A2E degradation assays were performed in ARPE-19 cells using fluorescently labeled A2E. The autophagic activity in ARPE-19 cells was measured upon blue light (BL) exposure, after A2E treatment. Autophagy flux was determined by measuring LC3-II formation using immunoblotting and confocal microscopy. To determine whether autophagy via the NMDA receptor is involved in A2E clearance, ATG5-deficient cells were used. Results: Ro 25-6981, an NR2B-selective NMDA receptor antagonist, effectively cleared A2E. Ro 25-6981 reduced A2E accumulation in the lysosomes of ARPE-19 cells at sub-cytotoxic concentrations, while increasing the formation of LC3-II and decreasing p62 protein levels in a concentration-dependent manner. The autophagic flux monitored by RFP-GFP-LC3 and bafilomycin A1 assays was significantly increased by Ro 25-6981. A2E clearance by Ro 25-6981 was abolished in ATG5-depleted ARPE-19 cells, suggesting that A2E degradation by Ro 25-6981 was mediated by autophagy. Furthermore, treatment with other NMDA receptor antagonists, CP-101,606 and AZD6765, showed similar effects on autophagy activation and A2E degradation in ARPE-19 cells. In contrast, glutamate, an NMDA receptor agonist, exhibited a contrasting effect, suggesting that both the activation of autophagy and the degradation of A2E by Ro 25-6981 in ARPE-19 cells occur through inhibition of the NMDA receptor pathway. Conclusions: This study demonstrates that NMDA receptor antagonists degrade lipofuscin via autophagy in human RPE cells and suggests that NMDA receptor antagonists could be promising new therapeutics for retinal degenerative diseases.
C1 [Lee, Jae Rim; Jeong, Kwang Won] Gachon Univ, Coll Pharm, Gachon Res Inst Pharmaceut Sci, 191 Hambakmoero, Incheon 21936, South Korea.
C3 Gachon University
RP Jeong, KW (通讯作者)，Gachon Univ, Coll Pharm, Gachon Res Inst Pharmaceut Sci, 191 Hambakmoero, Incheon 21936, South Korea.
EM kwjeong@gachon.ac.kr
FU National Research Foundation of Korea (NRF) - Ministry of Education
   [NRF-2021R1A2C1011132]; Gachon University Research Fund of 2020
   [GCU-202008420011]
FX This research was supported by the Basic Science Research Program of the
   National Research Foundation of Korea (NRF) funded by the Ministry of
   Education (NRF-2021R1A2C1011132) and the Gachon University Research Fund
   of 2020 (GCU-202008420011) provided to K.W.J.
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NR 58
TC 0
Z9 0
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1010-660X
EI 1648-9144
J9 MEDICINA-LITHUANIA
JI Med. Lith.
PD AUG
PY 2022
VL 58
IS 8
AR 1129
DI 10.3390/medicina58081129
PG 11
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 4B0OE
UT WOS:000845487700001
PM 36013596
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Mettu, PS
   Allingham, MJ
   Cousins, SW
AF Mettu, Priyatham S.
   Allingham, Michael J.
   Cousins, Scott W.
TI Incomplete response to Anti-VEGF therapy in neovascular AMD: Exploring
   disease mechanisms and therapeutic opportunities
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Neovascular age-related macular degeneration; Choroidal
   neovascularization; Anti-VEGF; Anti-VEGF resistance; Persistent disease
   activity; Suboptimal vision recovery; Macrophage; Monocyte; Mesenchymal
   precursor cell; Neovascular remodeling; Photoreceptor synaptic
   dysfunction; Miller cell
ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL DETACHMENT; INDOCYANINE
   GREEN ANGIOGRAPHY; TISSUE-PLASMINOGEN ACTIVATOR; VERTEPORFIN
   PHOTODYNAMIC THERAPY; POLYPOIDAL CHOROIDAL VASCULOPATHY; COHERENCE
   TOMOGRAPHY ANGIOGRAPHY; MACULAR DEGENERATION PATIENTS; THICK SUBMACULAR
   HEMORRHAGE; MITOCHONDRIA-TARGETED DRUG
AB Intravitreal anti-vascular endothelial growth factor (VEGF) drugs have revolutionized the treatment of neovascular age-related macular degeneration (NVAMD). However, many patients suffer from incomplete response to anti-VEGF therapy (IRT), which is defined as (1) persistent (plasma) fluid exudation; (2) unresolved or new hemorrhage; (3) progressive lesion fibrosis; and/or (4) suboptimal vision recovery. The first three of these collectively comprise the problem of persistent disease activity (PDA) in spite of anti-VEGF therapy. Meanwhile, the problem of suboptimal vision recovery (SVR) is defined as a failure to achieve excellent functional visual acuity of 20/40 or better in spite of sufficient anti-VEGF treatment. Thus, incomplete response to anti-VEGF therapy, and specifically PDA and SVR, represent significant clinical unmet needs.
   In this review, we will explore PDA and SVR in NVAMD, characterizing the clinical manifestations and exploring the pathobiology of each. We will demonstrate that PDA occurs most frequently in NVAMD patients who develop high-flow CNV lesions with arteriolarization, in contrast to patients with capillary CNV who are highly responsive to anti-VEGF therapy. We will review investigations of experimental CNV and demonstrate that both types of CNV can be modeled in mice. We will present and consider a provocative hypothesis: formation of arteriolar CNV occurs via a distinct pathobiology, termed neovascular remodeling (NVR), wherein blood-derived macrophages infiltrate the incipient CNV lesion, recruit bone marrow-derived mesenchymal precursor cells (MPCs) from the circulation, and activate MPCs to become vascular smooth muscle cells (VSMCs) and myofibroblasts, driving the development of high-flow CNV with arteriolarization and perivascular fibrosis. In considering SVR, we will discuss the concept that limited or poor vision in spite of anti-VEGF may not be caused simply by photoreceptor degeneration but instead may be associated with photoreceptor synaptic dysfunction in the neurosensory retina overlying CNV, triggered by infiltrating blood-derived macrophages and mediated by Miller cell activation Finally, for each of PDA and SVR, we will discuss current approaches to disease management and treatment and consider novel avenues for potential future therapies.
C1 [Mettu, Priyatham S.; Allingham, Michael J.; Cousins, Scott W.] Duke Univ, Sch Med, Dept Ophthalmol, Duke Ctr Macular Dis, Durham, NC USA.
   [Cousins, Scott W.] Duke Univ, Sch Med, Dept Immunol, Durham, NC USA.
C3 Duke University; Duke University
RP Mettu, PS (通讯作者)，Box 3802,2351 Erwin Rd, Durham, NC 27710 USA.
EM prithu.mettu@duke.edu
FU National Institutes of Health (NIH) [R01 EY018880]; NIH [R01 EY013318,
   R03 EY015292, K08 EY025325, K08 EY026627, P30 EY005722]; Research to
   Prevent Blindness Grant; Stealth BioTherapeutics; Bausch + Lomb
FX This was work was supported by National Institutes of Health (NIH) R01
   EY018880 (SWC) , NIH R01 EY013318 (SWC) , NIH R03 EY015292 (SWC) , NIH
   K08 EY025325 (PSM) , NIH K08 EY026627 (MJA) , NIH Core Grant P30
   EY005722 (to Duke Eye Center) , Unrestricted Grant from Research to
   Prevent Blindness Grant (to Duke Eye Center) , Grant funding from
   Stealth BioTherapeutics (PSM, MJA, SWC) , and Grant funding from Bausch
   + Lomb (PSM, SWC) . The funding sources/sponsors had no role in the
   design and conduct of studies, data analysis, writing, or decision to
   publish the work presented herein.
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NR 403
TC 46
Z9 48
U1 12
U2 24
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD MAY
PY 2021
VL 82
AR 100906
DI 10.1016/j.preteyeres.2020.100906
EA JUN 2021
PG 46
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA SR7TO
UT WOS:000661249300001
PM 33022379
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Sodhi, SK
   Trimboli, C
   Kalaichandran, S
   Pereira, A
   Choudhry, N
AF Sodhi, Simrat K.
   Trimboli, Carmelina
   Kalaichandran, Sivaruben
   Pereira, Austin
   Choudhry, Netan
TI A proof of concept study to evaluate the treatment response of
   aflibercept in wARMD using OCT-A (Canada study)
SO INTERNATIONAL OPHTHALMOLOGY
LA English
DT Article
DE Wet age-related macular degeneration; Optical coherence tomography
   angiography; Aflibercept; Choroidal neovascular membrane; Segmentation
AB Purpose To Utilize OCT-A to measure the change in size (mm(2)) and density (flow index) of choroidal neovascular membranes (CNVMs) from baseline to week 52 of treatment-naive wet age-related macular degeneration (wARMD) patients receiving intravitreal aflibercept injections (IAI). Methods Patients were treated with IAI at baseline, month 1 and month 2 and then every other month for a total of 12 months. Along with clinical examination and best corrected visual acuity (BCVA), OCT-A 6- and 3-mm scans were acquired at every visit between May 2017 and January 2019. Data from baseline, week 12 and week 52 were analyzed prospectively and included in the final analysis. Results Twenty-five eyes from 23 patients were included in the study. The mean BCVA at baseline and week 52 increased from 20/125 to 20/80, respectively (p < 0.001). The mean CST at baseline and week 52 decreased from 330.48 to 222.40 mu m, respectively (p < 0.001). 1Seventeen patients (18 eyes) completed all protocol-based 6 x 6 mm and 3 x 3 mm OCT-A scans. In this subgroup, 6-mm OCT-A scans revealed that the mean size of the CNVM before and after IAI was 1.21 mm(2) and 0.56 mm(2), respectively (p < 0.001), while the 3-mm OCT-A scans at baseline and week 52 demonstrated a decrease in mean size of the CNVM from 0.89 to 0.37 mm(2), respectively (p < 0.001). The 6-mm perfusion density map revealed no difference at either time points. Conclusions OCT-A provides a useful approach for monitoring and evaluating the treatment of intravitreal aflibercept for CNVMs. Mean size of CNVMs can be identified by 3- or 6-mm scans, but without machine learning, it requires extensive segmentation. While reproducibility and clear delineation of CNVMs in wARMD using OCT-A is challenging, OCT-A does offer the ability to monitor CNVM size changes during treatment and may offer another biomarker to assist in assessing treatment response.
C1 [Sodhi, Simrat K.] Univ Cambridge, Cambridge, England.
   [Trimboli, Carmelina; Choudhry, Netan] Vitreous Retina Macula Specialists Toronto, 3280 Bloor St West,Suite 310, Etobicoke, ON M8X 2X3, Canada.
   [Kalaichandran, Sivaruben] Univ Toronto, Fac Med, Toronto, ON, Canada.
   [Pereira, Austin; Choudhry, Netan] Univ Toronto, Dept Ophthalmol & Visual Sci, Toronto, ON, Canada.
C3 University of Cambridge; University of Toronto; University of Toronto
RP Choudhry, N (通讯作者)，Vitreous Retina Macula Specialists Toronto, 3280 Bloor St West,Suite 310, Etobicoke, ON M8X 2X3, Canada.
EM netan.choudhry@vrmto.com
FU Bayer Inc.
FX This study was supported by funding from Bayer Inc.
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NR 48
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0165-5701
EI 1573-2630
J9 INT OPHTHALMOL
JI Int. Ophthalmol.
PD MAY
PY 2021
VL 41
IS 5
BP 1697
EP 1708
DI 10.1007/s10792-021-01726-z
EA FEB 2021
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RV6IQ
UT WOS:000615773000001
PM 33550508
DA 2022-11-30
ER

PT J
AU Lamin, A
   El Nokrashy, A
   Chandra, S
   Sivaprasad, S
AF Lamin, Ali
   ElNokrashy, Amgad
   Chandra, Shruti
   Sivaprasad, Sobha
TI Association of Longitudinal Changes in Drusen Characteristics and
   Retinal Layer Volumes with Subsequent Subtype of Choroidal
   Neovascularisation
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Choroidal neovascularisation type;
   Drusen load; Retinal layer volumes; Imaging biomarkers
ID MACULAR DEGENERATION; FELLOW EYES; RANIBIZUMAB; VERTEPORFIN
AB Aim: To investigate the longitudinal correlation between drusen characteristics and retinal layer volumes pre conversion and subsequent type of choroidal neovascularisation (CNV). Methods: This was a single-centre retrospective study. The study participants were patients with wet age-related macular degeneration (AMD) in one eye who developed wet AMD in the contralateral eye, with at least 2 years of follow-up prior to conversion. The Moorfields Eye Hospital database was searched for eligible patients and their data were recorded. Eyes were classified as occult or classic based on fundus fluorescein angiography. Optical coherence tomography (OCT) images were analysed for drusen characteristics and retinal layer volumes were analysed over time using automated software (Topcon 3D OCT-2000 and Orion, Voxeleron LLC, respectively). All values were obtained at baseline as well as year 1 and year 2 before conversion to wet AMD. Results: Fifty-one eyes with bilateral CNV showed high correlation of type of CNV between eyes (kappa statistic 0.89). A total of 49 wet AMD eyes (29 occult, 20 classic) were analysed for drusen parameters. Two patients with retinal angiomatous proliferation were excluded. Drusen count, area, and volume did not differ by CNV type, but the rates of change of drusen area (p = 0.046) and drusen volume (0.022) were higher in the occult group in the year preceding CNV development. Of the 49 eyes, 17 (10 occult, 7 classic) with available good quality OCT were analysed for retinal layer volumes. There was a progressive reduction in outer nuclear layer (ONL) volume (p = 0.002) and an expansion in outer plexiform layer volume (p = 0.015) in eyes that developed occult CNV. Conclusion: Our study shows that rate of increase in drusen load and reduction in ONL are significant features seen in eyes developing occult CNV, highlighting new imaging markers that need to be replicated in larger studies. These markers provide insight into the pathogenesis of CNV and may serve as prognostic indicators, as classic CNV carries a poorer prognosis compared to occult CNV.
C1 [Lamin, Ali; Chandra, Shruti; Sivaprasad, Sobha] Moorfields Eye Hosp NHS Fdn Trust, NIHR Moorfields Biomed Res Ctr, 162 City Rd, London EC1V 2PD, England.
   [Lamin, Ali; Chandra, Shruti; Sivaprasad, Sobha] UCL Inst Ophthalmol, London, England.
   [ElNokrashy, Amgad] Mansoura Univ, Mansoura Ophthalm Ctr, Mansoura, Egypt.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London;
   Egyptian Knowledge Bank (EKB); General Organization of Teaching
   Hospitals & Institutes (GOTHI); Research Institute of Ophthalmology
   (RIO); Mansoura University
RP Sivaprasad, S (通讯作者)，Moorfields Eye Hosp NHS Fdn Trust, NIHR Moorfields Biomed Res Ctr, 162 City Rd, London EC1V 2PD, England.
EM sobha.sivaprasad@nhs.net
OI Ali, Amgad/0000-0001-6604-7133; Sivaprasad, Sobha/0000-0001-8952-0659
FU National Institute for Health Research (NIHR) Biomedical Research Centre
   based at Moorfields Eye Hospital NHS Foundation Trust; UCL Institute of
   Ophthalmology
FX The research was supported by the National Institute for Health Research
   (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS
   Foundation Trust and UCL Institute of Ophthalmology. The views expressed
   are those of the authors and not necessarily those of the NHS, the NIHR,
   or the Department of Health.
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NR 29
TC 4
Z9 4
U1 0
U2 1
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PD JUL
PY 2020
VL 63
IS 4
BP 375
EP 382
DI 10.1159/000505628
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PI3LW
UT WOS:000600997000002
PM 31884497
OA Bronze
DA 2022-11-30
ER

PT J
AU Tian, HB
   Xu, JY
   Tian, Y
   Cao, YQ
   Lian, CP
   Ou, QJ
   Wu, BX
   Jin, CX
   Gao, FR
   Wang, J
   Zhang, JP
   Zhang, JF
   Li, WY
   Lu, LX
   Xu, GT
AF Tian, Haibin
   Xu, Jing-Ying
   Tian, Yu
   Cao, Yaqi
   Lian, Chunpin
   Ou, Qingjian
   Wu, Binxin
   Jin, Caixia
   Gao, Furong
   Wang, Juan
   Zhang, Jieping
   Zhang, Jingfa
   Li, Weiye
   Lu, Lixia
   Xu, Guo-Tong
TI A cell culture condition that induces the mesenchymal-epithelial
   transition of dedifferentiated porcine retinal pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE RPE; Age-related macular degeneration; Epithelial-mesenchymal
   transition; Mesenchymal-epithelial transition; TAZ; ZEB1
ID STEM-CELLS; TARGETING ZEB1; HIPPO PATHWAY; GROWTH-FACTOR; LUNG-CANCER;
   PROLIFERATION; EXPRESSION; STRESS; ACTIN; YAP
AB The pathological change of retinal pigment epithelial (RPE) cells is one of the main reasons for the development of age-related macular degeneration (AMD). Thus, cultured RPE cells are a proper cell model for studying the etiology of AMD in vitro. However, such cultured RPE cells easily undergo epithelial-mesenchymal transition (EMT) that results in changes of cellular morphology and functions of the cells. To restore and maintain the mesenchymal-epithelial transition (MET) of the cultured RPE cells, we cultivated dedifferentiated porcine RPE (pRPE) cells and compared their behaviors in four conditions: 1) in cell culture dishes with DMEM/F12 containing FBS (CC dish-FBS), 2) in petri dishes with DMEM/F12 containing FBS (Petri dish-FBS), 3) in cell culture dishes with DMEM/F12 containing N2 and B27 supplements (CC dish-N2B27), and 4) in petri dishes with DMEM/F12 containing N2 and B27 (Petri dish-N2B27). In addition to observing the cell morphology and behavior, RPE specific markers, as well as EMT-related genes and proteins, were examined by immunostaining, quantitative real-time PCR and Western blotting. The results showed that dedifferentiated pRPE cells maintained EMT in CC dish-FBS, Petri dish-FBS and CC dish-N2B27 groups, whereas MET was induced when the dedifferentiated pRPE cells were cultured in Petri dish-N2B27. Such induced pRPE cells showed polygonal morphology with increased expression of RPE-specific markers and decreased EMT-associated markers. Similar results were observed in induced pluripotent stem cell-derived RPE cells. Furthermore, during the re-differentiation of those dedifferentiated pRPE cells, Petri dish-N2B27 reduced the activity of RhoA and induced F-actin rearrangement, which promoted the nuclear exclusion of transcriptional co-activator with PDZ-binding motif (TAZ) and TAZ target molecule zinc finger E-box binding protein (ZEB1), both of which are EMT inducing factors. This study provides a simple and reliable method to reverse dedifferentiated phenotype of pRPE cells into epithelialized phenotype, which is more appropriate for studying AMD in vitro, and suggests that MET of other cell types might be induced by a similar approach.
C1 [Tian, Haibin; Xu, Jing-Ying; Tian, Yu; Cao, Yaqi; Lian, Chunpin; Ou, Qingjian; Wu, Binxin; Jin, Caixia; Gao, Furong; Wang, Juan; Zhang, Jieping; Zhang, Jingfa; Li, Weiye; Lu, Lixia; Xu, Guo-Tong] TUSM, Tongji Eye Inst, Shanghai Hosp 10, Dept Ophthalmol, Shanghai, Peoples R China.
   [Tian, Haibin; Xu, Jing-Ying; Tian, Yu; Cao, Yaqi; Lian, Chunpin; Ou, Qingjian; Wu, Binxin; Jin, Caixia; Gao, Furong; Wang, Juan; Zhang, Jieping; Zhang, Jingfa; Lu, Lixia; Xu, Guo-Tong] TUSM, Dept Regenerat Med, Lab Clin Visual Sci, Shanghai, Peoples R China.
   [Tian, Haibin; Xu, Jing-Ying; Tian, Yu; Cao, Yaqi; Lian, Chunpin; Ou, Qingjian; Wu, Binxin; Jin, Caixia; Gao, Furong; Wang, Juan; Zhang, Jieping; Zhang, Jingfa; Lu, Lixia; Xu, Guo-Tong] TUSM, Stem Cell Res Ctr, Shanghai, Peoples R China.
   [Zhang, Jingfa; Xu, Guo-Tong] TUSM, Dept Physiol & Pharmacol, Shanghai, Peoples R China.
   [Li, Weiye] Drexel Univ, Coll Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Tian, Haibin; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Shanghai East Hosp, Sch Med, Translat Med Ctr Stem Cell Therapy, Shanghai, Peoples R China.
   [Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China.
C3 Drexel University; Tongji University; Tongji University
RP Li, WY; Lu, LX (通讯作者)，TUSM, Tongji Eye Inst, Shanghai Hosp 10, Dept Ophthalmol, Shanghai, Peoples R China.; Xu, GT (通讯作者)，Tongji Univ, Shanghai Hosp 10, Tongji Eye Inst, Sch Med,Dept Ophthalmol, 301 Middle Yanchang Rd, Shanghai 200072, Peoples R China.
EM Weiye.Li@DrexelMed.edu; lulixia@tongji.edu.cn; gtxu@tongji.edu.cn
RI Ou, Qingjian/GON-9963-2022
OI Wu, Binxin/0000-0001-9936-9606; Ou, Qingjian/0000-0002-6881-8680
FU Ministry of Science and Technology of China [2015CB964601,
   2016YFA0101302, 2017YFA0104100]; National Natural Science Foundation
   [81770942, 81670867, 81370999, 31201084]; Shanghai Municipal Commission
   of Health and Family Planning project [201640229]; Shanghai Science and
   Technology Committee [17ZR1431300]; Shanghai East Hospital
   [ZJ2014-ZD-002]
FX This work was supported by grants obtained from the Ministry of Science
   and Technology of China (2015CB964601, 2016YFA0101302, 2017YFA0104100),
   National Natural Science Foundation (81770942, 81670867, 81370999,
   31201084) and Shanghai Municipal Commission of Health and Family
   Planning project (201640229), Shanghai Science and Technology Committee
   Grant (17ZR1431300) and the grant from Shanghai East Hospital
   ZJ2014-ZD-002.
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NR 54
TC 10
Z9 11
U1 0
U2 21
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD DEC
PY 2018
VL 177
BP 160
EP 172
DI 10.1016/j.exer.2018.08.005
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HE7OO
UT WOS:000453628000019
PM 30096326
DA 2022-11-30
ER

PT J
AU Li, ZX
   He, YF
   Keel, S
   Meng, W
   Chang, RT
   He, MG
AF Li, Zhixi
   He, Yifan
   Keel, Stuart
   Meng, Wei
   Chang, Robert T.
   He, Mingguang
TI Efficacy of a Deep Learning System for Detecting Glaucomatous Optic
   Neuropathy Based on Color Fundus Photographs
SO OPHTHALMOLOGY
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; GLOBAL PREVALENCE; POPULATION; IMPAIRMENT;
   STRATEGIES; BLINDNESS; FEATURES; CHINESE; BURDEN; COSTS
AB Purpose: To assess the performance of a deep learning algorithm for detecting referable glaucomatous optic neuropathy (GON) based on color fundus photographs.
   Design: A deep learning system for the classification of GON was developed for automated classification of GON on color fundus photographs.
   Participants: We retrospectively included 48 116 fundus photographs for the development and validation of a deep learning algorithm.
   Methods: This study recruited 21 trained ophthalmologists to classify the photographs. Referable GON was defined as vertical cup-to-disc ratio of 0.7 or more and other typical changes of GON. The reference standard was made until 3 graders achieved agreement. A separate validation dataset of 8000 fully gradable fundus photographs was used to assess the performance of this algorithm.
   Main Outcome Measures: The area under receiver operator characteristic curve (AUC) with sensitivity and specificity was applied to evaluate the efficacy of the deep learning algorithm detecting referable GON.
   Results: In the validation dataset, this deep learning system achieved an AUC of 0.986 with sensitivity of 95.6% and specificity of 92.0%. The most common reasons for false-negative grading (n = 87) were GON with coexisting eye conditions (n = 44 [50.6%]), including pathologic or high myopia (n = 37 [42.6%]), diabetic retinopathy (n = 4 [4.6%]), and age-related macular degeneration (n = 3 [3.4%]). The leading reason for false-positive results (n = 480) was having other eye conditions (n = 458 [95.4%]), mainly including physiologic cupping (n = 267 [55.6%]). Misclassification as false-positive results amidst a normal-appearing fundus occurred in only 22 eyes (4.6%).
   Conclusions: A deep learning system can detect referable GON with high sensitivity and specificity. Coexistence of high or pathologicmyopia is the most commoncause resulting in false-negative results. Physiologic cupping and pathologic myopia were the most common reasons for false-positive results. (C) 2018 by the American Academy of Ophthalmology
C1 [Li, Zhixi; He, Mingguang] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
   [He, Yifan; Meng, Wei] Guangzhou Healgoo Interact Med Technol Co Ltd, Guangzhou, Guangdong, Peoples R China.
   [Keel, Stuart; He, Mingguang] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Keel, Stuart; He, Mingguang] Univ Melbourne, Dept Ophthalmol, Melbourne, Vic, Australia.
   [Keel, Stuart; He, Mingguang] Univ Melbourne, Dept Surg, Melbourne, Vic, Australia.
   [Chang, Robert T.] Stanford Univ, Dept Ophthalmol, Byers Eye Inst, Palo Alto, CA 94304 USA.
C3 Sun Yat Sen University; Centre for Eye Research Australia; University of
   Melbourne; University of Melbourne; University of Melbourne; Stanford
   University
RP He, MG (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
EM mingguang.he@unimelb.edu.au
RI He, Mingguang/AAY-5239-2020
OI He, Mingguang/0000-0002-6912-2810; Liu, Yizhi/0000-0003-4108-9593
FU Fundamental Research Funds of the State Key Laboratory in Ophthalmology,
   National Natural Science Foundation of China [81420108008]; Science and
   Technology Planning Project of Guangdong Province [2013B20400003];
   University of Melbourne at Research Accelerator Program of Australia;
   CERA Foundation of Australia; Victorian State Government of Australia
   (Operational Infrastructure Support to the Centre for Eye Research
   Australia); Research to Prevent Blindness, Inc., New York
FX Supported in part by the Fundamental Research Funds of the State Key
   Laboratory in Ophthalmology, National Natural Science Foundation of
   China (grant no.: 81420108008); the Science and Technology Planning
   Project of Guangdong Province (grant no.: 2013B20400003); the University
   of Melbourne at Research Accelerator Program of Australia (M.H.); the
   CERA Foundation of Australia (M.H.); Victorian State Government of
   Australia (Operational Infrastructure Support to the Centre for Eye
   Research Australia); and Research to Prevent Blindness, Inc., New York
   (to Stanford University Eye Department). The sponsors or funding
   organizations had no role in the design or conduct of this research.
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NR 40
TC 313
Z9 329
U1 9
U2 68
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD AUG
PY 2018
VL 125
IS 8
BP 1199
EP 1206
DI 10.1016/j.ophtha.2018.01.023
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GN8YJ
UT WOS:000439463900018
PM 29506863
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Csincsik, L
   MacGillivray, TJ
   Flynn, E
   Pellegrini, E
   Papanastasiou, G
   Barzegar-Befroei, N
   Csutak, A
   Bird, AC
   Ritchie, CW
   Peto, T
   Lengyel, I
AF Csincsik, Lajos
   MacGillivray, Thomas J.
   Flynn, Erin
   Pellegrini, Enrico
   Papanastasiou, Giorgos
   Barzegar-Befroei, Neda
   Csutak, Adrienne
   Bird, Alan C.
   Ritchie, Craig W.
   Peto, Tunde
   Lengyel, Imre
TI Peripheral Retinal Imaging Biomarkers for Alzheimer's Disease: A Pilot
   Study
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Alzheimer's disease; Age-related macular degeneration; Drusen; Vascular
   biomarker; Image grading; Imaging; Peripheral retina; Fractal dimension;
   Tortuosity
ID AGE-RELATED MACULOPATHY; GANGLION-CELL LOSS; MACULAR DEGENERATION;
   APOLIPOPROTEIN-E; LESIONS; RISK; PATHOLOGY; VOLUME
AB Purpose: To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer's disease (AD) and its progression. Methods: Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL. Images were graded for the prevalence of age-related macular degeneration-like pathologies and retinal vascular parameters. Comparison between AD patients and controls was made using the Student t test and the chi(2) test. Results: Analysis at BL revealed a significantly higher prevalence of a hard drusen phenotype in the periphery of AD patients (14/55; 25.4%) compared to controls (2/48; 4.2%) [chi(2) = 9.9, df = 4, p = 0.04]. A markedly increased drusen number was observed at the 2-year FU in patients with AD compared to controls. There was a significant increase in venular width gradient at BL (zone C: 8.425 x 10(-3) +/- 2.865 x 10(-3) vs. 6.375 x 10(-3) +/- 1.532 x 10(-3), p = 0.008; entire image: 8.235 x 10(-3) +/- 2.839 x 10(-3) vs. 6.050 x 10(-3) +/- 1.414 x 10-(3), p = 0.004) and a significant decrease in arterial fractal dimension in AD at BL (entire image: 1.250 +/- 0.086 vs. 1.304 +/- 0.089, p = 0.049) with a trend for both at FU. Conclusions: UWF retinal imaging revealed a significant association between AD and peripheral hard drusen formation and changes to the vasculature beyond the posterior pole, at BL and after clinical progression over 2 years, suggesting that monitoring pathological changes in the peripheral retina might become a valuable tool in AD monitoring. (C) 2018 S. Karger AG, Basel
C1 [Csincsik, Lajos; Flynn, Erin; Peto, Tunde; Lengyel, Imre] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland.
   [Csincsik, Lajos; Barzegar-Befroei, Neda; Csutak, Adrienne; Bird, Alan C.; Lengyel, Imre] UCL Inst Ophthalmol, London, England.
   [MacGillivray, Thomas J.; Pellegrini, Enrico] Univ Edinburgh, Ctr Clin Brain Sci, VAMPIRE Project, Edinburgh, Midlothian, Scotland.
   [MacGillivray, Thomas J.; Papanastasiou, Giorgos] Univ Edinburgh, Edinburgh Imaging, Edinburgh, Midlothian, Scotland.
   [Flynn, Erin] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA.
   [Pellegrini, Enrico] OPTOS Plc, Dunfermline, Fife, Scotland.
   [Csutak, Adrienne] Univ Debrecen, Fac Med, Dept Ophthalmol, Debrecen, Hungary.
   [Ritchie, Craig W.] Univ Edinburgh, Ctr Dementia Prevent, Edinburgh, Midlothian, Scotland.
   [Peto, Tunde] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England.
   [Peto, Tunde] UCL, London, England.
C3 Queens University Belfast; University of London; University College
   London; University of Edinburgh; University of Edinburgh; George
   Washington University; University of Debrecen; University of Edinburgh;
   University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London
RP Lengyel, I (通讯作者)，Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Med Expt, Wellcome Wolfson Bldg,97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
EM i.lengyel@qub.ac.uk
RI Lengyel, Imre/B-5217-2009; Papanastasiou, Giorgos/ABH-8943-2020;
   Csincsik, Lajos/AAA-5744-2022
OI Lengyel, Imre/0000-0001-7467-2174; Csincsik, Lajos/0000-0001-5243-7536;
   Papanastasiou, Giorgos/0000-0002-1939-296X; MacGillivray,
   Tom/0000-0001-5120-0086; Pellegrini, Enrico/0000-0001-6913-1760
FU Bill Brown Charitable Trust Senior Research Fellowship; Moorfields Eye
   Hospital Special Trustees; Mercer Fund from Fight for Sight; Optos Plc
FX The authors would like to thank P. Ndhlovu, D. Wilson, A. Holborow, B.
   Goud, N. Cheesman, and B. Corridan for their invaluable help with the
   study, and Gavin Robertson for generating Figure 1. The research was
   supported by the Bill Brown Charitable Trust Senior Research Fellowship,
   Moorfields Eye Hospital Special Trustees, and the Mercer Fund from Fight
   for Sight (I.L). Lajos Csincsik is supported by an unrestricted PhD
   studentship from Optos Plc.
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NR 49
TC 40
Z9 42
U1 0
U2 6
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2018
VL 59
IS 4
BP 182
EP 192
DI 10.1159/000487053
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GG5OD
UT WOS:000432744600002
PM 29621759
OA Green Published, Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Natesan, S
   Krishnaswami, V
   Ponnusamy, C
   Madiyalakan, M
   Woo, T
   Palanisamy, R
AF Natesan, Subramanian
   Krishnaswami, Venkateshwaran
   Ponnusamy, Chandrasekar
   Madiyalakan, Madi
   Woo, Thomas
   Palanisamy, Rajaguru
TI Hypocrellin B and nano silver loaded polymeric nanoparticles: Enhanced
   generation of singlet oxygen for improved photodynamic therapy
SO MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
LA English
DT Article
DE Hypocrellin B; Photodynamic therapy; Singlet oxygen; Silver
   nanoparticles
ID IN-VITRO; MACULAR DEGENERATION; DELIVERY; COPOLYMER; NANOTECHNOLOGY;
   TRANSFERRIN; DRUGS
AB A nanoparticulate photodynamic approach was employed with an objective to achieve enhanced production of singlet oxygen (O-1(2)), for the management of posterior segment eye diseases like age related macular degeneration. The hypocrellin B (FIB) loaded poly lactide-co-glycolide nanoparticle formulations were incorporated with nano silver (HBS-NPs). The optimized HBS-NPs contained 2.60 +/- 0.06 mg/mL of FIB and showed (i) 135.6 to 8282 nm size range, and (ii) negative zeta potential with a narrow polydispersity index. The DSC thermograms suggested the amorphous nature of FIB inside the HBS-NPs. With the average encapsulation efficiency of 92.9 +/- 1.79%, the drug release from the HBS-NPs followed a biphasic pattern with an initial burst of 3.50% during first 8 h followed by a sustained release of 47.82% within 3 days. The interaction between nano silver and 11B as assessed by the increase in spectral intensity of Raman spectrum demonstrates that HB may be attached over the nano silver. Generation of reactive oxygen species (ROS) by HBS-NPs was significantly higher than that of HB/HB-NPs. The singlet oxygen generating efficiency assessed using EPR spectrometer follows the order of nano silver > HB-NPs > pure FIB drug solution > HBS-NPs. The HBS-NPs had a concentration and time dependent phototoxicity on A549 (human adeno lung carcinoma) cells in the presence of light providing a superior phototoxic effect (82.2% at 50 mu M) at 2 h irradiation. The CAM treated with HBS-NPs showed a significant anti-angiogenic effect compared to a blank formulation. In vivo biodistribution studies revealed that intravenous administration of HBS-NPs lead into significant exposure to the posterior segment of the eye. This proof of principle study demonstrates that HB based nanoparticles may be a valuable new tool for application in ocular photodynamic therapy for the treatment of AMD in future. (C) 2017 Elsevier B.V. All rights reserved.
C1 [Natesan, Subramanian; Krishnaswami, Venkateshwaran; Ponnusamy, Chandrasekar] Anna Univ, Bharathidasan Inst Technol, Dept Pharmaceut Technol, Lab Lipid Based Syst, Tiruchirappalli 620024, Tamil Nadu, India.
   [Palanisamy, Rajaguru] Anna Univ, Bharathidasan Inst Technol, Dept Biotechnol, Tiruchirappalli, Tamil Nadu, India.
   [Madiyalakan, Madi; Woo, Thomas] Quest Pharma Tech Inc, Edmonton, AB, Canada.
C3 Anna University; Anna University of Technology Tiruchirappalli; Anna
   University; Anna University of Technology Tiruchirappalli
RP Natesan, S (通讯作者)，Anna Univ, Bharathidasan Inst Technol, Dept Pharmaceut Technol, Lab Lipid Based Syst, Tiruchirappalli 620024, Tamil Nadu, India.
EM subramanian.n@aubit.edu.in
RI Natesan, Subramanian/W-3325-2019
FU Indian Council of Medical Research, New Delhi [45/28/2011-NAN-BMS]
FX We are thankful to Mrs. J. Sridevi, Department of Chemical Physics,
   CLRI, Chennai for assisting in EPR spectrometric analysis. K.
   Venkateshwaran gratefully acknowledges the support of Indian Council of
   Medical Research, New Delhi for granting senior research fellowship
   (45/28/2011-NAN-BMS).
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NR 60
TC 17
Z9 17
U1 4
U2 55
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0928-4931
EI 1873-0191
J9 MAT SCI ENG C-MATER
JI Mater. Sci. Eng. C-Mater. Biol. Appl.
PD AUG 1
PY 2017
VL 77
BP 935
EP 946
DI 10.1016/j.msec.2017.03.179
PG 12
WC Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Materials Science
GA EX6VW
UT WOS:000403381200106
PM 28532114
DA 2022-11-30
ER

PT J
AU Koss, MJ
   Falabella, P
   Stefanini, FR
   Pfister, M
   Thomas, BB
   Kashani, AH
   Brant, R
   Zhu, DH
   Clegg, DO
   Hinton, DR
   Humayun, MS
AF Koss, Michael J.
   Falabella, Paulo
   Stefanini, Francisco R.
   Pfister, Marcel
   Thomas, Biju B.
   Kashani, Amir H.
   Brant, Rodrigo
   Zhu, Danhong
   Clegg, Dennis O.
   Hinton, David R.
   Humayun, Mark S.
TI Subretinal implantation of a monolayer of human embryonic stem
   cell-derived retinal pigment epithelium: a feasibility and safety study
   in Yucatan minipigs
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Human embryonic stem cells; Retinal pigment epithelium; Macular
   degeneration; Preclinical trial; Animal model
ID MACULAR DEGENERATION; BRUCHS MEMBRANE; TRANSPLANTATION; RPE;
   DIFFERENTIATION; DETACHMENT; SURVIVAL; TRANSLOCATION; PIG
AB A subretinal implant termed CPCB-RPE1 is currently being developed to surgically replace dystrophic RPE in patients with dry age-related macular degeneration (AMD) and severe vision loss. CPCB-RPE1 is composed of a terminally differentiated, polarized human embryonic stem cell-derived RPE (hESC-RPE) monolayer pre-grown on a biocompatible, mesh-supported submicron parylene C membrane. The objective of the present delivery study was to assess the feasibility and 1-month safety of CPCB-RPE1 implantation in Yucatan minipigs, whose eyes are similar to human eyes in size and gross retinal anatomy.
   This was a prospective, partially blinded, randomized study in 14 normal-sighted female Yucatan minipigs (aged 2 months, weighing 24-35 kg). Surgeons were blinded to the randomization codes and postoperative and post-mortem assessments were performed in a blinded manner. Eleven minipigs received CPCB-RPE1 while three control minipigs underwent sham surgery that generated subretinal blebs. All animals except two sham controls received combined local (Ozurdex (TM) dexamethasone intravitreal implant) and systemic (tacrolimus) immunosuppression or local immunosuppression alone. Correct placement of the CPCB-RPE1 implant was assessed by in vivo optical coherence tomography and post-mortem histology. hESC-RPE cells were identified using immunohistochemistry staining for TRA-1-85 (a human marker) and RPE65 (an RPE marker). As the study results of primary interest were nonnumerical no statistical analysis or tests were conducted.
   CPCB-RPE1 implants were reliably placed, without implant breakage, in the subretinal space of the minipig eye using surgical techniques similar to those that would be used in humans. Histologically, hESC-RPE cells were found to survive as an intact monolayer for 1 month based on immunohistochemistry staining for TRA-1-85 and RPE65.
   Although inconclusive regarding the necessity or benefit of systemic or local immunosuppression, our study demonstrates the feasibility and safety of CPCB-RPE1 subretinal implantation in a comparable animal model and provides an encouraging starting point for human studies.
C1 [Koss, Michael J.] Heidelberg Univ, Dept Ophthalmol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
   [Koss, Michael J.; Falabella, Paulo; Pfister, Marcel; Thomas, Biju B.; Kashani, Amir H.; Zhu, Danhong; Hinton, David R.; Humayun, Mark S.] Univ Southern Calif, USC Eye Inst, 1450 San Pablo St, Los Angeles, CA 90033 USA.
   [Stefanini, Francisco R.; Brant, Rodrigo] Univ Fed Sao Paulo, UNIFESP, Dept Ophthalmol, Rua Botucatu 821, BR-04023062 Sao Paulo, Brazil.
   [Zhu, Danhong; Hinton, David R.] Univ Southern Calif, Keck Sch Med, Dept Pathol, 1450 San Pablo St, Los Angeles, CA 90033 USA.
   [Clegg, Dennis O.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
   [Humayun, Mark S.] Univ Southern Calif, Inst Biomed Therapeut, 1450 San Pablo St, Los Angeles, CA 90033 USA.
C3 Ruprecht Karls University Heidelberg; University of Southern California;
   Universidade Federal de Sao Paulo (UNIFESP); University of Southern
   California; University of California System; University of California
   Santa Barbara; University of Southern California
RP Koss, MJ (通讯作者)，Heidelberg Univ, Dept Ophthalmol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany.; Koss, MJ (通讯作者)，Univ Southern Calif, USC Eye Inst, 1450 San Pablo St, Los Angeles, CA 90033 USA.
EM michael.koss@me.com
RI Fernandes, Rodrigo/GWV-4158-2022; Brant, Rodrigo/AAR-1878-2021; Brant,
   Rodrigo/CAE-3286-2022
OI Brant, Rodrigo/0000-0002-0274-0315; Brant, Rodrigo/0000-0002-0274-0315;
   Falabella, Paulo/0000-0001-8773-7168
FU California Institute for Regenerative Medicine [DR1-01444, TG2-01161,
   TG2-01151, CL1-00521, FA1-00616]; U.S. National Institutes of Health
   [EY03040]; Research to Prevent Blindness; Arnold and Mabel Beckman
   Foundation; Beatrice Apple Revocable Living Trust; Garland Initiative
   for Vision; Foundation Fighting Blindness Wynn-Gund Translational
   Research Acceleration Program; UCSB Institute for Collaborative
   Biotechnologies from the U.S. Army Research Office [W911NF-09-0001];
   German Research Foundation (DFG), Bonn, Germany [DFG Ko4294/1-1]
FX The California Institute for Regenerative Medicine provided financial
   support in the form of grant funding (DR1-01444, TG2-01161, TG2-01151,
   CL1-00521, and FA1-00616). The U.S. National Institutes of Health
   provided financial support in the form of grant funding (NIH Core Grant
   EY03040). Research to Prevent Blindness, The Arnold and Mabel Beckman
   Foundation, The Beatrice Apple Revocable Living Trust, The Garland
   Initiative for Vision, The Foundation Fighting Blindness Wynn-Gund
   Translational Research Acceleration Program, and the UCSB Institute for
   Collaborative Biotechnologies provided financial support through grant
   W911NF-09-0001 from the U.S. Army Research Office. The content of the
   information does not necessarily reflect the position or the policy of
   the U.S. Government, and no official endorsement should be inferred. The
   German Research Foundation (DFG), Bonn, Germany provided financial
   support in the form of a research fellowship grant to Michael J. Koss
   (DFG Ko4294/1-1).
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NR 36
TC 55
Z9 55
U1 0
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD AUG
PY 2016
VL 254
IS 8
BP 1553
EP 1565
DI 10.1007/s00417-016-3386-y
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DS3IB
UT WOS:000380675200014
PM 27335025
OA Green Published
DA 2022-11-30
ER

PT J
AU Tong, Y
   Zhao, KK
   Feng, D
   Biswal, M
   Zhao, PQ
   Wang, ZY
   Zhang, Y
AF Tong, Yao
   Zhao, Ke-Ke
   Feng, Dong
   Biswal, Manas
   Zhao, Pei-Quan
   Wang, Zhao-Yang
   Zhang, Yun
TI Comparison of the efficacy of anti-VEGF monotherapy versus PDT and
   intravitreal anti -VEGF combination treatment in AMD: a Meta -analysis
   and systematic review
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; anti-vascular endothelial growth
   factor; photodynamic therapy; Meta-analysis
ID VERTEPORFIN PLUS RANIBIZUMAB; MACULAR DEGENERATION; CHOROIDAL
   NEOVASCULARIZATION; PHOTODYNAMIC THERAPY; BEVACIZUMAB; PREVALENCE
AB AIM: To compare the effect of anti-vascular endothelial growth factor (VEGF) monotherapy versus photodynamic therapy (PDT) and anti-VEGF combination treatment in age-related macular degeneration (AMD).
   METHODS: A computerized online search was performed using PubMed, Web of Science and the Cochrane Library. Studies that compared anti -VEGF monotherapy with PDT and anti -VEGF combination treatment of AMD and were designed as randomized controlled trials were included. The means and standard deviations of the best -corrected visual acuity (BCVA), central retinal thickness (CRT), number of treatments and proportions of patients who gained BCVA >= 15, 10, 5, or 0 letters at 12th month were extracted. A systematic review and Meta-analysis of the comparison of the two approaches was conducted using Review Manager 5.2. Subgroup. A sensitivity analysis was also performed.
   RESULTS: Eight studies were included. When the subgroup and sensitivity analysis was conducted, the results indicated that in the findings that included the monotherapy group and PDT (standard fluence, SF) group of Kaiser's study, the patients in the monotherapy group had a better BCVA compared with the combination group at 12th month in the PDT (SF) subgroup [weighted mean difference (WMD): 3.54; 95% CI: 0.36 to 6.73; P=0.03], and there were more patients who gained >= 15 letters of BCVA in the monotherapy group compared with the combination group in the total result [odds ratio (OR): 1.41; 95% CI: 1.02 to 1.95; P=0.04]. The same conclusion was obtained in the total result that included the monotherapy group and PDT (reduced fluence, RF) group of Kaiser's study (OR: 1.56; 95% CI: 1.13 to 2.15; P=0.007). However, there were no significant differences in the other indexes between the two therapies.
   CONCLUSION: We found that anti-VEGF monotherapy is more effective on the recovery of visual acuity than combination therapy and more researches with lager sample size should be performed to study on the effect of the two therapy approaches on CRT and number of injections.
C1 [Tong, Yao; Zhang, Yun] Wenzhou Med Univ, Hosp Eye, Wenzhou 325027, Zhejiang, Peoples R China.
   [Tong, Yao; Zhao, Pei-Quan; Wang, Zhao-Yang] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Ophthalmol, Shanghai 200092, Peoples R China.
   [Zhao, Ke-Ke] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Dept Ophthalmol, Shanghai 200127, Peoples R China.
   [Feng, Dong] Zhejiang Univ, Coll Med, Affiliated Hosp 1, Dept Ophthalmol, Hangzhou 310006, Zhejiang, Peoples R China.
   [Biswal, Manas] Univ Florida, Dept Mol Genet, Gainesville, FL 32610 USA.
C3 Wenzhou Medical University; Shanghai Jiao Tong University; Shanghai Jiao
   Tong University; Zhejiang University; State University System of
   Florida; University of Florida
RP Zhang, Y (通讯作者)，Wenzhou Med Univ, Hosp Eye, Wenzhou 325027, Zhejiang, Peoples R China.; Wang, ZY (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Ophthalmol, Shanghai 200092, Peoples R China.
EM zhaokekewzy@hotmail.com; 15869153053@163.com
OI Biswal, Manas/0000-0002-9685-2923
FU National Natural Science Funds of China [81371040]; Shanghai Pujiang
   Program [15PJD028]
FX Supported by the National Natural Science Funds of China (No. 81371040);
   Shanghai Pujiang Program (No. 15PJD028).
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NR 20
TC 13
Z9 13
U1 0
U2 14
PU IJO PRESS
PI XI AN
PA NO 269 YOUYI EAST RD, XI AN, 710054, PEOPLES R CHINA
SN 2222-3959
EI 2227-4898
J9 INT J OPHTHALMOL-CHI
JI Int. J. Ophthalmol.
PD JUL 18
PY 2016
VL 9
IS 7
BP 1028
EP 1037
DI 10.18240/ijo.2016.07.16
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DT2XR
UT WOS:000381345600017
PM 27500113
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Guo, XL
   Zhu, DL
   Lian, RL
   Han, YT
   Guo, YL
   Li, ZJ
   Tang, SB
   Chen, JS
AF Guo, Xiaoling
   Zhu, Deliang
   Lian, Ruiling
   Han, Yuting
   Guo, Yonglong
   Li, Zhijie
   Tang, Shibo
   Chen, Jiansu
TI Matrigel and Activin A promote cell-cell contact and anti-apoptotic
   activity in cultured human retinal pigment epithelium cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Human retinal pigmented epithelium; Matrigel; Activin A; Cell-cell
   contact; Anti-apoptosis
ID PLURIPOTENT STEM-CELLS; MESENCHYMAL TRANSITION; BETA-CATENIN;
   PROLIFERATIVE VITREORETINOPATHY; MACULAR DEGENERATION;
   EXTRACELLULAR-MATRIX; ADHESION MOLECULES; JUNCTIONAL COMPLEX; BARRIER
   PROPERTIES; SIGNALING PATHWAY
AB Age-related macular degeneration (AMD) is a leading cause of blindness among the aging population. Currently, replacement of diseased retinal pigment epithelium (RPE) cells with transplanted healthy RPE cells could be a feasible approach for AMD therapy. However, maintaining cell-cell contact and good viability of RPE cells cultured in vitro is difficult and fundamentally determines the success of RPE cell transplantation. This study was conducted to examine the role of Matrigel and Activin A (MA) in regulating cell-cell contact and anti-apoptotic activity in human RPE (hRPE) cells, as assessed by atomic force microscopy (AFM), scanning electron microscope (SEM), immunofluorescence staining, quantitative polymerase chain reaction (qPCR) analysis, Annexin V/propidium iodide (PI) analysis, mitochondria] membrane potential (PT m) assays, intracellular reactive oxygen species (ROS) assays and Western blotting. hRPE cells cultured in vitro could maintain their epithelioid morphology after MA treatment over at least 4 passages. The contact of N-cadherin to the lateral cell border was promoted in hRPE cells at P2 by MA. MA treatment also enhanced the expression of tight junction-associated genes and proteins, such as Claudin-1, Claudin-3, Occludin and ZO-1, as well as polarized ZO-1 protein distribution and barrier function, in cultured hRPE cells. Moreover, MA treatment decreased apoptotic cells, ROS and Bax and increased AW m and Bcl2 in hRPE cells under serum withdrawal-induced apoptosis. In addition, MA treatment elevated the protein expression levels of 13-catenin and its target proteins, including Cyclin D1, c-Myc and Survivin, as well as the gene expression levels of ZO-1, 0-catenin, Survivin and TCF-4, all of which could be down-regulated by the Wnt/6-catenin pathway inhibitor XAV-939. Taken together, MA treatment could effectively promote cell-cell contact and anti-apoptotic activity in hRPE cells, partly involving the Wnt/fl-catenin pathway. This study will benefit the understanding of hRPE cells and future cell therapy. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Guo, Xiaoling; Zhu, Deliang; Guo, Yonglong; Chen, Jiansu] Jinan Univ, Minist Educ, Key Lab Regenerat Med, Guangzhou 510632, Guangdong, Peoples R China.
   [Li, Zhijie; Chen, Jiansu] Jinan Univ, Coll Med, Inst Ophthalmol, West Huangpu Ave 601, Guangzhou 510632, Guangdong, Peoples R China.
   [Lian, Ruiling; Han, Yuting; Chen, Jiansu] Jinan Univ, Clin Med Coll 1, Dept Ophthalmol, Guangzhou 510632, Guangdong, Peoples R China.
   [Tang, Shibo] Cent S Univ, Aier Sch Ophthalmol, Furong Middle Rd 198, Changsha 410015, Hunan, Peoples R China.
C3 Jinan University; Jinan University; Jinan University; Central South
   University
RP Chen, JS (通讯作者)，Jinan Univ, Coll Med, Inst Ophthalmol, West Huangpu Ave 601, Guangzhou 510632, Guangdong, Peoples R China.; Tang, SB (通讯作者)，Cent S Univ, Aier Sch Ophthalmol, Furong Middle Rd 198, Changsha 410015, Hunan, Peoples R China.
EM tangsb@mail.sysu.edu.cn; chenjiansu2000@163.com
RI Han, Yu/GZA-9220-2022; Guo, Xiaoling/AAJ-2958-2020; TANG,
   Shi/GXH-5719-2022
OI Chen, Jiansu/0000-0001-6703-9573
FU National Natural Science Foundation of China [81371689]; Ministry of
   Science and Technology [2012DFH30060]; Special Funds for Major Science
   and Technology Projects of Guangdong Province [2015B010125007]
FX We would like to thank Professor Yang Xiao of Aier School of
   Ophthalmology, Central South University, for help in the revision of the
   manuscripts. This work was supported by the National Natural Science
   Foundation of China (No. 81371689), a collaborated grant for HK-Macao-TW
   from the Ministry of Science and Technology (2012DFH30060) and Special
   Funds for Major Science and Technology Projects of Guangdong Province
   (2015B010125007).
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NR 54
TC 10
Z9 11
U1 1
U2 38
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUN
PY 2016
VL 147
BP 37
EP 49
DI 10.1016/j.exer.2016.04.021
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DP0NP
UT WOS:000378186800005
PM 27130547
DA 2022-11-30
ER

PT J
AU Reznicek, L
   Muhr, J
   Ulbig, M
   Kampik, A
   Mayer, WJ
   Haritoglou, C
   Neubauer, A
   Wolf, A
AF Reznicek, Lukas
   Muhr, Johanna
   Ulbig, Michael
   Kampik, Anselm
   Mayer, Wolfgang J.
   Haritoglou, Christos
   Neubauer, Aljoscha
   Wolf, Armin
TI Visual acuity and central retinal thickness: fulfilment of retreatment
   criteria for recurrent neovascular AMD in routine clinical care
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; RANIBIZUMAB TREATMENT; CHOROIDAL
   NEOVASCULARIZATION; BEVACIZUMAB; EFFICACY; TRIAL; SERVICES
AB Background To evaluate the fulfilment of retreatment criteria in recurrent neovascular age-related macular degeneration (nAMD) for a pro-re-nata treatment regime with ranibizumab in routine clinical care.
   Methods Data from patients with treatment-naive nAMD were analysed retrospectively. As an 'upload', all patients had received three-monthly intravitreal ranibizumab injections in a university eye hospital and were then seen by ophthalmologists in private practice who referred them back in case of recurrence. Recurrence was defined as a decrease of visual acuity (VA) of one line or more (functional retreatment criteria), a central retinal thickness (CRT) increase of at least 100 mm upon Optical Coherence Tomography (OCT) examination (morphological retreatment criteria) or a new macular haemorrhage (clinical retreatment criteria).
   Results We included 92 patients (36 men and 56 women). The mean VA before retreatment of a recurrence was -0.63 +/- 0.33 logMAR and improved significantly (p<0.001) by 0.10 +/- 0.16 logMAR to -0.53 +/- 0.28 logMAR thereafter. Mean CRT before retreatment was 278.07 +/- 87.56 mu m and decreased significantly (p<0.001) by 71.22 +/- 106.93 to 206.85 +/- 60.30 mu m. Evaluation of the fulfilment of retreatment criteria revealed functional retreatment criteria in 82.6% of patients. However, upon re-evaluation of VA using Early Treatment Diabetic Retinopathy Study (ETDRS) charts in the treatment centre, mean decrease of VA was 10 letters as compared with the end of upload therapy. All patients presented an increased CRT when treated for recurrence of nAMD (mean increase 69.47 mu m), but the morphological retreatment criteria (CRT increase of 100 mu m or more) were fulfilled in only 44.4% of patients upon Spectral Domain OCT (SD-OCT) evaluation in the treatment centre.
   Conclusions In a routine clinical care, evaluation of VA using ETDRS charts seems to be more sensitive than Snellen VA testing. Quantitative OCT-based retreatment criteria (eg, increase of CRT of 100 mm or more) appear to be not sensitive enough in a clinical setting with referring ophthalmologists.
C1 [Reznicek, Lukas; Muhr, Johanna; Ulbig, Michael; Kampik, Anselm; Mayer, Wolfgang J.; Haritoglou, Christos; Neubauer, Aljoscha; Wolf, Armin] Univ Munich, Dept Ophthalmol, D-80336 Munich, Germany.
C3 University of Munich
RP Reznicek, L (通讯作者)，Univ Munich, Klinikum Univ Munchen, Dept Ophthalmol, Campus Innenstadt,Mathildenstr 8, D-80336 Munich, Germany.
EM Lukas.Reznicek@med.uni-muenchen.de
RI Mayer, Wolfgang/AAJ-1407-2020
OI Mayer, Wolfgang/0000-0001-8891-4875
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NR 26
TC 9
Z9 9
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD OCT
PY 2014
VL 98
IS 10
BP 1333
EP 1337
DI 10.1136/bjophthalmol-2013-304399
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AQ3HF
UT WOS:000342681400007
PM 24903670
OA Green Published
DA 2022-11-30
ER

PT J
AU Horsley, MB
   Mandava, N
   Maycotte, MA
   Kahook, MY
AF Horsley, Michael B.
   Mandava, Naresh
   Maycotte, Marco A.
   Kahook, Malik Y.
TI Retinal Nerve Fiber Layer Thickness in Patients Receiving Chronic
   Anti-Vascular Endothelial Growth Factor Therapy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID INTRAOCULAR-PRESSURE CHANGES; INTRAVITREAL INJECTIONS; BEVACIZUMAB
   AVASTIN; MACULAR THICKNESS; FACTOR AGENTS; STRATUS OCT; GLAUCOMA;
   REPRODUCIBILITY; PROGRESSION; PEGAPTANIB
AB PURPOSE: To evaluate the effects of multiple intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents on the thickness of the retinal nerve fiber layer (RNFL) in patients with wet age-related macular degeneration (ARMD).
   DESIGN: Retrospective, observational, consecutive case series of patients diagnosed with wet ARMD.
   METHODS: Forty-one eyes of 37 consecutive patients (25 female and 12 male; mean age 79.2 +/- 8.7 years) who underwent treatment with pegaptanib, bevacizumab, and/or ranibizumab for ARMD followed by sequential RNFL thickness measurement by optical coherence tomography (OCT) were studied. Patients were included in the analyses if they had greater than 10 total anti-VEGF injections, RNFL measurements prior to the first injection, and at least 12 months of follow-up. Patients were divided into 3 groups depending on which anti-VEGF agent(s) they received. The OCT RNFL measurements at the initial and final follow-up were used for analyses.
   RESULTS: Average follow-up for all patients was 27.0 +/- 9.7 months and they received an average of 16.0 +/- 5.5 intravitreal injections. The average RNFL thickness at presentation was 92.4 +/- 15.2 mu m and at last follow-up was 93.8 +/- 15.2 mu m (P = .68). There were no statistically significant differences in RNFL measurements when comparing between individual anti-VEGF treatment groups.
   CONCLUSION: Long-term treatment with anti-VEGF agents did not lead to significant changes in RNFL thickness in a patient population with wet ARMD. Despite the possibility of repeated intraocular pressure (IOP) fluctuations after intravitreal injections and known neurotrophic properties of VEGF in the eye, chronic therapy with intravitreal anti-VEGF agents does not appear to adversely affect RNFL thickness. Further prospective studies with longer follow-up are needed to corroborate the findings of this study. (Am J Ophthalmol 2010;150:558-561. (C) 2010 by Elsevier Inc. All rights reserved.)
C1 [Horsley, Michael B.; Mandava, Naresh; Maycotte, Marco A.; Kahook, Malik Y.] Univ Colorado Denver, Rocky Mt Lions Eye Inst, Dept Ophthalmol, Aurora, CO 80045 USA.
C3 Children's Hospital Colorado; University of Colorado System; University
   of Colorado Anschutz Medical Campus
RP Kahook, MY (通讯作者)，Univ Colorado Denver, Rocky Mt Lions Eye Inst, Dept Ophthalmol, 1675 Aurora Court,Mail Stop F-731, Aurora, CO 80045 USA.
EM Malik.Kahook@gmail.com
FU Genentech, San Francisco, California; Alcon, AGS, the State of Colorado,
   and Genentech
FX NO GOVERNMENT OR NONGOVERNMENT SUPPORT WAS RECEIVED FOR THIS STUDY.
   NARESH MANDAVA RECEIVED GRANT support from Genentech, San Francisco,
   California. Malik Kahook received grant support from Alcon, AGS, the
   State of Colorado, and Genentech; is a consultant for Alcon, Allergan,
   VRT, and Merck; and received lecture fees from Alcon, Endo Optiks,
   Merck, and Genentech. Involved in design of the study (M.H., N.M.,
   M.K.), conduct of the study (M.H., N.M., M.M., M.K.), collection of data
   (M.H., MM.), management of data (M.H., N.M., M.K.), analysis and
   interpretation of the data (M.H., N.M., M.K.), preparation of the
   manuscript (M.H., N.M., M.K.), and review and approval of the manuscript
   (M.H., N.M., M.K.). IRB approval was obtained through the Colorado
   Multiple Institutional Review Board. This study is in compliance with
   HIPAA regulations.
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NR 21
TC 63
Z9 69
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD OCT
PY 2010
VL 150
IS 4
BP 558
EP 561
DI 10.1016/j.ajo.2010.04.029
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 663FD
UT WOS:000282867500018
PM 20643396
DA 2022-11-30
ER

PT J
AU Jiang, CT
   Xiong, W
   Lu, BY
   Gonda, MA
   Chang, JY
AF Jiang, Chuantao
   Xiong, Wei
   Lu, Bao-Yuan
   Gonda, Matthew A.
   Chang, Jui-Yoa
TI Synthesis and Immune Response of Non-native Isomers of Vascular
   Endothelial Growth Factor
SO BIOCHEMISTRY
LA English
DT Article
ID PROTEIN DISULFIDE-ISOMERASE; CYCLIC CYSTINE KNOT; CELL LUNG-CANCER;
   TUMOR ANGIOGENESIS; SCRAMBLED ISOMERS; CRYSTAL-STRUCTURE; BEVACIZUMAB;
   RECEPTOR; INHIBITOR; PEPTIDE
AB Native proteins often lack immunogenicity and thus limit vaccine and mAb development. We described here a unique method to enhance the immunogenicity of native proteins. This is achieved by creating non-native isomers of disulfide proteins (X-isomers) using the method of disulfide scrambling. X-isomers have the potential to be developed as vaccines and effective immunogens, as they are capable of breaking the immune tolerance and eliciting antibodies that cross-react with the native protein. In this report, we describe production of X-isomers of vascular endothelial growth factor (X-VEGF). The aim is to develop X-VEGF for cancer immunotherapy targeting reduction of VEGF. The production of mouse X-VEGF is achieved by expressing the short version of VEGF (1 - 110) commonly shared by all VEGF isoforms, with two Cys double right arrow Ala mutations at Cys(51) and Cys(60) to generate R-VEGF(110) (R stands for fully reduced). R-VEGF(110) was then allowed to undergo oxidative folding in the absence of denaturant to form N-VEGF(110) (N stands for native) or in the presence of denaturant to generate five fractions of X-VEGF(110) isomers. While N-VEGF(110) exhibits only marginal immunogenicity in mice, all five fractions of X-VEGF(110) isomers were shown to elicit high titers of antibodies that cross-react with N-VEGF(110). In sera of immunized mice, the amounts of anti-N-VEGF antibodies elicited by X-VEGF(110) isomers range from 54 to 186 mu g/mL, which are compatible with or greater than the concentration required for effective therapy using anti-VEGF MAbs. The underlying mechanism of enhanced immunogenicity of X-VEGF(110) is investigated and elaborated. These data suggest that X-VEGF(110) isomers are potential compounds in developing active immunotherapy for treatment of VEGFR bearing tumors and the wet form of age-related macular degeneration.
C1 [Jiang, Chuantao; Xiong, Wei; Lu, Bao-Yuan; Chang, Jui-Yoa] Univ Texas Houston, Res Ctr Prot Chem, Brown Fdn Inst Mol Med, Houston, TX 77030 USA.
   [Jiang, Chuantao; Xiong, Wei; Lu, Bao-Yuan; Chang, Jui-Yoa] Univ Texas Houston, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Gonda, Matthew A.] IsoVax Technol Inc, Houston, TX 77030 USA.
C3 University of Texas System; University of Texas Health Science Center
   Houston; University of Texas System; University of Texas Health Science
   Center Houston
RP Chang, JY (通讯作者)，Univ Texas Houston, Res Ctr Prot Chem, Brown Fdn Inst Mol Med, Houston, TX 77030 USA.
EM Rowen.Chang@uth.tmc.edu
FU IsoVax Therapeutics; Robert Welch foundation
FX J.-Y.C. acknowledges the support from Protein Institute Inc. (now IsoVax
   Therapeutics) and the endowment from the Robert Welch foundation.
   J.-Y.C. is a stock holder of IsoVax Technologies.
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NR 36
TC 8
Z9 10
U1 1
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD AUG 10
PY 2010
VL 49
IS 31
BP 6550
EP 6556
DI 10.1021/bi100815n
PG 7
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 636NE
UT WOS:000280743200006
PM 20575515
DA 2022-11-30
ER

PT J
AU Satarug, S
   Kikuchi, M
   Wisedpanichkij, R
   Li, B
   Takeda, K
   Na-Bangchang, K
   Moore, MR
   Hirayama, K
   Shibahara, S
AF Satarug, Soisungwan
   Kikuchi, Mihoko
   Wisedpanichkij, Raewadee
   Li, Bin
   Takeda, Kazuhisa
   Na-Bangchang, Kesara
   Moore, Michael R.
   Hirayama, Kenji
   Shibahara, Shigeki
TI Prevention of cadmium accumulation in retinal pigment epithelium with
   manganese and zinc
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-relate macular degeneration; cadmium; heme oxygenase; manganese;
   metal transporters; retinal pigment epithelium; Solute-Carrier 39
   protein; SLC39; zinc; ZIP8; ZIP14
ID HEME OXYGENASE-1 GENE; MICROSATELLITE POLYMORPHISM; METALLOTHIONEIN IIA;
   TRANSPORT-SYSTEM; URINARY CADMIUM; CELL LINE; AGE; EXPRESSION; EXPOSURE;
   PROMOTER
AB Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly. Risk factors include old age, female gender, obesity, smoking, low dietary intakes of antioxidants and increased exposure to the toxic metal cadmium (Cd2+). Supplementation with high-dose zinc (80 mg) provides some protection, but the mechanism(S) underlying such protection has not been fully elucidated. The present study had a focus on the human retinal pigment epithelial (RPE) cell line ARPE-19 in an attempt to demonstrate a reduction in intracellular Cd2+ effect associated with heme oxygenase-1 (HO-1) expression by co-exposure with zinc (Zn2+) or manganese (Mn2+), which is known to be a more potent inhibitor of Cd2+, uptake than Zn2+. Our results indicated that co-exposure of 10 mu M Cd2+ with 5 mu M Mn2+ reduced the intracellular Cd2+ effect by 50-60%, possibly by limiting the amounts of Cd2+ entering cells through Mn2+ transporter protein (ZIP8). A similar reduction in a Cd2+ effect was achieved by co-exposure with 20 mu M Zn2+ while co-exposure with 5 and 10 mu M Zn2+ ions was ineffective. Mn 21 ions as low as 2.5 mu M were found to cause an increase in HO-1 mRNA expression levels in ARPE-19 cells, demonstrating for the first time that Mn2+ is an inducer of HO-1. Mn2+ ions at 1 mu M induced HO-1 mRNA expression in the HEK293 human embryonic kidney cells. In contrast, Zn2+, in 5, 10 or 20 mu M concentrations did not induce expression of HO-1 in ARPE-19 cells or any other cells tested. These data suggest the superiority of Mn2+ over Zn2+ in preventing Cd2+ uptake and accumulation in RPE to toxic levels. Further, induction of HO-1 by Mn2+ could provide RPE with some resistance to enhanced oxidative stress arising from Cd2+ accumulation in RPE as HO-1 is one of the frontline cellular antioxidant defense mechanisms. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Satarug, Soisungwan; Moore, Michael R.] Univ Queensland, Natl Res Ctr Environm Toxicol EnTox, Brisbane, Qld, Australia.
   [Satarug, Soisungwan; Wisedpanichkij, Raewadee; Na-Bangchang, Kesara] Thammasat Univ, Fac Allied Hlth Sci, Grad Program Biomed Sci, Pathum Thani, Thailand.
   [Kikuchi, Mihoko] Nagasaki Univ, Ctr Int Collaborat Res, Nagasaki 852, Japan.
   [Kikuchi, Mihoko; Hirayama, Kenji] Nagasaki Univ, Dept Immunogenet, Inst Trop Med, Nagasaki 852, Japan.
   [Satarug, Soisungwan; Wisedpanichkij, Raewadee; Li, Bin; Takeda, Kazuhisa; Shibahara, Shigeki] Tohoku Univ, Sch Med, Dept Mol Biol & Appl Physiol, Sendai, Miyagi 980, Japan.
C3 University of Queensland; Thammasat University; Nagasaki University;
   Nagasaki University; Tohoku University
RP Satarug, S (通讯作者)，Univ N Dakota, Sch Med & Hlth Sci, Dept Pathol, 501 N Columbia Rd,POB 9037, Grand Forks, ND 58202 USA.
EM satarug@yahoo.com
RI Moore, Michael R/C-4163-2012; Shibahara, Shigeki/M-3644-2014; Hirayama,
   Kenji/AAN-7065-2021
OI Moore, Michael R/0000-0002-7012-9534; Hirayama,
   Kenji/0000-0001-9467-1777
FU Ministry of Education, Science, Sports, and Culture of Japan;
   Cosmetology Foundation; Japan Society for the Promotion of Science
   (JSPS) [L 07568]; Queensland Health; University of Queensland
FX This work was supported in part by Grant-in-Aid for Scientific Research
   on Priority Areas, and the 21st Century COE Program Special Research
   Grant "the Center for Innovative Therapeutic Development for Common
   Diseases" from the Ministry of Education, Science, Sports, and Culture
   of Japan, and by the grant provided by the Cosmetology Foundation. S.
   Satarug (ID NO. L 07568) was supported by the Research Fellowship
   (long-term) from Japan Society for the Promotion of Science (JSPS).
   EnTox is supported by Queensland Health and the University of
   Queensland. We are also grateful to Biomedical Research Core of Tohoku
   University Graduate School of Medicine for allowing us to use various
   facilities.
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NR 50
TC 20
Z9 20
U1 0
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD DEC
PY 2008
VL 87
IS 6
BP 587
EP 593
DI 10.1016/j.exer.2008.09.014
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 385OQ
UT WOS:000261823900013
PM 18948096
DA 2022-11-30
ER

PT J
AU Mohammadpour, M
   Jafarinasab, MR
   Javadi, MA
AF Mohammadpour, M.
   Jafarinasab, M. R.
   Javadi, M. A.
TI Outcomes of acute postoperative inflammation after cataract surgery
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE early onset postoperative inflammation; cataract surgery
ID INTRAOCULAR-LENS IMPLANTATION; SYMPATHETIC OPHTHALMIA; PHACOANAPHYLACTIC
   ENDOPHTHALMITIS; POLY(METHYL METHACRYLATE); SILICONE; UVEITIS;
   PHACOEMULSIFICATION; EXTRACTION; FRAGMENTS; EYES
AB PURPOSE. To determine characteristics and final visual and surgical outcomes of patients who experienced early onset postoperative inflammation after cataract surgery and their early and late complications.
   METHODS. This is a prospective case series of 126 patients out of 1500 cases who underwent cataract surgery and experienced early onset postoperative inflammation during the first 2 weeks after cataract surgery. All the patients received complete ocular examinations at onset of signs and symptoms of inflammation. A total of 110 patients with follow-up examinations between 3 and 30 months after recovery of early onset postoperative inflammation (mean follow-up 11.6 months) were enrolled in the next part of the study to evaluate the final visual and surgical outcomes. Background systemic and ocular diseases, type of surgery, type of intraocular lenses and viscoelastic agent, early and late complications, and final best-corrected visual acuity were studied.
   RESULTS. Among 1500 patients, 126 cases (8.4%) had early onset postoperative inflammation, 64 cases (50.7%) were male, and 62 cases (49.3%) were female. Early complications were posterior synechia in 9 cases (7.1%), pupillary block in 2 cases (1.5%), and acute rise of intraocular pressure in 6 cases (4.7%). Late complications consisted of posterior capsular opacity in 38 cases (34.5%) and cystoid macular edema in 4 cases (3.2%). Peak of signs and symptoms of inflammation was during 2 weeks after surgery and all patients responded well to topical steroids. Final best-corrected visual acuity (BCVA) was 20130 and better in 76 cases (69%), between 20/40 and 20/80 in 24 cases (22%), and less than 20180 in 10 cases (9%). All cases with BCVA less than 20/80 had ocular diseases like choroidal neovascularization scar or age-related macular degeneration, advanced glaucoma, or corneal opacity.
   CONCLUSIONS. Early onset postoperative inflammation causes pain, decreased vision, and patient anxiety in the acute phase but neither decreases final visual acuity nor has any significant or permanent ocular sequels.
C1 Labbafinejad Med Ctr, Ophthalm Res Ctr, Tehran, Iran.
RP Mohammadpour, M (通讯作者)，Labbafinejad Med Ctr, Ophthalm Res Ctr, 9th Boostan,Pasdarn St,Post Box 16666, Tehran, Iran.
EM mahammadpour@yahoo.com
RI Javadi, Mohammad ali/AAW-4750-2020; MOHAMMADPOUR, Mehrdad/E-8571-2011
OI Mohammadpour, Mehrdad/0000-0002-9383-6362
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NR 41
TC 30
Z9 31
U1 0
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1120-6721
EI 1724-6016
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD JAN-FEB
PY 2007
VL 17
IS 1
BP 20
EP 28
DI 10.1177/112067210701700104
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 160ZJ
UT WOS:000245983800004
PM 17294379
DA 2022-11-30
ER

PT J
AU Dhooge, PPA
   Runhart, EH
   Li, CHZ
   Angelino, CMD
   Hoyng, CB
   van der Molen, RG
   den Hollander, AI
AF Dhooge, Patty P. A.
   Runhart, Esmee H.
   Li, Catherina H. Z.
   Angelino, Corrie M. de Kat
   Hoyng, Carel B.
   van der Molen, Renate G.
   den Hollander, Anneke, I
TI Systemic complement activation levels in Stargardt disease
SO PLOS ONE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; MOUSE MODEL;
   LIPOFUSCIN; GENE; ABCR; ACCUMULATION; MUTATIONS; ATROPHY; RARE
AB Purpose Preclinical research provides evidence for the complement system as a potential common pathway in Stargardt disease (STGD1) and age-related macular degeneration (AMD) leading to retinal pigment epithelium (RPE) loss. However, systemic complement activation has not yet been assessed in STGD1 patients. We conducted a cross-sectional case-control study to assess systemic complement activation in STGD1 patients and its association with disease severity. Methods Systemic concentrations of complement component C3 and its degradation product C3d were compared between 80 STGD1 patients and 80 controls that were frequency matched for age and sex. The C3d/C3 ratio was used as parameter of systemic complement activation. Within the STGD1 cohort, we additionally examined the association between the C3d/C3 ratio, demographic and behavioural factors (age, sex, smoking and BMI), and measures of disease severity (age at onset, visual acuity, and area of atrophy). Results The C3d/C3 ratio did not significantly differ between patients (mean C3d/C3 ratio 3.5 +/- 1.4) and controls (mean C3d/C3 ratio 3.6 +/- 1.0), mean difference -0.156 (p = 0.804, independent samples t-test). The overall effect size was 8% (95% confidence interval, 3-15%). Elevated C3d/C3 ratios (>8.1) were found in three patients who all had a concomitant inflammatory condition at the time of blood draw. Within the patient cohort, C3 levels were associated with sex (mean difference -134, p = 0.001, independent samples t-test) and BMI (correlation coefficient 0.463, p<0.001, Spearman's Correlation). Conclusions Systemic complement levels were not elevated in STGD1 patients compared to age and sex matched controls and was not associated with STGD1 severity. Considering the continued absent proof of a systemic contribution of the complement system to RPE loss in STGD1 patients, we hypothesize that complement activation in STGD1 is more likely a local process. In light of upcoming complement-targeted therapies, further studies are needed that measure complement levels in the eye of STGD1 patients.
C1 [Dhooge, Patty P. A.; Runhart, Esmee H.; Li, Catherina H. Z.; Hoyng, Carel B.; den Hollander, Anneke, I] Radboud Univ Nijmegen, Dept Ophthalmol, Med Ctr, Nijmegen, Netherlands.
   [Dhooge, Patty P. A.; Runhart, Esmee H.; Li, Catherina H. Z.] Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.
   [Angelino, Corrie M. de Kat; van der Molen, Renate G.] Radboud Univ Nijmegen, Dept Lab Med, Lab Med Immunol, Med Ctr, Nijmegen, Netherlands.
C3 Radboud University Nijmegen; Radboud University Nijmegen; Radboud
   University Nijmegen
RP den Hollander, AI (通讯作者)，Radboud Univ Nijmegen, Dept Ophthalmol, Med Ctr, Nijmegen, Netherlands.
EM anneke.denhollander@radboudumc.nl
RI Dhooge, Patty/J-7238-2018; van der Molen, Renate G/I-2398-2014
OI Dhooge, Patty/0000-0003-1096-1668; van der Molen, Renate
   G/0000-0003-3113-6587
FU Foundation Fighting Blindness USA [PPA-0517-0717-RAD]
FX Supported by the Foundation Fighting Blindness USA, grant no.
   PPA-0517-0717-RAD (to F.P.M. Cremers, S. Roosing and C.B.H.). The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
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NR 46
TC 3
Z9 3
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 25
PY 2021
VL 16
IS 6
AR e0253716
DI 10.1371/journal.pone.0253716
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA TG9CN
UT WOS:000671694400054
PM 34170959
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Huang, TW
   Kamins, TI
   Chen, ZC
   Wang, BY
   Bhuckory, M
   Galambos, L
   Ho, EL
   Ling, T
   Afshar, S
   Shin, A
   Zuckerman, V
   Harris, JS
   Mathieson, K
   Palanker, D
AF Huang, Tiffany W.
   Kamins, Theodore, I
   Chen, Zhijie Charles
   Wang, Bing-Yi
   Bhuckory, Mohajeet
   Galambos, Ludwig
   Ho, Elton
   Ling, Tong
   Afshar, Sean
   Shin, Andrew
   Zuckerman, Valentina
   Harris, James S.
   Mathieson, Keith
   Palanker, Daniel
TI Vertical-junction photodiodes for smaller pixels in retinal prostheses
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
DE retinal prosthesis; photovoltaics; photodiode; vertical junction;
   visually evoked potential; neural stimulation
AB Objective. To restore central vision in patients with atrophic age-related macular degeneration, we replace the lost photoreceptors with photovoltaic pixels, which convert light into current and stimulate the secondary retinal neurons. Clinical trials demonstrated prosthetic acuity closely matching the sampling limit of the 100 mu m pixels, and hence smaller pixels are required for improving visual acuity. However, with smaller flat bipolar pixels, the electric field penetration depth and the photodiode responsivity significantly decrease, making the device inefficient. Smaller pixels may be enabled by (a) increasing the diode responsivity using vertical p-n junctions and (b) directing the electric field in tissue vertically. Here, we demonstrate such novel photodiodes and test the retinal stimulation in a vertical electric field. Approach. Arrays of silicon photodiodes of 55, 40, 30, and 20 mu m in width, with vertical p-n junctions, were fabricated. The electric field in the retina was directed vertically using a common return electrode at the edge of the device. Optical and electronic performance of the diodes was characterized in-vitro, and retinal stimulation threshold measured by recording the visually evoked potentials in rats with retinal degeneration. Main results. The photodiodes exhibited sufficiently low dark current (<10 pA) and responsivity at 880 nm wavelength as high as 0.51 A W-1, with 85% internal quantum efficiency, independent of pixel size. Field mapping in saline demonstrated uniformity of the pixel performance in the array. The full-field stimulation threshold was as low as 0.057 +/- 0.029 mW mm(-2) with 10 ms pulses, independent of pixel size. Significance. Photodiodes with vertical p-n junctions demonstrated excellent charge collection efficiency independent of pixel size, down to 20 mu m. Vertically oriented electric field provides a stimulation threshold that is independent of pixel size. These results are the first steps in validation of scaling down the photovoltaic pixels for subretinal stimulation.
C1 [Huang, Tiffany W.; Kamins, Theodore, I; Chen, Zhijie Charles; Galambos, Ludwig; Afshar, Sean; Harris, James S.] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
   [Wang, Bing-Yi; Ho, Elton] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Bhuckory, Mohajeet; Ling, Tong; Palanker, Daniel] Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA.
   [Ling, Tong; Zuckerman, Valentina; Palanker, Daniel] Stanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USA.
   [Shin, Andrew] Stanford Univ, Dept Mat Sci & Engn, Stanford, CA 94305 USA.
   [Mathieson, Keith] Univ Strathclyde, Inst Photon, Dept Phys, Glasgow, Lanark, Scotland.
C3 Stanford University; Stanford University; Stanford University; Stanford
   University; Stanford University; University of Strathclyde
RP Huang, TW (通讯作者)，Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
EM thuang13@stanford.edu
RI Ling, Tong/ABH-9358-2020; Mathieson, Keith/G-6308-2011
OI Ling, Tong/0000-0001-9009-7966; Bhuckory, Mohajeet
   Balveer/0000-0002-2824-1899; Wang, Bing-Yi/0000-0001-8336-3285; Huang,
   Tiffany/0000-0003-0486-2567; Chen, Zhijie/0000-0003-2705-065X;
   Mathieson, Keith/0000-0002-9517-8076; Palanker,
   Daniel/0000-0002-0480-3025; Shin, Andrew/0000-0002-9323-189X
FU National Institutes of Health [R01-EY-027786, P30-EY-026877]; Department
   of Defense [W81XWH-19-1-0738]; AFOSR [FA9550-19-1-0402]; Wu Tsai
   Institute of Neurosciences at Stanford; Research to Prevent Blindness;
   National Science Foundation [ECCS-1542152]; Royal Academy of Engineering
   Chair in Emerging Technology
FX We would like to thank Jerome Pons from JH Technologies
   (www.jhtechnologies.com) for their help with sample preparation and SEM
   imaging of the crosssectional view of the pixels shown in figure 5(b).
   Studies supported by the National Institutes of Health (Grants
   R01-EY-027786 and P30-EY-026877), the Department of Defense (Grant
   W81XWH-19-1-0738), AFOSR (Grant FA9550-19-1-0402), Wu Tsai Institute of
   Neurosciences at Stanford, and unrestricted grant from Research to
   Prevent Blindness. Photovoltaic arrays were fabricated at the Stanford
   Nano Shared Facilities (SNSF) and Stanford Nanofabrication Facility
   (SNF), which are supported by the National Science Foundation under
   award ECCS-1542152. K M was supported by a Royal Academy of Engineering
   Chair in Emerging Technology. Part of this work was also performed at
   the Marvell Nanofabrication Laboratory at the University of
   CaliforniaBerkeley and at the Lurie Nanofabrication Facility at the
   University of Michigan.
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NR 57
TC 8
Z9 8
U1 0
U2 8
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1741-2560
EI 1741-2552
J9 J NEURAL ENG
JI J. Neural Eng.
PD JUN
PY 2021
VL 18
IS 3
AR 036015
DI 10.1088/1741-2552/abe6b8
PG 16
WC Engineering, Biomedical; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Neurosciences & Neurology
GA QX7VV
UT WOS:000629553100001
PM 33592588
OA Green Accepted, Green Submitted
DA 2022-11-30
ER

PT J
AU Jia, J
   Qiu, DD
   Lu, CX
   Wang, WG
   Li, N
   Han, YY
   Tong, PF
   Sun, XM
   Wu, M
   Dai, JJ
AF Jia, Jie
   Qiu, Dandan
   Lu, Caixia
   Wang, Wenguang
   Li, Na
   Han, Yuanyuan
   Tong, Pinfen
   Sun, Xiaomei
   Wu, Min
   Dai, Jiejie
TI Transcriptome Analysis of Choroid and Retina From Tree Shrew With
   Choroidal Neovascularization Reveals Key Signaling Moieties
SO FRONTIERS IN GENETICS
LA English
DT Article
DE choroidal neovascularization; transcriptome sequencing; bioinformatics;
   tree shrew; signal transduction
ID DIFFERENTIAL EXPRESSION ANALYSIS; SUBRETINAL NEOVASCULARIZATION;
   IN-VIVO; ANGIOGENESIS; GROWTH; MACROPHAGE; INHIBITOR; COMPLEX; MODEL
AB Pathological neovascularization in choroid, a leading cause of blindness, is a characteristic of many fundus diseases, such as diabetic retinopathy and age-related macular degeneration. The present study aimed to elucidate the key signaling pathways in choroidal neovascularization (CNV) by analyzing the mRNA profiles of choroid and retina in tree shrews with CNV. We induced choroidal angiogenesis by laser photocoagulation in 15 tree shrews and obtained mRNA profiles of their choroids and retinas by high-throughput transcriptome sequencing. Hierarchical cluster analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network analysis, hematoxylin and eosin (HE) staining, CD31 immunohistochemistry (IHC), and reverse transcription quantitative PCR (RT-qPCR) were performed. After laser photocoagulation, we obtained a total of 350 differentially expressed genes (DEGs) in the choroid, including 59 genes in Module-FASN ("ME-FASN") module and 28 genes in Module-RPL ("ME-RPL") module. A total of 69 DEGs in retina, including 20 genes in Module-SLC ("ME-SLC") module. Bioinformatics analysis demonstrated that DEGs in choroid were mainly involved in membrane transport; DEGs in "ME-RPL" were prominent in pathways associated with IgA production, antigen presentation, and cell adhesion molecules (CAMs) signaling. DEGs in "ME-FASN" were involved in fatty acid metabolism and PPAR signaling pathway, while DEGs in "ME-SLC" were involved in GABAergic synapse, neuroactive life receptor interaction, cholinergic synapse, and retrograde endocannabinoid signaling pathway. PPI network analysis demonstrated that the ribosomal protein family genes (RPL31, RPL7, RPL26L1, and RPL19) are key factors of "ME-RPL," acyl-CoA superfamily genes (ACACA, ACAT1, ACAA2, and ACACB) and FASN are key factors of "ME-FASN" and superfamily of solid carrier genes (SLC17A6, SLC32A1, SLC12A5, and SLC6A1) and complement genes (C4A, C3, and C2) are key factors of "ME-SLC." In conclusion, the present study discovered the important signal transductions (fatty acid metabolic pathway and CAMs signaling) and genes (ribosomal protein family and the complement system) in tree shrew CNV. We consider that our findings hold implications in unraveling molecular mechanisms that underlie occurrence and development of CNV.
C1 [Jia, Jie; Qiu, Dandan; Lu, Caixia; Wang, Wenguang; Li, Na; Han, Yuanyuan; Tong, Pinfen; Sun, Xiaomei; Dai, Jiejie] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biol, Kunming, Yunnan, Peoples R China.
   [Jia, Jie] Kunming Med Univ, Sci Res Lab Ctr, Affiliated Hosp 1, Kunming, Yunnan, Peoples R China.
   [Qiu, Dandan] Kunming Med Univ, Kunming, Yunnan, Peoples R China.
   [Wu, Min] Second Peoples Hosp Yunnan, Yunnan Eye Inst, Kunming, Yunnan, Peoples R China.
C3 Chinese Academy of Medical Sciences - Peking Union Medical College;
   Institute of Medical Biology - CAMS; Peking Union Medical College;
   Kunming Medical University; Kunming Medical University
RP Dai, JJ (通讯作者)，Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biol, Kunming, Yunnan, Peoples R China.; Wu, M (通讯作者)，Second Peoples Hosp Yunnan, Yunnan Eye Inst, Kunming, Yunnan, Peoples R China.
EM ynwumin@126.com; djj@imbcams.com.cn
FU Yunnan Key Project of Science and Technology Plan [2019FA028]; Yunnan
   Key Laboratory of Ophthalmic Research and Disease Control [2017DG008];
   Yunnan Science and Technology Talent and Platform Program [2017HC019,
   2018HB071]; Yunnan Health Training Project of High Level Talents
   [D-2018026]; Kunming Science and Technology Innovation Team
   [2019-1-R-24483]
FX This work was supported by Yunnan Key Project of Science and Technology
   Plan (2019FA028), Yunnan Key Laboratory of Ophthalmic Research and
   Disease Control (2017DG008), Yunnan Science and Technology Talent and
   Platform Program (2017HC019 and 2018HB071), Yunnan Health Training
   Project of High Level Talents (D-2018026), and Kunming Science and
   Technology Innovation Team (2019-1-R-24483).
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NR 47
TC 2
Z9 2
U1 6
U2 6
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1664-8021
J9 FRONT GENET
JI Front. Genet.
PD MAY 10
PY 2021
VL 12
AR 654955
DI 10.3389/fgene.2021.654955
PG 14
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA SF9QP
UT WOS:000653081500001
PM 34040635
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Xue, B
   Zhang, SS
   Gan, L
   Lu, WF
   Li, J
AF Xue, Bai
   Zhang, Shanshan
   Gan, Li
   Lu, Weifeng
   Li, Jie
TI A new hand-held holder optimizes the parameters of the laser-induced
   choroidal neovascularization model in mice
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Fixing tool; Laser-induced choroidal neovascularization; Mouse model;
   Age-related macular degeneration
ID ANGIOGENESIS; INJECTION
AB Background: The laser-induced choroidal neovascularization (CNV) mouse model, as the most classic animal model of age-related macular degeneration (AMD), has been widely used. We designed a hand-held mouse holder to optimize mouse fixation in the laser-induced CNV modelling process, which was inconvenient until now. This study aimed to evaluate the effectiveness of our in-house hand-held mouse holder design in the laser-induced CNV mouse modelling process.
   Methods: Six ophthalmic residents were invited to perform laser-induced CNV mouse modelling by hand or using the holder. We compared the learning time of residents and their physical and mental fatigue with the two methods. In addition, we compared the parameters of CNV modelling with two methods by a skilled operator, including the time of photocoagulation, induction rate and uniformity of CNV lesions.
   Results: In the learning phase, the average learning time to master the modelling method was significantly shortened by utilizing the holder. The fatigue in the operation process was quantified to a level from 0 to 4, and the physical fatigue by using holder (0.8 +/- 0.3) was lower than by hand (2.6 +/- 0.4), and the mental fatigue was relieved from 2.3 +/- 0.5 to 0.4 +/- 0.3. On the other hand, the skilled operator can significantly shorten the time of laser photocoagulation from 146.7 +/- 36.0 s to 63.6 +/- 5.7 s and improve the success rate of modelling from 50.0% +/- 8.3%-87.5% +/- 6.7% by using a holder compared to hand. In addition, the standard error of the mean (SEM) of the distance between the CNV lesion and the optic nerve (ON) and the distance between each lesion was reduced.
   Conclusion: This hand-held mouse holder could optimize the setting and conditions of laser-induced CNV mouse modelling by improving the learning curve, reducing fatigue, shortening the time for photocoagulation, improving the success rate and consistency of laser-induced lesions.
C1 [Xue, Bai; Zhang, Shanshan; Gan, Li] Univ Elect Sci & Technol China, Inst Lab Med, Sichuan Prov Key Lab Human, Dis Gene Study,Sichuan Prov Peoples Hosp,Sch Med, Chengdu 610054, Peoples R China.
   [Li, Jie] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Ophthalmol, 32,West Sect 2,1st Ring Rd, Chengdu 610072, Sichuan, Peoples R China.
   [Lu, Weifeng] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Anesthesia Operat Ctr, Chengdu 610072, Peoples R China.
C3 Sichuan Provincial People's Hospital; University of Electronic Science &
   Technology of China; Sichuan Provincial People's Hospital; University of
   Electronic Science & Technology of China; Sichuan Provincial People's
   Hospital; University of Electronic Science & Technology of China
RP Li, J (通讯作者)，Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Ophthalmol, 32,West Sect 2,1st Ring Rd, Chengdu 610072, Sichuan, Peoples R China.; Lu, WF (通讯作者)，Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Anesthesia Operat Ctr, Chengdu 610072, Peoples R China.
EM 785252430@qq.com; doctorjacklee@163.com
OI Xue, Bai/0000-0002-8838-2167
FU National Natural Science Foundation of China [81700841]
FX This study was funded by the National Natural Science Foundation of
   China, grant number 81700841.
CR Bogdanovich S, 2016, SIGNAL TRANSDUCT TAR, V1, DOI 10.1038/sigtrans.2015.1
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NR 25
TC 1
Z9 1
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2021
VL 203
AR 108392
DI 10.1016/j.exer.2020.108392
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QH2VG
UT WOS:000618134800002
PM 33338490
DA 2022-11-30
ER

PT J
AU Fragiotta, S
   Fernandez-Avellaneda, P
   Breazzano, MP
   Yannuzzi, LA
   Curcio, CA
   Freund, KB
AF Fragiotta, Serena
   Fernandez-Avellaneda, Pedro
   Breazzano, Mark P.
   Yannuzzi, Lawrence A.
   Curcio, Christine A.
   Freund, K. Bailey
TI Linear and planar reflection artifacts on swept-source and
   spectral-domain optical coherence tomography due to hyperreflective
   crystalline deposits
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Hyperreflective crystalline deposits; Cholesterol; Crystals; Age-related
   macular degeneration; Spectral-domain optical coherence tomography;
   Swept-source optical coherence tomography
ID RETINAL ASTROCYTIC HAMARTOMA; CHOLESTEROL CRYSTALS; GEOGRAPHIC ATROPHY;
   TWINKLING ARTIFACT; AGE; DRUSEN; EVOLUTION; PLAQUES; ANGIOGRAPHY;
   SONOGRAPHY
AB Purpose To describe novel spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) linear and planar reflection artifacts produced by hyperreflective crystalline deposits (HCD). Methods Imaging from 10 eyes with HCD producing linear and planar artifacts on OCT was retrospectively analyzed. All eyes had SD-OCT (Spectralis HRA + OCT, Heidelberg Engineering, Germany) and SS-OCT angiography (PLEX Elite 9000, Carl Zeiss Meditec, Inc., Dublin, CA) acquired on the same day. The horizontal extent of planar artifacts and the corresponding HCD on B-scans was measured using a digital caliper. Artifact features from HCD in eyes with non-neovascular age-related macular degeneration (AMD) were analyzed and compared to those seen in two eyes with the "onion sign," an OCT signature previously shown to represent cholesterol crystals (CC) in the sub-retinal pigment epithelium-basal laminar space of eyes with neovascular AMD. A third eye with the "onion sign" was imaged with dense B-scan (DB)-OCTA. Results Ten eyes of ten patients (77.4 +/- 8.7 years) with HCD were analyzed. On SS-OCTA, HCD produced linear artifacts of high signal intensity passing through the HCD and spanning the entire scan depth. On SD-OCT, HCD produced planar artifacts located anterior to both the retina and a hyporeflective space representing normal vitreous signal. The horizontal extent of the artifact did not differ significantly from the corresponding HCD on OCT B-scans (P = 0.62). The OCT artifacts produced by the "onion sign" appeared similar to those of HCD. The additional eye with neovascular AMD imaged with DB-OCTA was characterized by a single, vertical, linear false-flow signal crossing retinal layers. Conclusions To the authors' knowledge, this is the first description of SD- and SS-OCT/OCTA artifacts corresponding to both HCD and the "onion sign." These artifacts are likely due to highly reflective CC previously shown on histology to correspond to both of these OCT signatures.
C1 [Fragiotta, Serena; Fernandez-Avellaneda, Pedro; Breazzano, Mark P.; Yannuzzi, Lawrence A.; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY 10022 USA.
   [Fragiotta, Serena; Fernandez-Avellaneda, Pedro; Breazzano, Mark P.; Yannuzzi, Lawrence A.; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA.
   [Fragiotta, Serena; Fernandez-Avellaneda, Pedro; Breazzano, Mark P.; Yannuzzi, Lawrence A.; Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY 10016 USA.
   [Fragiotta, Serena] Sapienza Univ Rome, UOSD Ophthalmol, Dept Medicosurg Sci & Biotechnol, Rome, Italy.
   [Fernandez-Avellaneda, Pedro] Basurto Univ Hosp, Dept Ophthalmol, Bilbao, Spain.
   [Breazzano, Mark P.; Yannuzzi, Lawrence A.] Columbia Univ, Coll Phys & Surg, Harkness Eye Inst, New York, NY USA.
   [Curcio, Christine A.] Univ Alabama Birmingham, Sch Med, Dept Ophthalmol & Visual Sci, Birmingham, AL USA.
C3 Vitreous Retina Macula Consultants of New York; Manhattan Eye Ear &
   Throat Hospital; New York University; Sapienza University Rome; Basurto
   Hospital; Columbia University; University of Alabama System; University
   of Alabama Birmingham
RP Freund, KB (通讯作者)，Vitreous Retina Macula Consultants New York, New York, NY 10022 USA.; Freund, KB (通讯作者)，Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA.; Freund, KB (通讯作者)，NYU, Sch Med, Dept Ophthalmol, New York, NY 10016 USA.
EM kbfnyf@aol.com
RI Fragiotta, Serena/I-5227-2016; Freund, K. Bailey/V-7488-2018
OI Fragiotta, Serena/0000-0002-6214-6270; Breazzano,
   Mark/0000-0002-7093-965X; Freund, K. Bailey/0000-0002-7888-9773; Curcio,
   Christine/0000-0001-9769-1538; Fernandez-Avellaneda,
   Pedro/0000-0003-4668-7496
FU Macula Foundation, Inc., New York, NY
FX information This work was supported by The Macula Foundation, Inc., New
   York, NY.
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NR 52
TC 5
Z9 5
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD MAR
PY 2020
VL 258
IS 3
BP 491
EP 501
DI 10.1007/s00417-019-04565-y
EA DEC 2019
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KN4JG
UT WOS:000504467700001
PM 31879821
DA 2022-11-30
ER

PT J
AU Kugelman, J
   Alonso-Caneiro, D
   Read, SA
   Vincent, SJ
   Collins, MJ
AF Kugelman, Jason
   Alonso-Caneiro, David
   Read, Scott A.
   Vincent, Stephen J.
   Collins, Michael J.
TI Automatic segmentation of OCT retinal boundaries using recurrent neural
   networks and graph search
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; SURFACE SEGMENTATION; LAYER BOUNDARIES;
   EYE GROWTH; IMAGES; THICKNESS; BACKPROPAGATION
AB The manual segmentation of individual retinal layers within optical coherence tomography (OCT) images is a time-consuming task and is prone to errors. The investigation into automatic segmentation methods that are both efficient and accurate has seen a variety of methods proposed. In particular, recent machine learning approaches have focused on the use of convolutional neural networks (CNNs). Traditionally applied to sequential data, recurrent neural networks (RNNs) have recently demonstrated success in the area of image analysis, primarily due to their usefulness to extract temporal features from sequences of images or volumetric data. However, their potential use in OCT retinal layer segmentation has not previously been reported, and their direct application for extracting spatial features from individual 2D images has been limited. This paper proposes the use of a recurrent neural network trained as a patch-based image classifier (retinal boundary classifier) with a graph search (RNN-GS) to segment seven retinal layer boundaries in OCT images from healthy children and three retinal layer boundaries in OCT images from patients with age-related macular degeneration (AMD). The optimal architecture configuration to maximize classification performance is explored. The results demonstrate that a RNN is a viable alternative to a CNN for image classification tasks in the case where the images exhibit a clear sequential structure. Compared to a CNN, the RNN showed a slightly superior average generalization classification accuracy. Secondly, in terms of segmentation, the RNN-GS performed competitively against a previously proposed CNN based method (CNN-GS) with respect to both accuracy and consistency. These findings apply to both normal and AMD data. Overall, the RNN-GS method yielded superior mean absolute errors in terms of the boundary position with an average error of 0.53 pixels (normal) and 1.17 pixels (AMD). The methodology and results described in this paper may assist the future investigation of techniques within the area of OCT retinal segmentation and highlight the potential of RNN methods for OCT image analysis. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
C1 [Kugelman, Jason; Alonso-Caneiro, David; Read, Scott A.; Vincent, Stephen J.; Collins, Michael J.] Queensland Univ Technol, Sch Optometry & Vis Sci, Contact Lens & Visual Opt Lab, Brisbane, Qld, Australia.
C3 Queensland University of Technology (QUT)
RP Alonso-Caneiro, D (通讯作者)，Queensland Univ Technol, Sch Optometry & Vis Sci, Contact Lens & Visual Opt Lab, Brisbane, Qld, Australia.
EM d.alonsocaneiro@qut.edu.au
RI Vincent, Stephen J/H-6548-2019; Collins, Michael/I-9553-2012
OI Vincent, Stephen J/0000-0002-5998-1320; Read, Scott/0000-0002-1595-673X;
   Alonso-Caneiro, David/0000-0002-7754-6592; Collins,
   Michael/0000-0001-5226-5498
FU Rebecca L. Cooper 2018 Project Grant; Telethon - Perth Children's
   Hospital Research Fund
FX Rebecca L. Cooper 2018 Project Grant (DAC); Telethon - Perth Children's
   Hospital Research Fund (DAC).
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   Zhang B., 2016, ARXIV160708725
NR 69
TC 62
Z9 62
U1 2
U2 8
PU Optica Publishing Group
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD NOV 1
PY 2018
VL 9
IS 11
BP 5759
EP 5777
DI 10.1364/BOE.9.005759
PG 19
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
GA GZ2EZ
UT WOS:000449192700044
PM 30460160
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Abdelfattah, NS
   Hariri, AH
   Al-Sheikh, M
   Pitetta, S
   Ebraheem, A
   Wykoff, CC
   Sadda, SR
AF Abdelfattah, Nizar Saleh
   Hariri, Amir H.
   Al-Sheikh, Mayss
   Pitetta, Sean
   Ebraheem, Adel
   Wykoff, Charles C.
   Sadda, Srinivas R.
CA Trex-Amd Study Grp
TI Topographic Correspondence of Macular Atrophy With Choroidal
   Neovascularization in Ranibizumab-treated Eyes of the TREX-AMD Trial
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GROWTH-FACTOR THERAPY; GEOGRAPHIC ATROPHY; VISUAL IMPAIRMENT;
   DEGENERATION; PREVALENCE; PROGRESSION; EXTEND
AB PURPOSE: To quantify the extent of topographic correspondence between baseline (BSL) choroidal neovascularization (CNV) and macular atrophy (MA) at follow-up in eyes with neovascular age-related macular degeneration (NVAMD).
   DESIGN: Post hoc analysis of randomized controlled clinical trial data.
   METHODS: Sixty treatment-naive NVAMD patients from the TREX-AMD trial were followed for 18 months. Regions of month 18 macular atrophy (MA) were graded on fundus autofluorescence (FAF) with guidance of spectral-domain optical coherence tomography (SDOCT). CNV lesions were graded manually on fluorescein angiography (FA) with lesion components including classic and occult CNV delineated. FAF and FA images were registered to quantitate area and location of overlap between CNV and MA. Outcome measures included overlap of month 18 MA to BSL CNV subtype and progression of MA from BSL to month 18.
   RESULTS: Twenty-six eyes had both MA at month 18 and CNV at BSL. A total of 84.6% of eyes showed evidence of MA and CNV overlap. MA appeared by month 18 in regions corresponding to BSL classic CNV in 36.4% of eyes and occult CNV in 40.9%, and in both regions in 22.7%, with more area of MA (AMA) in regions of occult than classic CNV. MA position at BSL corresponded to BSL classic CNV in 76.9% of eyes and occult CNV in 61.5%, and to both regions in 15.4%, with more AMA in regions of occult than classic CNV. Among eyes with MA and CNV at BSL but with no overlap, 50% progressed to involve regions with BS-CNV. Six eyes had no BSL MA but developed MA at month 18 within regions of BSL CNV.
   CONCLUSIONS: In ranibizumab-treated eyes with NVAMD, more MA lesions develop within the region of baseline CNV (type 1, CNV-based MA) than outside (type 2, CNV-independent MA). Baseline-MA also tends to be located within regions of CNV in the pretreatment phase. (C) 2018 Elsevier Inc. All rights reserved.
C1 [Abdelfattah, Nizar Saleh; Hariri, Amir H.; Al-Sheikh, Mayss; Pitetta, Sean; Ebraheem, Adel; Sadda, Srinivas R.] Doheny Eye Inst, Doheny Image Reading Ctr, 1355 San Pablo St, Los Angeles, CA 90033 USA.
   [Abdelfattah, Nizar Saleh; Hariri, Amir H.; Al-Sheikh, Mayss; Ebraheem, Adel; Sadda, Srinivas R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Wykoff, Charles C.] Retina Consultants Houston, Houston, TX USA.
   [Wykoff, Charles C.] Houston Methodist Hosp, Blanton Eye Inst, Houston, TX USA.
   [Wykoff, Charles C.] Weill Cornell Med Coll, Houston, TX USA.
C3 Doheny Eye Institute; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA; The Methodist Hospital
   System; The Methodist Hospital - Houston; Cornell University
RP Abdelfattah, NS (通讯作者)，Doheny Eye Inst, 1355 San Pablo St,Suite 100, Los Angeles, CA 90033 USA.
EM myretina@outlook.com
RI Abdelfattah, Nizar Saleh/H-6908-2019
OI Abdelfattah, Nizar Saleh/0000-0002-9396-3054; Wang,
   Rui/0000-0002-0900-7714
CR Abdelfattah NS, 2017, OPHTHALMOLOGY, V124, P215, DOI 10.1016/j.ophtha.2016.10.002
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NR 29
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD AUG
PY 2018
VL 192
BP 84
EP 90
DI 10.1016/j.ajo.2018.05.008
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GP9HA
UT WOS:000441226900014
PM 29763612
DA 2022-11-30
ER

PT J
AU Moran, R
   Beatty, S
   Stack, J
   O'Halloran, AM
   Feeney, J
   Akuffo, KO
   Peto, T
   Kenny, RA
   Nolan, JM
AF Moran, Rachel
   Beatty, Stephen
   Stack, Jim
   O'Halloran, Aisling M.
   Feeney, Joanne
   Akuffo, Kwadwo O.
   Peto, Tunde
   Kenny, Rose Anne
   Nolan, John M.
TI The Relationship Between Plasma Concentrations of Lutein and Zeaxanthin
   with Self-Reported and Actual Prevalence of AMD in an Irish
   Population-Based Sample
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Lutein; zeaxanthin; awareness; supplements; age-related macular
   degeneration
ID AGE-RELATED MACULOPATHY; PIGMENT OPTICAL-DENSITY; MACULAR DEGENERATION;
   NUTRITIONAL MANIPULATION; PRIMATE RETINAS; SERUM CONCENTRATIONS;
   SUPPLEMENTAL LUTEIN; VISUAL FUNCTION; RISK-FACTORS; EYE DISEASE
AB Purpose: To investigate plasma lutein (L) and zeaxanthin (Z) concentrations with grading-confirmed and self-reported prevalence of age-related macular degeneration (AMD).
   Material and methods: Data collected from a nationally representative prospective cohort study of community-dwelling adults aged 50years and over in the Republic of Ireland. Participants underwent a computer-assisted personal interview and a center-based health assessment. Plasma concentrations of L and total Z (Z and meso-zeaxanthin [MZ]) were measured by high performance liquid chromatography, and retinal photographs were graded using a version of the AMD International Classification and Grading System. Consumption of supplements containing L and/or Z and/or MZ was recorded as supplement use. Four groups were identified: Group 1 (n = 24): AMD-afflicted and correctly aware; Group 2 (n = 264): AMD-afflicted but unaware; Group 3 (n = 41): AMD-free and incorrectly believed that they were afflicted with the condition; Group 4 (n = 4094): AMD-free and correctly self-reported absence of AMD.
   Results: Of 4,423 participants with plasma concentrations of L and Z and gradable retinal photographs, 288 (6.5%) were afflicted with AMD, and 65 (1.5%) self-reported AMD. Controlling for family history and age, the relationship between grading-confirmed AMD and plasma L was positive and significant (p < 0.001). Mean plasma concentrations of L in Group 2 (mean = 0.2162 +/- 0.132 mu mol) and Group 4 (mean = 0.2040 +/- 0.121 mu mol/L) were significantly lower than Group 1 (mean = 0.4691 +/- 0.0.372 mu mol/L) and Group 3 (mean = 0.3176 +/- 0.0.235 mu mol/L). Supplement use was reported by 41.7% and 17.1% of participants in Groups 1 and 3, respectively, but only 2.7% and 1.9% of participants in Groups 2 and 4, respectively.
   Conclusion: A belief that one suffers from AMD, whether justified or not, is associated with supplement use and with higher plasma concentrations of L.
C1 [Moran, Rachel; Beatty, Stephen; Stack, Jim; Akuffo, Kwadwo O.; Nolan, John M.] Waterford Inst Technol, Sch Hlth Sci, Macular Pigment Res Grp, Nutr Res Ctr Ireland, Waterford, Ireland.
   [O'Halloran, Aisling M.; Feeney, Joanne; Kenny, Rose Anne] Trinity Coll Dublin, Dept Med Gerontol, Irish Longitudinal Study Ageing, Dublin, Ireland.
   [Feeney, Joanne] Queens Univ, Sch Med Dent & Biomed Sci, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
   [Peto, Tunde] Moorfields Eye Hosp, NIHR Biomed Res Ctr, London, England.
   [Peto, Tunde] UCL Inst Ophthalmol, London, England.
C3 South East Technological University (SETU); Trinity College Dublin;
   Queens University Belfast; University of London; University College
   London; Moorfields Eye Hospital NHS Foundation Trust; University of
   London; University College London
RP Moran, R (通讯作者)，Waterford Inst Technol, Nutr Res Ctr Ireland, Macular Pigment Res Grp, West Campus, Carriganore, Waterford, Ireland.
EM rmoran@wit.ie
RI Peto, Tunde/G-8812-2018; Akuffo, Kwadwo Owusu/J-2036-2019; Nolan,
   John/N-4921-2014
OI Peto, Tunde/0000-0001-6265-0381; Akuffo, Kwadwo
   Owusu/0000-0001-6683-249X; Nolan, John/0000-0002-5503-7084; Kenny, Rose
   Anne/0000-0002-9336-8124; Feeney, Joanne/0000-0001-9872-2025;
   O'Halloran, Aisling/0000-0001-5498-4453
FU Bayer, Ireland; Waterford Institute of Technology Presidential
   Scholarship; An Roinn Slainte (Irish Department of Health); Atlantic
   Philanthropies; Irish Life plc.; European Research Council (ERC); Centre
   for Ageing Development and Research in Ireland (CARDI); NIHR BMRC at
   Moorfields Eye Hospital NHS Foundation Trust; UCL Institute of
   Ophthalmology, London, UK
FX This work was supported by Bayer, Ireland and Waterford Institute of
   Technology Presidential Scholarship. TILDA is funded by An Roinn Slainte
   (Irish Department of Health), The Atlantic Philanthropies, and Irish
   Life plc. The funders had no role in the study design or in the
   collection, analysis and interpretation of the data or in the writing of
   the report or in the decision to submit the article for publication. JMN
   and KOA were funded by the European Research Council (ERC). JF and AOH
   were funded by the Centre for Ageing Development and Research in Ireland
   (CARDI). TP was funded by the NIHR BMRC at Moorfields Eye Hospital NHS
   Foundation Trust and UCL Institute of Ophthalmology, London, UK.
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NR 54
TC 2
Z9 2
U1 0
U2 5
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PY 2018
VL 43
IS 3
BP 383
EP 390
DI 10.1080/02713683.2017.1403633
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FV2SX
UT WOS:000424419400016
PM 29172786
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Vollrath, M
   Engert, J
   Winter, G
AF Vollrath, Moritz
   Engert, Julia
   Winter, Gerhard
TI Long-term release and stability of pharmaceutical proteins delivered
   from solid lipid implants
SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
LA English
DT Article
DE Lipid implants; Twin-screw extrusion; Sustained release; Protein
   stability; Ranibizumab; Monoclonal antibody
ID IN-VITRO RELEASE; MASS-TRANSPORT MECHANISMS; DRUG-RELEASE;
   POLYETHYLENE-GLYCOL; SUSTAINED-RELEASE; DOSAGE FORMS; MACULAR
   DEGENERATION; SECONDARY STRUCTURES; INTERFERON ALPHA-2A; SYSTEMS
AB Solid lipid implants (SLIs) prepared by twin-screw (tsc) extrusion represent a promising technology platform for the sustained release of pharmaceutical proteins. In this work, we report on two aspects, long-term release and stability of released protein. First, SLIs were produced by tsc-extrusion containing the low melting triglyceride H12 and the high melting triglyceride Dynasan D118. Two different proteins available in a freeze-dried matrix containing hydroxypropyl-beta-cyclodextrine (HP-beta-CD) were incorporated into the lipid matrix: a monoclonal antibody (mAb) from the IgG(1) class and the f(ab)-fragment Ranibizumab (Lucentis (R)). SLIs, composed of 10% protein lyophilizate and both triglycerides, were extruded at 35 degrees C and 40 rpm. Sustained release of both proteins was observed in a sustained manner for approximately 120 days. Protein load per implant was increased by three different approaches resulting in a protein load of 3.00 mg per implant without affecting the release profiles. The incubation medium containing the released protein was collected, concentrated and analyzed including liquid chromatography (SE-HPLC, IEX, HIC), electrophoresis (SDS-PAGE, on-chip gel electrophoresis) and FT-IR spectroscopy. The mAb showed a monomer loss of up to 7% (SE-HPLC) and IEX analysis revealed the formation of 16% acidic subspecies after 18 weeks. FT-IR spectra of mAb indicated the formation of random coil structures towards the end of the release study. Ranibizumab was mainly released in its monomeric form (>95%), and approximately 5% hydrophobic subspecies were formed after 18 weeks of release. FT-IR analysis revealed no changes in secondary structure. The release and stability profiles of both proteins underline the potential of SLIs as a delivery system. SLIs provide a promising platform for applications where really long-term release is needed, for example for intraocular delivery of anti-vascular endothelial growth factor (VEGF) drugs for age related macular degeneration (AMD). (C) 2017 Elsevier B.V. All rights reserved.
C1 [Vollrath, Moritz; Engert, Julia; Winter, Gerhard] Ludwig Maximilians Univ Munchen, Dept Pharm Pharmaceut Technol & Biopharmaceut, Butenandtstr 5-13, D-81377 Munich, Germany.
C3 University of Munich
RP Winter, G (通讯作者)，Ludwig Maximilians Univ Munchen, Dept Pharm Pharmaceut Technol & Biopharmaceut, Butenandtstr 5-13, D-81377 Munich, Germany.
EM gerhard.winter@lrz.uni-muenchen.de
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NR 65
TC 14
Z9 14
U1 2
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0939-6411
EI 1873-3441
J9 EUR J PHARM BIOPHARM
JI Eur. J. Pharm. Biopharm.
PD AUG
PY 2017
VL 117
BP 244
EP 255
DI 10.1016/j.ejpb.2017.04.017
PG 12
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA FA0VJ
UT WOS:000405154400024
PM 28442372
DA 2022-11-30
ER

PT J
AU Campochiaro, PA
   Lauer, AK
   Sohn, EH
   Mir, TA
   Naylor, S
   Anderton, MC
   Kelleher, M
   Harrop, R
   Ellis, S
   Mitrophanous, KA
AF Campochiaro, Peter A.
   Lauer, Andreas K.
   Sohn, Elliott H.
   Mir, Tahreem A.
   Naylor, Stuart
   Anderton, Matthew C.
   Kelleher, Michelle
   Harrop, Richard
   Ellis, Scott
   Mitrophanous, Kyriacos A.
TI Lentiviral Vector Gene Transfer of Endostatin/Angiostatin for Macular
   Degeneration (GEM) Study
SO HUMAN GENE THERAPY
LA English
DT Article
DE age-related macular degeneration (AMD); equine infectious anemia viral
   (EIAV) vector; lentiviral vector; subretinal injection; ocular gene
   therapy; neovascularization
ID EPITHELIUM-DERIVED FACTOR; CHOROIDAL NEOVASCULARIZATION; NERVOUS-SYSTEM;
   THERAPY; ANGIOGENESIS; ENDOSTATIN; INHIBITOR; SAFETY; VEGF; ANGIOSTATIN
AB Neovascular age-related macular degeneration (NVAMD) is a prevalent cause of vision loss. Intraocular injections of VEGF-neutralizing proteins provide benefit, but many patients require frequent injections for a prolonged period. Benefits are often lost over time due to lapses in treatment. New treatments that sustain anti-angiogenic activity are needed. This study tested the safety and expression profile of a lentiviral Equine Infectious Anemia Virus (EIAV) vector expressing endostatin and angiostatin (Retino-Stat (R)). Patients with advanced NVAMD were enrolled at three centers in the United States, and the study eye received a subretinal injection of 2.4 x 10(4) (n = 3), 2.4 x 10(5) (n = 3), or 8.0 x 10(5) transduction units (TU; n = 15). Each of the doses was well-tolerated with no dose-limiting toxicities. There was little or no ocular inflammation. There was one procedure-related serious adverse event (AE), a macular hole, which was managed without difficulty and resolved. There was a vector dose-related increase in aqueous humor levels of endostatin and angiostatin with high reproducibility among subjects within cohorts. Mean levels of endostatin and angiostatin peaked between 12 and 24 weeks after injection of 2.4 x 10(5) TU or 8.0 x 10(5) TU at 57-81 ng/mL for endostatin and 15-27 ng/mL for angiostatin, and remained stable through the last measurement at week 48. Long-term follow-up demonstrated expression was maintained at last measurement (2.5 years in eight subjects and >4 years in two subjects). Despite an apparent reduction in fluorescein angiographic leakage that broadly correlated with the expression levels in the majority of patients, only one subject showed convincing evidence of anti-permeability activity in these late-stage patients. There was no significant change in mean lesion size in subjects injected with 8.0 x 10(5) TU. These data demonstrate that EIAV vectors provide a safe platform with robust and sustained transgene expression for ocular gene therapy.
C1 [Campochiaro, Peter A.; Mir, Tahreem A.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
   [Lauer, Andreas K.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
   [Sohn, Elliott H.] Univ Iowa Hosp & Clin, Dept Ophthalmol, Iowa City, IA 52242 USA.
   [Naylor, Stuart; Anderton, Matthew C.; Kelleher, Michelle; Harrop, Richard; Ellis, Scott; Mitrophanous, Kyriacos A.] Oxford BioMed UK Ltd, Oxford, England.
C3 Johns Hopkins University; Johns Hopkins Medicine; Oregon Health &
   Science University; University of Iowa; Oxford Biomedica (UK) Ltd
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ, Sch Med, Maumenee 815,600 N Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhmi.edu
OI Sohn, Elliott/0000-0002-3778-9362
FU Oxford BioMedica (UK) Ltd.
FX The study was funded by Oxford BioMedica (UK) Ltd.
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NR 38
TC 105
Z9 113
U1 1
U2 10
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
EI 1557-7422
J9 HUM GENE THER
JI Hum. Gene Ther.
PD JAN
PY 2017
VL 28
IS 1
BP 99
EP 111
DI 10.1089/hum.2016.117
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA EI9HF
UT WOS:000392817800004
PM 27710144
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Roehlecke, C
   Valtink, M
   Frenzel, A
   Goetze, D
   Knels, L
   Morawietz, H
   Funk, RHW
AF Roehlecke, Cora
   Valtink, Monika
   Frenzel, Annika
   Goetze, Doris
   Knels, Lilla
   Morawietz, Henning
   Funk, Richard H. W.
TI Stress responses of human retinal pigment epithelial cells to glyoxal
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Glyoxal; Advanced glycation end products (AGEs);
   N-epsilon-carboxymethyllysine (CML); Oxidative stress; Retinal pigment
   epithelium; VEGF
ID GLYCATION END-PRODUCTS; GROWTH-FACTOR EXPRESSION; LATE DIABETIC
   COMPLICATIONS; MACULAR DEGENERATION; INTRACELLULAR PH; OXIDATIVE STRESS;
   HEME OXYGENASE-1; IN-VITRO; FLOW-CYTOMETRY; RECEPTOR RAGE
AB Intracellular formation of advanced glycation end products (AGEs) is a crucial pathological process in retinal diseases such as age-related macular degeneration (AMD) or diabetic retinopathy (DR). Glyoxal is a physiological metabolite produced during formation of AGEs and has also been shown to derive from photodegraded bisretinoid fluorophores in aging retinal pigment epithelial (RPE) cells.
   Flow cytometry was combined with either: 1) immunocytochemical staining to detect glyoxal induced formation of N-epsilon-carboxymethyllysine (CML)-modifications of intracellular proteins (AGEs) and changes in the production of stress response proteins; or 2) vital staining to determine apoptosis rates (annexin V binding), formation of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and changes in intracellular pH upon treatment of cells with glyoxal. The percentage of apoptotic cells was further quantified by flow cytometry after staining of fixed cells with propidium iodide to determine cells with a subdiploid (fragmented) DNA content. Apoptosis related activation of caspase 3 was determined by Western blotting. Glyoxal induced changes in VEGF-A(165a) mRNA expression and protein production were determined by real-time PCR and by flow cytometry after immunocytochemical staining.
   Increasing glyoxal concentrations resulted in enhanced formation of AGEs, such as CML modifications of proteins. This was associated with elevated levels of intracellular reactive oxygen species, a depolarized MMP, and a decreased intracellular pH, resulting in an increased number of apoptotic cells. Apoptosis related caspase 3 activation increased in a dose dependent manner after glyoxal incubation. In consequence, the cells activated compensatory mechanisms and increased the levels of the anti-oxidative and stress-related proteins heme oxygenase-1, osteopontin, heat shock protein 27, copper/zinc superoxide dismutase, manganese superoxide dismutase, and cathepsin D. Furthermore, VEGF-A(165a) mRNA expression and VEGF-A protein production were significantly increased after incubation with glyoxal in ARPE-19 cells.
   The glyoxal-induced oxidative stress and apoptosis in ARPE-19 cells may provide a suitable in vitro model for studying RPE cellular reactions to AGEs that occur in AMD or in DR.
C1 [Roehlecke, Cora; Valtink, Monika; Goetze, Doris; Knels, Lilla; Funk, Richard H. W.] Tech Univ Dresden, Fac Med Carl Gustav Carus, Inst Anat, Fetscherstr 74, D-01307 Dresden, Germany.
   [Frenzel, Annika; Morawietz, Henning] Tech Univ Dresden, Fac Med Carl Gustav Carus, Div Vasc Endothelium & Microcirculat, Med Clin 3,Div Vasc Endothelium & Microcirculat, Fetscherstr 74, D-01307 Dresden, Germany.
   [Morawietz, Henning; Funk, Richard H. W.] Tech Univ Dresden, CRTD DFG Ctr Regenerat Therapies Dresden Cluster, Fetscherstr 105, D-01307 Dresden, Germany.
C3 Technische Universitat Dresden; Technische Universitat Dresden;
   Technische Universitat Dresden
RP Valtink, M (通讯作者)，Tech Univ Dresden, Fac Med Carl Gustav Carus, Inst Anat, Fetscherstr 74, D-01307 Dresden, Germany.
EM monika.valtink@tu-dresden.de
RI Valtink, Monika/I-1507-2013
OI Valtink, Monika/0000-0003-3205-1876
FU Deutsche Forschungsgemeinschaft (DFG) Excellence Initiative by the
   German Federal Government [MO1695/4-1, MO1695/5-1]; Deutsche
   Forschungsgemeinschaft (DFG) Excellence Initiative by the German State
   Government [MO1695/4-1, MO1695/5-1]
FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG)
   (funding of the Excellence Initiative by the German Federal and State
   Governments, Institutional Strategy, measure "support the best" to HM
   and RHWF, MO1695/4-1 and MO1695/5-1 to HM).
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NR 65
TC 7
Z9 7
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD DEC
PY 2016
VL 254
IS 12
BP 2361
EP 2372
DI 10.1007/s00417-016-3463-2
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EC6OT
UT WOS:000388256500009
PM 27520463
DA 2022-11-30
ER

PT J
AU de Pedro-Cuesta, J
   Rabano, A
   Martinez-Martin, P
   Ruiz-Tovar, M
   Alcalde-Cabero, E
   Almazan-Isla, J
   Avellanal, F
   Calero, M
AF de Pedro-Cuesta, Jesus
   Rabano, Alberto
   Martinez-Martin, Pablo
   Ruiz-Tovar, Maria
   Alcalde-Cabero, Enrique
   Almazan-Isla, Javier
   Avellanal, Fuencisla
   Calero, Miguel
TI Comparative Incidence of Conformational, Neurodegenerative Disorders
SO PLOS ONE
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; CREUTZFELDT-JAKOB-DISEASE; 3 ELDERLY
   POPULATIONS; PARKINSONS-DISEASE; ALZHEIMER-DISEASE; MACULAR
   DEGENERATION; HUNTINGTONS-DISEASE; ESSENTIAL TREMOR; CENTRAL SPAIN; LEWY
   BODIES
AB Background
   The purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs).
   Methods
   We identified 2563 reports on the incidence of eight conditions representing sporadic, acquired and genetic, protein-associated, i.e., conformational, NDD groups and age-related macular degeneration (AMD). We selected 245 papers for full-text examination and application of quality criteria. Additionally, data-collection was completed with detailed information from British, Swedish, and Spanish registries on Creutzfeldt-Jakob disease (CJD) forms, amyotrophic lateral sclerosis (ALS), and sporadic rapidly progressing neurodegenerative dementia (sRPNDd). For each condition, age-specific incidence curves, age-adjusted figures, and reported or calculated median survival were plotted and examined.
   Findings
   Based on 51 valid reported and seven new incidence data sets, nine out of eleven conditions shared specific features. Age-adjusted incidence per million person-years increased from <= 1.5 for sRPNDd, different CJD forms and Huntington's disease (HD), to 1589 and 2589 for AMD and Alzheimer's disease (AD) respectively. Age-specific profiles varied from (a) symmetrical, inverted V-shaped curves for low incidences to (b) those increasing with age for late-life sporadic CNDDs and for sRPNDd, with (c) a suggested, intermediate, non-symmetrical inverted V-shape for fronto-temporal dementia and Parkinson's disease. Frequently, peak age-specific incidences from 20-24 to >= 90 years increased with age at onset and survival. Distinct patterns were seen: for HD, with a low incidence, levelling off at middle age, and long median survival, 20 years; and for sRPNDd which displayed the lowest incidence, increasing with age, and a short median disease duration.
   Interpretation
   These results call for a unified population view of NDDs, with an age-at-onset-related pattern for acquired and sporadic CNDDs. The pattern linking age at onset to incidence magnitude and survival might be explained by differential pathophysiological mechanisms associated with specific misfolded protein deposits.
C1 [de Pedro-Cuesta, Jesus; Martinez-Martin, Pablo; Ruiz-Tovar, Maria; Alcalde-Cabero, Enrique; Almazan-Isla, Javier; Avellanal, Fuencisla] Natl Inst Hlth Carlos III, CNE, Dept Appl Epidemiol, Madrid, Spain.
   [de Pedro-Cuesta, Jesus; Martinez-Martin, Pablo; Ruiz-Tovar, Maria; Alcalde-Cabero, Enrique; Almazan-Isla, Javier; Avellanal, Fuencisla] Natl Inst Hlth Carlos III, Consortium Biomed Res Neurodegenerat Dis CIBERNED, Madrid, Spain.
   [Rabano, Alberto; Calero, Miguel] Reina Sofia Fdn, Alzheimers Dis Ctr, Madrid, Spain.
   [Calero, Miguel] Natl Inst Hlth Carlos III, CIBERNED, Majadahonda, Spain.
C3 Instituto de Salud Carlos III; CIBERNED; Instituto de Salud Carlos III;
   CIBERNED; Instituto de Salud Carlos III
RP de Pedro-Cuesta, J (通讯作者)，Natl Inst Hlth Carlos III, CNE, Dept Appl Epidemiol, Madrid, Spain.
EM jpedro@isciii.es
RI Calero, Miguel/H-5691-2015; Ruiz-Tovar, Maria/F-4631-2016;
   Martinez-Martin, Pablo/N-9909-2019
OI Calero, Miguel/0000-0001-5366-3324; Ruiz-Tovar,
   Maria/0000-0002-5102-4905; Martinez-Martin, Pablo/0000-0003-0837-5280;
   Almazan-Isla, Javier/0000-0001-8723-339X
FU Consortium for Biomedical Research in Neurodegenerative Diseases (Centro
   de Investigacion Biomedica en Red sobre Enfermedades
   Neurodegenerativas/CIBERNED); ISCIII Field Epidemiology Program; EU
   Joint Program - Neurodegenerative Disease Research (JPND - DEMTEST) [FIS
   PI11/03021]
FX Funding was received from the Consortium for Biomedical Research in
   Neurodegenerative Diseases (Centro de Investigacion Biomedica en Red
   sobre Enfermedades Neurodegenerativas/CIBERNED) as part of the 2014-2015
   annual Budgets of the CIBERNED 509-group. Mr Alcalde received support
   from the ISCIII Field Epidemiology Program during 2014 and 2015. The
   study was partially supported by grant from the EU Joint Program -
   Neurodegenerative Disease Research (JPND - DEMTEST (Spanish FIS
   PI11/03021)). The funders had no role in study design, data collection
   and analysis, decision to publish, or preparation of the manuscript.
   Authors other than EAC received no specific funding for this work.
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NR 51
TC 14
Z9 14
U1 0
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 3
PY 2015
VL 10
IS 9
AR e0137342
DI 10.1371/journal.pone.0137342
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CQ5AJ
UT WOS:000360615400050
PM 26335347
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Han, DM
   Yao, Y
   Sun, Y
   Gong, YY
   Wu, XW
AF Han, Dongmei
   Yao, Yuan
   Sun, Yong
   Gong, Yuanyuan
   Wu, Xingwei
TI Effect of charred Radix et Rhizoma Rhei in a laser-induced choroidal
   neovascularization murine model
SO MOLECULAR MEDICINE REPORTS
LA English
DT Article
DE charred Radix et Rhizoma Rhei; choroidal neovascularization; traditional
   Chinese medicine; age-associated macular degeneration; interleukin-10
ID MACULAR DEGENERATION; ANGELICA-SINENSIS; INTRAVITREAL TRIAMCINOLONE;
   ANTIINFLAMMATORY ACTIVITY; PHOTODYNAMIC THERAPY; PANAX-NOTOGINSENG;
   PORIA-COCOS; IN-VITRO; EXTRACT; EXPRESSION
AB A pharmaceutical composition (patent no. WO2012079419) exhibited favorable outcomes in a clinical trial of wet age-related macular degeneration. The aims of the present study were to explore the effects of one composition component, charred Radix et Rhizoma Rhei (CRRR), in a laser-induced choroidal neovascularization (CNV) murine model. A total of 30 eight-week-old C57BL/6 mice were subjected to diode laser treatment, and CNV was induced by rupturing the Bruch's membrane. The mice were then randomly divided into two groups: the CRRR-treated group that was administered CRRR water extract (concentration, 0.6 g/100 ml; dose, 1 ml/0.1 kg twice a day for 21 days); and the control group that was treated with saline (dose, 1 ml/0.1 kg twice a day for 21 days). The retinal tissue was subjected to quantitative polymerase chain reaction (qPCR) and western blot analysis to determine the expression levels of interleukin-10 (IL-10) and vascular epithelial growth factor (VEGF) at day seven following laser treatment. At weeks 2 and 3 after laser treatment, fundus fluorescein angiography was performed and graded to assess the severity of lesion leakage. Retinal flat mounts were prepared for three-dimensional confocal microscopy at day 22 after laser treatment. At days 14 and 21 after laser treatment, no statistically significant differences were observed between the clinically relevant lesions of the CRRR-treated and control mice. CNV volumes were not found to be significantly different between the CRRR-treated and control mice. The expression levels of IL-10 were significantly increased in the CRRR-treated mice (P<0.05). However, no statistically significant differences were observed between the VEGF expression levels of the CRRR-treated and control mice. In conclusion, CRRR did not appear to significantly inhibit CNV in this murine model. The function of CRRR in the pharmaceutical composition may be due to the effects of IL-10 and a synergistic effect with other components of the composition. However, further investigation is required.
C1 [Han, Dongmei; Yao, Yuan; Sun, Yong; Gong, Yuanyuan; Wu, Xingwei] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Ophthalmol, Shanghai 200080, Peoples R China.
C3 Shanghai Jiao Tong University
RP Wu, XW (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Ophthalmol, 85 Wujin Rd, Shanghai 200080, Peoples R China.
EM wuxingwei2014@126.com
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NR 50
TC 5
Z9 5
U1 0
U2 13
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1791-2997
EI 1791-3004
J9 MOL MED REP
JI Mol. Med. Rep.
PD APR
PY 2015
VL 11
IS 4
BP 2896
EP 2902
DI 10.3892/mmr.2014.3046
PG 7
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA CE3FG
UT WOS:000351711100074
PM 25482457
OA Bronze
DA 2022-11-30
ER

PT J
AU Klein, R
   Lee, KE
   Gangnon, RE
   Klein, BEK
AF Klein, Ronald
   Lee, Kristine E.
   Gangnon, Ronald E.
   Klein, Barbara E. K.
TI Relation of Smoking, Drinking, and Physical Activity to Changes in
   Vision over a 20-Year Period The Beaver Dam Eye Study
SO OPHTHALMOLOGY
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; 15-YEAR CUMULATIVE INCIDENCE; REPORTED VISUAL
   IMPAIRMENT; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION;
   ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; RISK-FACTORS; LENS OPACITIES;
   ASSOCIATION
AB Objective: To describe the relationships of lifestyle characteristics to changes in vision and incidence of visual impairment (VI) over a 20-year period in the Beaver Dam Eye Study (BDES).
   Design: Longitudinal, population-based cohort study.
   Participants: A cohort of 4926 persons aged 43 to 86 years participated in the baseline examinations in 1988-1990, and 3721, 2962, 2375, and 1913 persons participated in follow-up examinations in 1993-1995, 1998-2000, 2003-2005, and 2008-2010, respectively.
   Methods: Best-corrected visual acuity (BCVA) measured by a modified Early Treatment Diabetic Retinopathy Study protocol.
   Main Outcome Measures: Change in number of letters read correctly and incidence of VI based on BCVA in the better eye assessed at each examination over a 20-year period.
   Results: The 20-year cumulative incidence of VI was 5.4%. There was a mean loss of 1.6 letters between examinations, with a 20-year loss of 6.6 letters. While adjusting for age, income, and age-related macular degeneration (AMD) severity, being a current or past smoker was related to a greater change in the numbers of letters lost. Persons who had not consumed alcoholic beverages over the past year and sedentary persons had higher odds of incident VI than persons who drank occasionally or who were physically active. For example, in women with early AMD and annual household income less than $ 10 000, the estimated 20-year cumulative incidence of VI in those who drank occasionally and were physically active was 5.9% compared with 25.8% in women who had not consumed alcoholic beverages over the past year and were sedentary.
   Conclusions: Three modifiable behaviorsdsmoking, drinking alcohol, and physical activity-were associated with changes in vision. Further evidence that changes in these behaviors will result in less loss of vision is needed because of the expected increase in the burden of VI due to the aging of the population. (C) 2014 by the American Academy of Ophthalmology.
C1 [Klein, Ronald; Lee, Kristine E.; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA.
   [Gangnon, Ronald E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53726 USA.
   [Gangnon, Ronald E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53726 USA.
C3 University of Wisconsin System; University of Wisconsin Madison;
   University of Wisconsin System; University of Wisconsin Madison;
   University of Wisconsin System; University of Wisconsin Madison
RP Klein, R (通讯作者)，Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, 610 N Walnut St,4th Floor WARF, Madison, WI 53726 USA.
EM kleinr@epi.ophth.wisc.edu
OI Gangnon, Ronald/0000-0003-2587-6714
FU National Institutes of Health [EY06594]; NATIONAL EYE INSTITUTE
   [U10EY006594] Funding Source: NIH RePORTER
FX The National Institutes of Health Grant EY06594 (R.K. and B.E.K.K.)
   provided funding for the entire study, including collection and analyses
   of data; further support for data analyses was provided by Research to
   Prevent Blindness (R.K. and B.E.K.K., Senior Scientific Investigator
   Awards), New York, New York. R. K. had full access to all the data in
   the study and takes responsibility for the integrity of the data and the
   accuracy of the data analysis. The funding organizations had no role in
   the design or conduct of this research.
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NR 33
TC 40
Z9 41
U1 0
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUN
PY 2014
VL 121
IS 6
BP 1220
EP 1228
DI 10.1016/j.ophtha.2014.01.003
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AJ0KG
UT WOS:000337339100014
PM 24594095
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zhang, ZX
   Wang, YS
   Shi, YY
   Hou, HY
   Zhang, C
   Cai, Y
   Dou, GR
   Yao, LB
   Li, FY
AF Zhang, Zhao-Xia
   Wang, Yu-Sheng
   Shi, Yuan-Yuan
   Hou, Hui-Yuan
   Zhang, Chu
   Cai, Yan
   Dou, Guo-Rui
   Yao, Li-Bo
   Li, Fu-Yang
TI Hypoxia Specific SDF-1 Expression by Retinal Pigment Epithelium
   Initiates Bone Marrow-derived Cells to Participate in Choroidal
   Neovascularization in a Laser-induced Mouse Model
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Choroidal neovascularization; Bone marrow-derived cells; Stromal
   cell-derived factor-1; Hypoxia-inducible factor-1a; Hypoxia
ID ENDOTHELIAL PROGENITOR CELLS; SYSTEMIC VASCULAR-DISEASE; CHEMOKINE
   RECEPTOR CXCR4; HEMATOPOIETIC STEM-CELLS; FACTOR-I; GROWTH-FACTOR;
   MACULAR DEGENERATION; CD34(+) CELLS; INDUCIBLE FACTOR-1-ALPHA;
   ERYTHROPOIETIN GENE
AB Purpose: Choroidal neovascularization (CNV) is a major cause of vision loss in patients with age-related macular degeneration (AMD). Stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) plays a critical role in homing of bone marrow-derived cells (BMCs) to choroidal neovascularization (CNV). In this study, we investigated the contribution of hypoxia specific HIF-1 alpha-induced SDF-1 expression in retinal pigment epithelium (RPE) cells and the potential role of SDF-1 in CNV formation.
   Materials and Methods: Green fluorescent protein (GFP) chimeric mice were developed by transplanting bone marrow cells of gfp(+/+) transgenic mice to sublethally irradiated C57BL/6J mice. CNV was induced by laser photocoagulation. Ocular tissue was processed for immunofluorescence to detect HIF-1 alpha and SDF-1 expression, and cell surface markers such as CXCR4, CD34 and CD31 and so on during CNV formation. In vitro, adult human RPE (hRPE) cells were cultured under conditions of chemical hypoxia using CoCl 2 administration. And RNAi technique was used to knock down HIF-1 alpha gene to observe the expression of HIF-1 alpha and SDF-1 in hRPE cells.
   Results: BMCs trafficked around laser lesion adjacent to RPE layer 4 h after laser photocoagulation, where SDF-1 expression was relatively higher. With increasing expression of SDF-1, more BMCs were infiltrated into laser lesion to participate in CNV, and both reached peak at 3 d (p < 0.05). About 81% BMCs involved in CNV were CXCR4(+). Many of them acquired the surface marker of endothelial precursor cells (CD34(+)) and endothelial cells (CD31(+)). The constituent ratio of CD34(+) and CD31(+) BMCs increased with SDF-1 expression. In vitro, we proved that hypoxia specific-HIF-1 alpha influenced SDF-1 expression in hRPE cells.
   Conclusions: These findings suggested that hypoxia-induced SDF-1 expression in RPE might be a critical initiator for recruitment of BMCs in CNV. SDF-1 might be another important factor in BMCs' differentiation into endothelial cells to participate in the CNV.
C1 [Zhang, Zhao-Xia; Wang, Yu-Sheng; Shi, Yuan-Yuan; Hou, Hui-Yuan; Zhang, Chu; Cai, Yan; Dou, Guo-Rui] Fourth Mil Med Univ, Dept Ophthalmol, Xijing Hosp, Xian 710032, Shaanxi, Peoples R China.
   [Yao, Li-Bo; Li, Fu-Yang] Fourth Mil Med Univ, Dept Biochem & Mol Biol, Xian 710032, Shaanxi, Peoples R China.
C3 Air Force Military Medical University; Air Force Military Medical
   University
RP Wang, YS (通讯作者)，Fourth Mil Med Univ, Dept Ophthalmol, Xijing Hosp, Xian 710032, Shaanxi, Peoples R China.
EM wangys@fmmu.edu.cn; fuyangli@fmmu.edu.cn
RI Hou, Huiyuan/AAI-3718-2020
OI Hou, Huiyuan/0000-0003-0082-8353
FU National Basic Research Program of China (973 Program) [2011CB510200];
   National Natural Science Foundation of China [30371516, 30672291,
   81070748]; Alexander Von Humboldt Foundation in Germany [V8151/02085]
FX This study was funded by: the National Basic Research Program of China
   (973 Program/2011CB510200), the National Natural Science Foundation of
   China (No. 30371516, No. 30672291, No. 81070748), and the Alexander Von
   Humboldt Foundation in Germany (to Y.S.W., V8151/02085)
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NR 67
TC 31
Z9 35
U1 1
U2 15
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0271-3683
J9 CURR EYE RES
JI Curr. Eye Res.
PD SEP
PY 2011
VL 36
IS 9
BP 838
EP 849
DI 10.3109/02713683.2011.593107
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 808WA
UT WOS:000294011300010
PM 21851170
DA 2022-11-30
ER

PT J
AU Bhosale, P
   Zhao, DY
   Bernstein, PS
AF Bhosale, Prakash
   Zhao, Da You
   Bernstein, Paul S.
TI HPLC measurement of ocular carotenoid levels in human donor eyes in the
   lutein supplementation era
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MACULAR PIGMENT; RAMAN MEASUREMENT; ZEAXANTHIN; AUTOFLUORESCENCE;
   IDENTIFICATION; DENSITY; TISSUES; RETINA; PLASMA; SERUM
AB PURPOSE. A substantial proportion of the population at risk for visual loss from age-related macular degeneration consumes supplements containing high doses of lutein, but clinical studies to date have shown only modest and variable increases in macular carotenoid pigments in response to supplementation. To determine whether lutein supplementation can indeed alter ocular carotenoid levels, the authors chemically measured levels of lutein, zeaxanthin, and their metabolites in the macula, peripheral retina, and lens of 228 eyes from 147 human donors and correlated these results with retrospective supplement histories from families of selected members of the study population.
   METHODS. Lenses and circular punches of macula ( 4-mm diameter) and equatorial peripheral retina ( 8-mm diameter) were dissected from donor eyes free of ocular disease procured from the local eye bank. The amounts of lutein, zeaxanthin, mesozeaxanthin, and 3'-oxolutein were determined by HPLC with photodiode array and mass spectral detection.
   RESULTS. Eighteen percent of eyes from donors age 48 and older had unusually high levels ( 66.3 +/- 15.1 ng) of macular carotenoids that were three times the rest of the older population's mean level ( 23.0 + 12.1 ng; P < 0.001). Carotenoid levels in these outliers were also unusually high in the lens and in the peripheral retina. Similar outliers were not present in donors younger than 48. Most of these outliers regularly consumed high-dose lutein supplements before death. Lutein supplementation was uncommon in older donors whose macular carotenoids were in the normal range.
   CONCLUSIONS. The presence of unusually high levels of macular carotenoids in older donors who were regularly consuming high-dose lutein supplements supports the hypothesis that long-term lutein supplementation can raise levels of macular pigment. Elevated carotenoid levels in the peripheral retina and lens in these same donors could have important implications for understanding why some clinical methods of macular pigment measurement have had difficulty detecting robust and consistent responses in carotenoid supplementation trials.
C1 Univ Utah, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Sch Med, Salt Lake City, UT 84132 USA.
C3 Utah System of Higher Education; University of Utah
RP Bernstein, PS (通讯作者)，Univ Utah, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Sch Med, 65 Med Dr, Salt Lake City, UT 84132 USA.
EM paul.bernstein@hsc.utah.edu
FU NATIONAL EYE INSTITUTE [R29EY011600, R01EY011600] Funding Source: NIH
   RePORTER; NEI NIH HHS [EY-11600] Funding Source: Medline
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NR 43
TC 44
Z9 45
U1 0
U2 8
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2007
VL 48
IS 2
BP 543
EP 549
DI 10.1167/iovs.06-0558
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 129KV
UT WOS:000243729300011
PM 17251448
DA 2022-11-30
ER

PT J
AU Chu-Tan, JA
   Cioanca, AV
   Feng, ZP
   Wooff, Y
   Schumann, U
   Aggio-Bruce, R
   Patel, H
   Rutar, M
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   Panov, K
   Provis, J
   Natoli, R
AF Chu-Tan, Joshua A.
   Cioanca, Adrian V.
   Feng, Zhi-Ping
   Wooff, Yvette
   Schumann, Ulrike
   Aggio-Bruce, Riemke
   Patel, Hardip
   Rutar, Matt
   Hannan, Katherine
   Panov, Konstantin
   Provis, Jan
   Natoli, Riccardo
TI Functional microRNA targetome undergoes degeneration-induced shift in
   the retina
SO MOLECULAR NEURODEGENERATION
LA English
DT Article
DE Retina; microRNA; mRNA; Retinal degeneration; Argonaute; HITS-CLIP;
   Transcriptome; Inflammation
ID FACTOR-H POLYMORPHISM; HITS-CLIP; MACULAR DEGENERATION; PROTEIN
   INTERACTIONS; RNA INTERFERENCE; EXPRESSION; IDENTIFICATION;
   INFLAMMATION; DROSOPHILA; MIRNAS
AB Background MicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases including age-related macular degeneration (AMD), acting as post-transcriptional gene suppressors through their association with argonaute 2 (AGO2) - a key member of the RNA Induced Silencing Complex (RISC). Identifying the retinal miRNA/mRNA interactions in health and disease will provide important insight into the key pathways miRNA regulate in disease pathogenesis and may lead to potential therapeutic targets to mediate retinal degeneration. Methods To identify the active miRnome targetome interactions in the healthy and degenerating retina, AGO2 HITS-CLIP was performed using a rodent model of photoreceptor degeneration. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data was performed to identify the cellular location of AGO2 and key members of the microRNA targetome in the retina. AGO2 findings were verified by in situ hybridization (RNA) and immunohistochemistry (protein). Results Analysis revealed a similar miRnome between healthy and damaged retinas, however, a shift in the active targetome was observed with an enrichment of miRNA involvement in inflammatory pathways. This shift was further demonstrated by a change in the seed binding regions of miR-124-3p, the most abundant retinal AGO2-bound miRNA, and has known roles in regulating retinal inflammation. Additionally, photoreceptor cluster miR-183/96/182 were all among the most highly abundant miRNA bound to AGO2. Following damage, AGO2 expression was localized to the inner retinal layers and more in the OLM than in healthy retinas, indicating a locational miRNA response to retinal damage. Conclusions This study provides important insight into the alteration of miRNA regulatory activity that occurs as a response to retinal degeneration and explores the miRNA-mRNA targetome as a consequence of retinal degenerations. Further characterisation of these miRNA/mRNA interactions in the context of the degenerating retina may provide an important insight into the active role these miRNA may play in diseases such as AMD.
C1 [Chu-Tan, Joshua A.; Cioanca, Adrian V.; Wooff, Yvette; Schumann, Ulrike; Aggio-Bruce, Riemke; Provis, Jan; Natoli, Riccardo] Australian Natl Univ, Coll Hlth & Med, John Curtin Sch Med Res, Eccles Inst Neurosci, Canberra, ACT 2601, Australia.
   [Chu-Tan, Joshua A.; Wooff, Yvette; Aggio-Bruce, Riemke; Provis, Jan; Natoli, Riccardo] Australian Natl Univ, Coll Hlth & Med, Sch Med, Canberra, ACT 2601, Australia.
   [Feng, Zhi-Ping; Patel, Hardip] Australian Natl Univ, ANU Bioinformat Consultancy, John Curtin Sch Med Res, Coll Hlth & Med, Canberra, ACT 2601, Australia.
   [Rutar, Matt] Univ Melbourne, Sch Biomed Sci, Parkville, Vic 3010, Australia.
   [Rutar, Matt] Univ Canberra, Fac Sci & Technol, Bruce, ACT 2617, Australia.
   [Hannan, Katherine] Australian Natl Univ, John Curtin Sch Med Res, Coll Hlth & Med, ACRF Dept Canc Biol & Therapeut, Canberra, ACT 2601, Australia.
   [Panov, Konstantin] Queens Univ Belfast, Sch Biol Sci, Belfast BT9 5DL, Antrim, North Ireland.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University; Australian National University; John
   Curtin School of Medical Research; University of Melbourne; University
   of Canberra; Australian National University; John Curtin School of
   Medical Research; Queens University Belfast
RP Natoli, R (通讯作者)，Australian Natl Univ, Coll Hlth & Med, John Curtin Sch Med Res, Eccles Inst Neurosci, Canberra, ACT 2601, Australia.; Natoli, R (通讯作者)，Australian Natl Univ, Coll Hlth & Med, Sch Med, Canberra, ACT 2601, Australia.
EM riccardo.natoli@anu.edu.au
OI Rutar, Matthew/0000-0002-8893-5120; Natoli, Riccardo/0000-0002-9350-0439
FU National Health and Medical Research Council of Australia, Retina
   Australia [NHMRC: 1127705, NHMRC: 202239]; The Gordon and Gretel Bootes
   Foundation; ANU Translational Fellowship; Retina Australia
FX This work would not have been possible without the support of the
   National Health and Medical Research Council of Australia (NHMRC:
   1127705, NHMRC: 202239), Retina Australia, The Gordon and Gretel Bootes
   Foundation and The ANU Translational Fellowship.
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NR 98
TC 2
Z9 2
U1 1
U2 5
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD AUG 31
PY 2021
VL 16
IS 1
AR 60
DI 10.1186/s13024-021-00478-9
PG 21
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA UM3XP
UT WOS:000693267000001
PM 34465369
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Bikbov, MM
   Kazakbaeva, GM
   Zainullin, RM
   Gilmanshin, TR
   Nuriev, IF
   Zaynetdinov, AF
   Yakupova, DF
   Uzianbaeva, YV
   Panda-Jonas, S
   Mukhamadieva, SR
   Khikmatullin, RI
   Aminev, SK
   Arslangareeva, II
   Jonas, JB
AF Bikbov, Mukharram M.
   Kazakbaeva, Gyulli M.
   Zainullin, Rinat M.
   Gilmanshin, Timur R.
   Nuriev, Ildar F.
   Zaynetdinov, Artur F.
   Yakupova, Dilya F.
   Uzianbaeva, Yulia, V
   Panda-Jonas, Songhomitra
   Mukhamadieva, Svetlana R.
   Khikmatullin, Renat, I
   Aminev, Said K.
   Arslangareeva, Inga I.
   Jonas, Jost B.
TI Prevalence and causes of vision impairment and blindness in the Russian
   ural eye and medical study
SO SCIENTIFIC REPORTS
LA English
DT Article
ID GLOBAL PREVALENCE; VISUAL IMPAIRMENT; TEMPORAL TRENDS; CLASSIFICATION;
   POPULATION; DISTANCE
AB To assess prevalence of mild vision impairment (MVI; best corrected visual acuity (BCVA) <6/12 to 6/18 in the better eye), moderate-to-severe vision impairment (MSVI; BCVA <6/18 but >= 3/60) and blindness (BCVA < 3/60) in a local population in Russia, we conducted the population-based Ural Eye and Medical Study. Out of 7,328 eligible individuals aged 40 + years, 5,899 (80.5%) individuals participated. MVI was present in 184 (3.1%; 95% confidence interval (CI) 2.7, 3.6) individuals, MSVI in 182 (3.1%; 95% CI 2.7, 3.5) individuals, and 11 individuals (0.19%; 95% CI 0.008, 0.30) were blind. Causes for MSVI were cataract (n =109; 59.9%), late stage of age-related macular degeneration (n =14; 7.7%; geographic atrophy and neovascular AMD in 7 (3.8%) individuals) each), myopic maculopathy (n =11; 6.0%), glaucoma (n =9; 4.9%), non-glaucomatous optic nerve damage (n =5; 2.7%), and diabetic retinopathy (n = 4; 2.2%). Causes for blindness were cataract (n = 3; 27.3%), myopic maculopathy (n = 2; 18.2%), retinal dystrophies (n =2; 18.2%), glaucoma (n =1; 9.1%), and corneal scars (n =1; 9.1%). Higher prevalence of MSVI/blindness was associated with age (P < 0.001; odds ratio (OR)1.10; 95% CI 1.08, 1.12), male gender (P < 0.001; OR 2.32; 95% CI 1.47, 3.66), educational level (P < 0.001; OR 0.83; 95% CI 0.76,0.92), manual grip force (P < 0.001; OR 0.94; 95% CI 0.92, 0.96), diabetes prevalence (P = 0 .006; OR 1.67; 95% C11.08, 2.56) and axial length (P < 0.001; OR 1.43; 95% CI 1.26,1.62). In this population from Bashkortostan/Russia, prevalence of MVI, MSVI and blindness was 3.1%, 3.1% and 0.19%, respectively. Cataract was the most frequent cause of reversible vision impairment, while AMD, myopic maculopathy and glaucoma were the most common reasons for irreversible vision impairment.
C1 [Bikbov, Mukharram M.; Kazakbaeva, Gyulli M.; Zainullin, Rinat M.; Gilmanshin, Timur R.; Nuriev, Ildar F.; Zaynetdinov, Artur F.; Yakupova, Dilya F.; Uzianbaeva, Yulia, V; Mukhamadieva, Svetlana R.; Khikmatullin, Renat, I; Aminev, Said K.; Arslangareeva, Inga I.] Ufa Eye Res Inst, 90 Pushkin St, Ufa 450077, Bashkortostan, Russia.
   [Panda-Jonas, Songhomitra; Jonas, Jost B.] Heidelberg Univ, Dept Ophthalmol, Med Fac Mannheim, Theodor Kutzerufer 1, D-68167 Mannheim, Germany.
C3 Ufa Eye Research Institute; Ruprecht Karls University Heidelberg
RP Bikbov, MM (通讯作者)，Ufa Eye Res Inst, 90 Pushkin St, Ufa 450077, Bashkortostan, Russia.; Jonas, JB (通讯作者)，Heidelberg Univ, Dept Ophthalmol, Med Fac Mannheim, Theodor Kutzerufer 1, D-68167 Mannheim, Germany.
EM Bikbov.m@gmail.com; Jost.Jonas@medma.uni-heidelberg.de
RI Bikbov, Mukharram/AAO-7624-2021; Zainullin, Rinat/AAR-6362-2021
OI Kazakbaeva, Gyulli/0000-0002-0569-1264
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NR 24
TC 7
Z9 7
U1 0
U2 4
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 24
PY 2020
VL 10
IS 1
AR 12397
DI 10.1038/s41598-020-69439-4
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA MU1UQ
UT WOS:000555458800017
PM 32709931
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Korhonen, E
   Piippo, N
   Hytti, M
   Hyttinen, JMT
   Kaarniranta, K
   Kauppinen, A
AF Korhonen, Eveliina
   Piippo, Niina
   Hytti, Maria
   Hyttinen, Juha M. T.
   Kaarniranta, Kai
   Kauppinen, Anu
TI Only IL-1 beta release is inflammasome-dependent upon ultraviolet B
   irradiation although IL-18 is also secreted
SO FASEB JOURNAL
LA English
DT Article
DE DNA damage; NLRP3; IL-1 beta; IL-18; retinal pigment epithelium
ID PIGMENT EPITHELIAL-CELLS; UVB-INDUCED ACTIVATION; NUCLEAR-DNA DAMAGE;
   NLRP3 INFLAMMASOME; MACULAR DEGENERATION; OXIDATIVE STRESS;
   INTERLEUKIN-18; RADIATION; MITOCHONDRIAL; EXPRESSION
AB DNA damage accumulates in aged postmitotic retinal pigment epithelium (RPE) cells, a phenomenon associated with the development of age-related macular degeneration. In this study, we have experimentally induced DNA damage by ultraviolet B (UVB) irradiation in interleukin-1 alpha (IL-1 alpha)-primed ARPE-19 cells and examined inflammasome-mediated signaling. To reveal the mechanisms of inflammasome activation, cells were additionally exposed to high levels of extracellular potassium chloride, n-acetyl-cysteine, or mitochondria-targeted antioxidant MitoTEMPO, prior to UVB irradiation. Levels of interleukin-18 (IL-18) and IL-1 beta mRNAs were detected with qRT-PCR and secreted amounts of IL-1 beta, IL-18, and caspase-1 were measured with ELISA. The role of nucleotide-binding domain and leucine-rich repeat pyrin containing protein 3 (NLRP3) in UVB-induced inflammasome activation was verified by using the NLRP3-specific siRNA. Reactive oxygen species (ROS) levels were measured immediately after UVB exposure using the cell-permeant 2 ',7 '-dichlorodihydrofluorescein diacetate (H(2)DCFDA) indicator, the levels of cyclobutane pyrimidine dimers were assayed by cell-based ELISA, and the extracellular levels of adenosine triphosphate (ATP) determined using a commercial bioluminescence assay. We found that pro-IL-18 was constitutively expressed by ARPE-19 cells, whereas the expression of pro-IL-1 beta was inducible by IL-1 alpha priming. UVB induced the release of mature IL-18 and IL-1 beta but NLRP3 contributed only to the secretion of IL-1 beta. At the mechanistic level, the release of IL-1 beta was regulated by K+ efflux, whereas the secretion of IL-18 was dependent on ROS production. As well as K+ efflux, the cells released ATP following UVB exposure. Collectively, our data suggest that UVB clearly stimulates the secretion of mature IL-18 as a result of ROS induction, and this response is associated with DNA damage. Moreover, in human RPE cells, K+ efflux mediates the UVB-activated NLRP3 inflammasome signaling, leading to the processing of IL-1 beta.
C1 [Korhonen, Eveliina; Piippo, Niina; Hytti, Maria; Kauppinen, Anu] Univ Eastern Finland, Sch Pharm, Fac Hlth Sci, Kuopio, Finland.
   [Korhonen, Eveliina] Univ Helsinki, HUSLAB, Helsinki, Finland.
   [Korhonen, Eveliina] Helsinki Univ Hosp, Helsinki, Finland.
   [Hyttinen, Juha M. T.; Kaarniranta, Kai] Univ Eastern Finland, Inst Clin Med, Dept Ophthalmol, Kuopio, Finland.
   [Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, Kuopio, Finland.
C3 University of Eastern Finland; University of Helsinki; University of
   Helsinki; Helsinki University Central Hospital; University of Eastern
   Finland; Kuopio University Hospital; University of Eastern Finland
RP Korhonen, E; Kauppinen, A (通讯作者)，Univ Eastern Finland, Sch Pharm, Fac Hlth Sci, Kuopio, Finland.
EM eveliina.korhonen@uef.fi; anu.kauppinen@uef.fi
RI Hytti, Maria/AAE-4016-2019
OI Hytti, Maria/0000-0003-2150-6847; Korhonen,
   Eveliina/0000-0002-5360-7258; Hyttinen, Juha/0000-0002-3414-4032
FU Paivikki ja Sakari Sohlbergin Saatio (Paivikki and Sakari Sohlberg
   Foundation); Finnish Cultural Foundation \ Pohjois-Savon Rahasto (North
   Savo Regional Fund); Emil Aaltosen Saatio (Emil Aaltonen Foundation);
   Academy of Finland (Suomen Akatemia) [AK297267, AK307341, KK5503743];
   Sigrid Juseliuksen Saatio (Sigrid Juselius Stiftelse); University of
   Eastern Finland; Mary and Georg C. Ehrnrooth Foundation; Sokeain ystavat
   ry; Silma-ja Kudospankkisaatio
FX Paivikki ja Sakari Sohlbergin Saatio (Paivikki and Sakari Sohlberg
   Foundation); Finnish Cultural Foundation vertical bar Pohjois-Savon
   Rahasto (North Savo Regional Fund); Emil Aaltosen Saatio (Emil Aaltonen
   Foundation); Academy of Finland (Suomen Akatemia), Grant/Award Number:
   AK297267,AK307341 and KK5503743; Sigrid Juseliuksen Saatio (Sigrid
   Juselius Stiftelse); University of Eastern Finland strategical support;
   Mary and Georg C. Ehrnrooth Foundation; Sokeain ystavat ry; Silma-ja
   Kudospankkisaatio
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NR 59
TC 11
Z9 12
U1 1
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD MAY
PY 2020
VL 34
IS 5
BP 6437
EP 6448
DI 10.1096/fj.201902355RR
EA MAR 2020
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA LL1OX
UT WOS:000521549400001
PM 32190930
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Zhang, Z
   Hu, F
   Liu, Y
   Ma, B
   Chen, X
   Zhu, K
   Shi, Y
   Wei, T
   Xing, Y
   Gao, Y
   Lu, H
   Liu, Y
   Kang, Q
AF Zhang, Z.
   Hu, F.
   Liu, Y.
   Ma, B.
   Chen, X.
   Zhu, K.
   Shi, Y.
   Wei, T.
   Xing, Y.
   Gao, Y.
   Lu, H.
   Liu, Y.
   Kang, Q.
TI ACTIVATION OF TYPE 5 METABOTROPIC GLUTAMATE RECEPTOR PROMOTES THE
   PROLIFERATION OF RAT RETINAL PROGENITOR CELL VIA ACTIVATION OF THE
   PI-3-K AND MAPK SIGNALING PATHWAYS
SO NEUROSCIENCE
LA English
DT Article
DE retinal progenitor cells; metabotropic glutamate receptor 5;
   proliferation; mitogen-activated protein kinases;
   phosphatidylinositol-3-kinase
ID NEURAL STEM-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASES; ERK;
   DIFFERENTIATION; PAIN; AKT; NEUROGENESIS; DOWNSTREAM; SUBTYPE-5
AB The metabotropic glutamate receptor 5 (mGluR5) regulates neurogenesis in the brain, but the effect of mGluR5 on retinal progenitor cells (RPCs) remains unknown. In this study, we found that mGluR5 promoted the proliferation of rat RPCs with activation of the phosphatidylinositol-3-kinase (PI-3-K) and mitogen-activated protein kinase (MAPK) signaling pathways in vitro. The mGluR5 agonist (S)-3,5-dihydroxyphenylglycine hydrate (DHPG) increased the cellular viability in a concentration-and time-dependent manner, whereas the mGluR5 antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride (MTEP) had the opposite effect, as shown by 3-((2-methyl-1,3-thiazol-4-yl) ethynyl)pyridine hydrochloride (MTT) assay. Treatment with DHPG (100 mu M) also promoted the proliferation of RPCs, as indicated by 5-Bromo-2-deoxyUridine (BrdU) staining and flow cytometry, and likewise, MTEP (100 mu M) and mGluR5 knockdown abolished the action of mGluR5 activity. Western blot demonstrated that the activation of mGluR5 enhanced the expression of Cyclin D1 and the phosphorylation level of PKC however, MTEP or mGluR5 knockdown also abrogated the effect of DHPG on RPCs. Furthermore, we found that activation of the extracellular signal-regulated protein kinase (ERK) and protein kinase B (AKT) signaling pathways was involved in the proliferation of RPC. After DHPG treatment, the levels of both p-ERK1/2 and p-AKT increased in a time-dependent manner. Then we used MTEP, mGluR5 knockdown, the ERK1/2 inhibitor U0126 and the AKT inhibitor LY294002 to pretreat the cells, and all of them clearly eliminated the influence of DHPG. These results demonstrated that mGluR5 regulates neurogenesis in RPCs through the MAPK and PI-3-K signaling pathways, and these findings may motivate a pharmacological study investigating a potential mechanism for the treatment of retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Hu, F.; Ma, B.; Shi, Y.; Wei, T.; Xing, Y.; Kang, Q.] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Ophthalmol, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China.
   [Zhang, Z.; Liu, Y.; Chen, X.; Zhu, K.; Gao, Y.; Lu, H.; Liu, Y.] Xi An Jiao Tong Univ, Hlth Sci Ctr, Inst Neurobiol, 76 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China.
   [Hu, F.] Ningbo Med Treatment Ctr Lihuili Hosp, Ningbo 315040, Zhejiang, Peoples R China.
C3 Xi'an Jiaotong University; Xi'an Jiaotong University
RP Kang, Q (通讯作者)，Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Ophthalmol, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China.; Liu, Y (通讯作者)，Xi An Jiao Tong Univ, Hlth Sci Ctr, Inst Neurobiol, 76 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China.
EM liuy5599@mail.xjtu.edu.cn; kangqy@mail.xjtu.edu.cn
RI han, arzu/G-6630-2016
OI han, arzu/0000-0002-1480-4072
FU National Natural Science Foundation of China [81371348, 30772373];
   Science and Technology Development Project of Shaanxi Province
   [2012K16-11(04), 2011K14-07(09)]; Natural Science Foundation of Shaanxi
   Province Department of Health [2010D22]
FX This work was supported by grants from National Natural Science
   Foundation of China (Nos. 81371348, 30772373), the Science and
   Technology Development Project of Shaanxi Province [Nos. 2012K16-11(04),
   2011K14-07(09)] and the Natural Science Foundation of Shaanxi Province
   Department of Health (2010D22).
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NR 50
TC 24
Z9 24
U1 0
U2 36
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD MAY 13
PY 2016
VL 322
BP 138
EP 151
DI 10.1016/j.neuroscience.2016.02.030
PG 14
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA DG8QX
UT WOS:000372349800013
PM 26902516
DA 2022-11-30
ER

PT J
AU Lim, DK
   Wylie, RG
   Langer, R
   Kohane, DS
AF Lim, Dong-Kwon
   Wylie, Ryan G.
   Langer, Robert
   Kohane, Daniel S.
TI Selective binding of C-6 OH sulfated hyaluronic acid to the angiogenic
   isoform of VEGF(165)
SO BIOMATERIALS
LA English
DT Article
DE Vascular endothelial growth factor 165; VEGF(165a); VEGF(165b);
   Angiogenesis; Sulfated sodium hyaluronate; Selective binding property
ID ENDOTHELIAL GROWTH-FACTOR; SPLICE VARIANT; VEGF; BEVACIZUMAB;
   EXPRESSION; PEGAPTANIB; FRAGMENT; ANTIBODY; THERAPY; APTAMER
AB Vascular endothelial growth factor 165 (VEGF(165)) is an important extracellular protein involved in pathological angiogenesis in diseases such as cancer, wet age-related macular degeneration (wet-AMD) and retinitis pigmentosa. VEGF(165) exists in two different isoforms: the angiogenic VEGF-(165a), and the anti-angiogenic VEGF(165b). In some angiogenic diseases the proportion of VEGF(165b) may be equal to or higher than that of VEGF(165a). Therefore, developing therapeutics that inhibit VEGF(165a) and not VEGF(165b) may result in greater anti-angiogenic activity and therapeutic benefit. To this end, we report the selective binding properties of sulfated hyaluronic acid (s-HA). Selective biopolymers offer several advantages over antibodies or aptamers including cost effective and simple synthesis, and the ability to make nano-particles or hydrogels for drug delivery applications or VEGF(165a) sequestration. Limiting sulfation to the C-6 hydroxyl (C-6 OH) in the N-acetyl-glucosamine repeat unit of hyaluronic acid (HA) resulted in a polymer with strong affinity for VEGF(165a) but not VEGF(165b). Increased sulfation beyond the C-6 OH (i.e. greater than 1 sulfate group per HA repeat unit) resulted in s-HA polymers that bound both VEGF(165a) and VEGF(165b). The C-6 OH sulfated HA (Mw 150 kDa) showed strong binding properties to VEGF(165a) with a fast association rate constant (K-a; 2.8 x 10(6) M-1 s(-1)), slow dissociation rate constant (K-d; 2.8 x 10(-3) s(-1)) and strong equilibrium binding constant (K-D); similar to 1.0 nM)), which is comparable to the non-selective VEGF(165) binding properties of the commercialized therapeutic anti-VEGF antibody (Avastin (R)). The C-6 OH sulfated HA also inhibited human umbilical vein endothelial cell (HUVEC) survival and proliferation and human dermal microvascular endothelial cell (HMVEC) tube formation. These results demonstrate that the semi-synthetic natural polymer, C-6 OH sulfated HA, may be a promising biomaterial for the treatment of angiogenesis-related disease. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Lim, Dong-Kwon] Korea Univ, KU KIST Grad Sch Converging Sci & Technol, Seoul, South Korea.
   [Wylie, Ryan G.] McMaster Univ, Dept Chem & Chem Biol, Hamilton, ON L8S 4M1, Canada.
   [Langer, Robert] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Lim, Dong-Kwon; Wylie, Ryan G.; Kohane, Daniel S.] Harvard Univ, Sch Med, Boston Childrens Hosp, Lab Biomat & Drug Delivery,Dept Anesthesiol,Div C, Boston, MA 02115 USA.
C3 Korea University; McMaster University; Massachusetts Institute of
   Technology (MIT); Harvard University; Boston Children's Hospital;
   Harvard Medical School
RP Kohane, DS (通讯作者)，Harvard Univ, Sch Med, Boston Childrens Hosp, 300 Longwood Ave,Enders 361, Boston, MA 02115 USA.
EM daniel.kohane@childrens.harvard.edu
FU Sanofi-Aventis; NIH [DE013023, GM073626]; Banting Postdoctoral
   Fellowship from the Natural Sciences and Engineering Research Council of
   Canada; NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
   [R01DE013023] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   GENERAL MEDICAL SCIENCES [R01GM073626] Funding Source: NIH RePORTER
FX This work was supported by grants from Sanofi-Aventis, NIH Grant #
   DE013023 (R L.) and NIH Grant # GM073626 (D.S.K). RGW also thanks the
   support of the Banting Postdoctoral Fellowship from the Natural Sciences
   and Engineering Research Council of Canada.
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NR 35
TC 27
Z9 28
U1 3
U2 82
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD JAN
PY 2016
VL 77
BP 130
EP 138
DI 10.1016/j.biomaterials.2015.10.074
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA CZ5BV
UT WOS:000367118200012
PM 26588795
OA Green Accepted, Green Submitted
DA 2022-11-30
ER

PT J
AU Bunce, C
   Xing, W
   Wormald, R
AF Bunce, C.
   Xing, W.
   Wormald, R.
TI Causes of blind and partial sight certifications in England and Wales:
   April 2007-March 2008
SO EYE
LA English
DT Article
DE blind; registration; age-related macular degeneration; glaucoma;
   diabetic retinopathy
ID UNREGISTERED VISUAL IMPAIRMENT; REGISTRATION
AB Purpose The last complete report on causes of blindness in England and Wales was for the data collected during April 1999-March 2000. This study updates these figures, with data collected during April 2007-March 2008.
   Methods In England and Wales, registration for blindness and partial sight is initiated with certification by a consultant ophthalmologist with the consent of the patient. The main cause of visual impairment was ascertained where possible for all certificates completed during April 2007-March 2008 and a proportional comparison with 1999-2000 figures was made.
   Results We received 23 185 Certificates of Vision Impairment (CVIs), of which 9823 were for severe sight impairment (blindness) (SSI) and 12 607 were for sight impairment (partial sight) (SI). These totals were considerably lower than the numbers certified in the year ending 31 March 2000. In 16.6% of CVIs, there were multiple causes of visual impairment as compared with 3% of BD8s in 2000. Degeneration of the macula and posterior pole (mostly age-related macular degeneration (AMD)) contributed to vision impairment in 12 746 newly certified blind or partially sighted.
   Conclusions AMD is still by far the leading cause of certified visual loss in England and Wales. Proportional comparisons are hampered by the increasing use of multiple pathology as a main cause of visual impairment, which is believed to have arisen owing to the change in certificate used for data collection. These figures are not estimates of the total numbers newly blind in the UK because not all those entitled to certification are offered and or accept it, but they do nevertheless document the number of people who are deemed to be sufficiently sight impaired to warrant support and have been both offered and accepted it. This is usually the case when no further ophthalmic intervention is thought likely to be of benefit in terms of restoring or improving vision. Eye (2010) 24, 1692-1699; doi: 10.1038/eye.2010.122; published online 17 September 2010
C1 [Bunce, C.; Xing, W.; Wormald, R.] Moorfields Eye Hosp, London EC1V 2PD, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust
RP Bunce, C (通讯作者)，Moorfields Eye Hosp, City Rd, London EC1V 2PD, England.
EM c.bunce@ucl.ac.uk
OI Bunce, Catey/0000-0002-0935-3713
FU Guide Dogs and R D
FX This study was supported by a grant from the Guide Dogs and R & D
   central funding. The data captured by the CVI are DH copyright and this
   work was made possible by collaboration with the Royal College of
   Ophthalmologists.
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NR 17
TC 123
Z9 126
U1 1
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD NOV
PY 2010
VL 24
IS 11
BP 1692
EP 1699
DI 10.1038/eye.2010.122
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 678WF
UT WOS:000284112900009
PM 20847749
OA Bronze
DA 2022-11-30
ER

PT J
AU Yu, AL
   Fuchshofer, R
   Kook, D
   Kampik, A
   Bloemendal, H
   Welge-Luessen, U
AF Yu, Alice L.
   Fuchshofer, Rudolf
   Kook, Daniel
   Kampik, Anselm
   Bloemendal, Hans
   Welge-Luessen, Ulrich
TI Subtoxic Oxidative Stress Induces Senescence in Retinal Pigment
   Epithelial Cells via TGF-beta Release
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID TISSUE GROWTH-FACTOR; HUMAN-DIPLOID FIBROBLASTS; HUMAN SKIN FIBROBLASTS;
   PREMATURE SENESCENCE; EXTRACELLULAR-MATRIX; MACULAR DEGENERATION;
   TRABECULAR MESHWORK; GENE-EXPRESSION; INDUCTION; DRUSEN
AB PURPOSE. The goal of the present study was to determine whether oxidative stress and transforming growth factor (TGF)-beta induce cellular senescence in human retinal pigment epithelial (RPE) cells.
   METHODS. Cultured human RPE cells were exposed to 50 to 150 mu M hydrogen peroxide (H2O2) for 1 and 2 hours or treated with 1.0 ng/ mL TGF-beta 1 or -beta 2 for 12, 24, and 48 hours. Senescence-associated beta-galactosidase (SA-beta-Gal) activity was detected by histochemical staining. Expression of senescence-associated genes (apolipoprotein J [Apo J], connective tissue growth factor [CTGF], fibronectin, and SM22) was examined by real-time PCR and induction of signal transduction proteins (p21, p16, and pRb) by Western blot analysis. The effects of TGF-beta blocking on the oxidative stress-induced expression of senescence-associated biomarkers were investigated by simultaneous incubation with neutralizing antibodies against the TGF-beta 1, -beta 2, and -beta 3 isoforms and the TGF-beta II receptor.
   RESULTS. H2O2 markedly increased the number of SA-beta-Gal-positive cells to up to 89% and the expression of Apo J, CTGF, fibronectin, and SM22 by approximately three to fourfold. Treatment with TGF-beta 1 and -beta 2 showed similar changes. H2O2 and TGF-beta 1 and -beta 2 markedly enhanced the expression of p21 but downregulated pRb. In contrast, they had no effect on p16 expression. Simultaneous treatment with neutralizing antibodies against the TGF-beta 1, -beta 2, and -beta 3 isoforms and the TGF-beta II receptor prevented the oxidative stress-mediated elevation of senescence-associated biomarkers.
   CONCLUSIONS. Oxidative stress, TGF-beta 1, and TGF-beta 2 are capable of inducing cellular senescence in cultured human RPE cells. Therefore, reduction of oxidative stress and minimizing TGF-beta may help to prevent senescence-associated changes in the RPE as seen in early age-related macular degeneration. (Invest Ophthalmol Vis Sci. 2009; 50: 926-935) DOI: 10.1167/iovs.07-1003
C1 [Welge-Luessen, Ulrich] Univ Erlangen Nurnberg, Dept Ophthalmol, D-91054 Erlangen, Germany.
   [Yu, Alice L.; Kook, Daniel; Kampik, Anselm; Welge-Luessen, Ulrich] Univ Munich, Dept Ophthalmol, Munich, Germany.
   [Fuchshofer, Rudolf] Univ Regensburg, Dept Anat, Regensburg, Germany.
   [Bloemendal, Hans] Radboud Univ Nijmegen, Dept Biomol Chem NGMLS, Nijmegen, Netherlands.
C3 University of Erlangen Nuremberg; University of Munich; University of
   Regensburg; Radboud University Nijmegen
RP Welge-Luessen, U (通讯作者)，Univ Erlangen Nurnberg, Dept Ophthalmol, Schwabachanlage 6, D-91054 Erlangen, Germany.
EM ulrich.welge@uk-erlangen.de
RI Kook, Daniel/AAU-8717-2021; Daniel Kook, Kook/G-6071-2012; Fuchshofer,
   Rudolf/E-8221-2010; Fuchshofer, Rudolf/M-3712-2019
OI Fuchshofer, Rudolf/0000-0002-0474-6980; Fuchshofer,
   Rudolf/0000-0002-0474-6980
FU DFG [WE 2577/2-1]; DOG Research Support (UWL)
FX Supported by Grant DFG WE 2577/2-1 and DOG Research Support (UWL).
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NR 54
TC 62
Z9 64
U1 0
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2009
VL 50
IS 2
BP 926
EP 935
DI 10.1167/iovs.07-1003
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 397MD
UT WOS:000262665900056
PM 19171648
DA 2022-11-30
ER

PT J
AU Reboul, E
   Abou, L
   Mikail, C
   Ghiringhelli, O
   Andre, M
   Portugal, H
   Jourdheuil-Rahmani, D
   Amiot, MJ
   Lairon, D
   Borel, P
AF Reboul, E
   Abou, L
   Mikail, C
   Ghiringhelli, O
   Andre, M
   Portugal, H
   Jourdheuil-Rahmani, D
   Amiot, MJ
   Lairon, D
   Borel, P
TI Lutein transport by Caco-2 TC-7 cells occurs partly by a facilitated
   process involving the scavenger receptor class B type I (SR-BI)
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE Caco-2 TC-7 cells; carotenoid; cluster determinant 36 (CD36); lutein;
   scavenger receptor class B type 1 (SR-BI); xanthophyll
ID APPARENT DRUG PERMEABILITY; FATTY-ACID UPTAKE; BETA-CAROTENE;
   INTESTINAL-ABSORPTION; CHOLESTEROL ABSORPTION; HUMAN STOMACH;
   ZEAXANTHIN; LINE; MECHANISMS; IDENTIFICATION
AB The carotenoid lutein is thought to play a role in the human eye and to protect against age-related macular degeneration. Lutein transport in the human intestine has not been characterized. We examined Intent transport processes using Caco-2 TC-7 mono-layers as a model for human intestinal epithelium. Purified lutein was mixed with phospholipids, lysophospholipids, cholesterol, mono-olefin. oleic acid and taurocholate to obtain lutein-rich mixed micelles that mimicked those found under physiological conditions. The micelles were added to the apical side of Caco-2 TC-7 cell monolayers for 30 min or 3 h at 37 degrees C. Absorbed lutein, i.e. the sum of lutein recovered in the scraped cells and in the basolateral chamber, was quantified by HPLC. Transport rate was measured (i) as a function of time (from 15 to 60 min), (ii) as a function of micellar Intent concentration (froth 1.5 to 15 mu M), (iii) at 4 degrees C, (iv) in the basolateral to apical direction, (v) after trypsin pretreatment, (vi) in the presence of beta-carotene and/or lycopene, (vii) in the presence of increasing concentrations of antibody against SR-BI (scavenger receptor class B type 1) and (viii) in the presence of increasing concentrations of a chemical inhibitor of the selective transfer of lipids mediated by SR-BI, i.e. BLT 1 (blocks lipid transport 1). The rate of transport of lutein as a function of time and as a function of concentration was saturable. It was significantly lower at 4 degrees C than at 37 degrees C (approx. 50%), in the basal to apical direction than in the opposite direction (approx. 85 %), and after trypsin pretreatment (up to 45 %). Coincubation with beta-carotene, but not lycopene, decreased the lutein absorption rate (approx. 20%) significantly. Anti-SR-BI antibody and BLT I significantly impaired the absorption rate (approx. 30 % and 57 % respectively). Overall, these results indicate that lutein absorption is, at least partly, protein-mediated and that some lutein is taken up through SR-BI.
C1 Fac Med Marseille, INSERM, UMR 476, F-13385 Marseille, France.
   INRA 1260, F-13385 Marseille, France.
   Univ Aix Marseille 1, F-13385 Marseille, France.
   IPHM, F-13385 Marseille, France.
   Fac Pharm Marseille, Chim Analyt Serv, F-13005 Marseille, France.
   Fac Pharm Marseille, Lab Biochim & Semiol Clin, F-13005 Marseille, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Aix-Marseille Universite; INRAE;
   UDICE-French Research Universities; Aix-Marseille Universite;
   UDICE-French Research Universities; Aix-Marseille Universite
RP Borel, P (通讯作者)，Fac Med Marseille, INSERM, UMR 476, 27 Bd Jean Moulin, F-13385 Marseille, France.
EM Patrick.Borel@medecine.univ-mrs.fr
RI Borel, Patrick/A-4057-2015; Reboul, Emmanuelle/K-6637-2017; Amiot, Marie
   Josephe/M-1203-2017; Amiot, Marie Josephe/C-4457-2015; AMIOT, MARIE
   JOSEPHE/N-8894-2019
OI Borel, Patrick/0000-0001-9977-3238; Reboul,
   Emmanuelle/0000-0002-4576-1992; Amiot, Marie
   Josephe/0000-0003-4563-4587; AMIOT, MARIE JOSEPHE/0000-0003-4563-4587;
   Lairon, Denis/0000-0001-9941-3742
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NR 48
TC 202
Z9 207
U1 7
U2 39
PU PORTLAND PRESS LTD
PI LONDON
PA 5TH FLR, 90 HIGH HOLBORN, LONDON WC1V 6LJ, ENGLAND
SN 0264-6021
EI 1470-8728
J9 BIOCHEM J
JI Biochem. J.
PD APR 15
PY 2005
VL 387
BP 455
EP 461
DI 10.1042/BJ20040554
PN 2
PG 7
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 920OE
UT WOS:000228699200019
PM 15554873
OA Green Published
DA 2022-11-30
ER

PT J
AU Seddon, JM
   Sharma, S
   Chong, S
   Hutchinson, A
   Allikmets, R
   Adelman, RA
AF Seddon, JM
   Sharma, S
   Chong, S
   Hutchinson, A
   Allikmets, R
   Adelman, RA
TI Phenotype and genotype correlations in two best families
SO OPHTHALMOLOGY
LA English
DT Article
ID BEST-DISEASE GENE; MACULAR DYSTROPHY; VITELLIFORM DYSTROPHY;
   DEGENERATION
AB Objective: To evaluate mutations in the Best mascular dystrophy (VMD2) gene in two families with Best disease and to describe the phenotype-genotype correlations of genetically determined affected and unaffected individuals.
   Design: Family genetic study.
   Participants: Two families with Best disease were identified, and family members were evaluated by ophthalmologic examination or fundus photography to assess their phenotype. All affected patients and some of the unaffected family members had a blood sample drawn, and the DNA was analyzed for mutations in the VMD2 gene.
   Main Outcome Measures: Twenty-one subjects in the two pedigrees with Best disease were studied. One amino acid-changing mutation in the VMD2 gene was found to segregate independently in each family (P297S or E300D, respectively).
   Results: Eleven individuals had some evidence of maculopathy, including retinal pigment epithelial changes, drusen, pigment epithelial irregularities, or cicatricial changes. Ten of these 11 patients (91%) with maculopathy had a mutation in the VMD2 gene, of whom 8 were clinically diagnosed as having Best disease and 2 were diagnosed as having possible Best maculopathy. The one patient without a mutation in the VMD2 gene had age-related macular degeneration (AMD). Ten family members did not have evidence of maculopathy, of whom 6 had no mutation in the VMD2 gene. Four family members (2 in each pedigree) had mutations in the VMD2 gene, abnormal electro-oculogram (EOG) results, but normal maculae at age 40 or older. Of the 7 individuals with no mutation in the VMD2 gene, 6 were phenotypically normal and the other had late-onset visual loss resulting from AMD.
   Conclusions: All family members with maculopathy consistent with Best disease (n = 10) had an amino acid-changing mutation in the VMD2 gene. Four individuals who did not have maculopathy, but did have an abnormal EOG, also had mutations in the VMD2 gene. The presence of a VMD2 mutation is associated with abnormal retinal function, which can occur in the absence of phenotypic manifestation of macular disease. (C) 2003 by the American Academy of Ophthalmology.
C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit,Dept Ophthalmol, Boston, MA 02114 USA.
   Queens Univ, Kingston, ON, Canada.
   Columbia Univ, Dept Ophthalmol, New York, NY USA.
   Columbia Univ, Dept Pathol, New York, NY USA.
   Yale Univ, Ctr Eye, New Haven, CT USA.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Queens University - Canada; Columbia University; Columbia
   University; Yale University
RP Seddon, JM (通讯作者)，Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
RI Allikmets, Rando/ABD-4533-2021
FU NEI NIH HHS [R01 EY011309, EY11309, EY13435] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [R01EY013435] Funding Source: NIH RePORTER
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NR 16
TC 31
Z9 33
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD SEP
PY 2003
VL 110
IS 9
BP 1724
EP 1731
DI 10.1016/S0161-6420(03)00575-X
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 715BG
UT WOS:000184950200011
PM 13129869
DA 2022-11-30
ER

PT J
AU Balaskas, K
   Glinton, S
   Keenan, TDL
   Faes, L
   Liefers, B
   Zhang, G
   Pontikos, N
   Struyven, R
   Wagner, SK
   McKeown, A
   Patel, PJ
   Keane, PA
   Fu, DJ
AF Balaskas, Konstantinos
   Glinton, S.
   Keenan, T. D. L.
   Faes, L.
   Liefers, B.
   Zhang, G.
   Pontikos, N.
   Struyven, R.
   Wagner, S. K.
   McKeown, A.
   Patel, P. J.
   Keane, P. A.
   Fu, D. J.
TI Prediction of visual function from automatically quantified optical
   coherence tomography biomarkers in patients with geographic atrophy
   using machine learning
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; ACUITY; REPEATABILITY; VISION
AB Geographic atrophy (GA) is a vision-threatening manifestation of age-related macular degeneration (AMD), one of the leading causes of blindness globally. Objective, rapid, reliable, and scalable quantification of GA from optical coherence tomography (OCT) retinal scans is necessary for disease monitoring, prognostic research, and clinical endpoints for therapy development. Such automatically quantified biomarkers on OCT are likely to further elucidate structure-function correlation in GA and thus the pathophysiological mechanisms of disease development and progression. In this work, we aimed to predict visual function with machine-learning applied to automatically acquired quantitative imaging biomarkers in GA. A post-hoc analysis of data from a clinical trial and routine clinical care was conducted. A deep-learning automated segmentation model was applied on OCT scans from 476 eyes (325 patients) with GA. A separate machine learning prediction model (Random Forest) used the resultant quantitative OCT (qOCT) biomarkers to predict cross-sectional visual acuity under standard (VA) and low luminance (LLVA). The primary outcome was regression coefficient (r(2)) and mean absolute error (MAE) for cross-sectional VA and LLVA in Early Treatment Diabetic Retinopathy Study (ETDRS) letters. OCT parameters were predictive of VA (r(2) 0.40 MAE 11.7 ETDRS letters) and LLVA (r(2) 0.25 MAE 12.1). Normalised random forest feature importance, as a measure of the predictive value of the three constituent features of GA; retinal pigment epithelium (RPE)-loss, photoreceptor degeneration (PDR), hypertransmission and their locations, was reported both on voxel-level heatmaps and ETDRS-grid subfields. The foveal region (46.5%) and RPE-loss (31.1%) had greatest predictive importance for VA. For LLVA, however, non-foveal regions (74.5%) and PDR (38.9%) were most important. In conclusion, automated qOCT biomarkers demonstrate predictive significance for VA and LLVA in GA. LLVA is itself predictive of GA progression, implying that the predictive qOCT biomarkers provided by our model are also prognostic.
C1 [Balaskas, Konstantinos; Glinton, S.; Faes, L.; Liefers, B.; Zhang, G.; Pontikos, N.; Struyven, R.; Wagner, S. K.; Patel, P. J.; Keane, P. A.; Fu, D. J.] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, UCL Inst Ophthalmol, Moorfields Reading Ctr & Clin AI Hub, 162 City Rd, London EC1V 2PD, England.
   [Keenan, T. D. L.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
   [McKeown, A.] Apellis Pharmaceut Inc, Waltham, MA USA.
   [Liefers, B.] Erasmus Univ, Med Ctr, Dept Ophthalmol, Rotterdam, Netherlands.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; National Institutes of Health (NIH) - USA; NIH
   National Eye Institute (NEI); Erasmus University Rotterdam; Erasmus MC
RP Balaskas, K (通讯作者)，Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, UCL Inst Ophthalmol, Moorfields Reading Ctr & Clin AI Hub, 162 City Rd, London EC1V 2PD, England.
EM k.balaskas@nhs.net
RI Balaskas, Konstantinos/ABD-5979-2020
OI Balaskas, Konstantinos/0000-0002-7690-6277; McKeown,
   Alex/0000-0002-5075-3532; Keane, Pearse/0000-0002-9239-745X
FU Apellis Pharmaceuticals (Waltham, Massachusetts, United States)
FX Apellis Pharmaceuticals (Waltham, Massachusetts, United States) provided
   financial support and critical review of manuscript for publication.
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NR 43
TC 0
Z9 0
U1 0
U2 0
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD SEP 16
PY 2022
VL 12
IS 1
AR 15565
DI 10.1038/s41598-022-19413-z
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 4O6GX
UT WOS:000854795000020
PM 36114218
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Qu, SC
   Zhang, CY
   Liu, DD
   Wu, J
   Tian, HB
   Lu, LX
   Xu, GT
   Liu, F
   Zhang, JF
AF Qu, Sichang
   Zhang, Chaoyang
   Liu, Dandan
   Wu, Jing
   Tian, Haibin
   Lu, Lixia
   Xu, Guo-Tong
   Liu, Fang
   Zhang, Jingfa
TI Metformin Protects ARPE-19 Cells from Glyoxal-Induced Oxidative Stress
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; NITRIC-OXIDE; MACULAR DEGENERATION; AMPK;
   PREVALENCE; EXPRESSION; AUTOPHAGY; DISEASE; NRF2
AB The protective effects and mechanisms of metformin against oxidative stress were evaluated bothin vivoandin vitro. ARPE-19 cells comprised the normal group, the glyoxal-treated group (0.5 mM glyoxal), and the glyoxal+metformin group (0.5 mM glyoxal and 0.1 mM metformin). In thein vitromodel, differences in cell viability, ROS production, NO products, cellular apoptosis, and the expressions of phospho-AMPK alpha, total-AMPK alpha, Sirt1, Nrf2, TXNIP, ZO-1, and Occludin were assessed. In the glyoxal-treated group, cell viability and NO production were decreased, while ROS production and cell apoptosis were increased (p<0.05), compared with the control group. These changes were prevented by metformin treatment. Protein expressions of phospho-AMPK alpha, Sirt1, TXNIP, ZO-1, and Occludin, but not Nrf2, were decreased significantly in the glyoxal-treated group compared to normal controls. Metformin treatment significantly increased the above protein expressions and slightly increased TXNIP expression. Immunofluorescence showed that metformin prevented the glyoxal-induced, disorganized tight junctions in ARPE-19 cells. To confirm metformin's protection, Sprague-Dawley rats were injected intravenously with sodium iodate (SI) to induce oxidative stress in the retinal pigment epithelium (RPE). Metformin was then delivered intraperitoneally or intravitreally. One day and three days after SI and metformin treatments, the RPE-Bruch's membrane-choriocapillaris complex was isolated and immune-stained with ZO-1 antibodies. The morphology of the RPE showed enlarged cellular bodies and disorganized ZO-1 staining in SI-treated rats. Metformin treatment prevented these changes. The results indicated that metformin maintained the barrier functions of RPE cells bothin vivoandin vitro. Metformin exerted its protection against oxidative stress possibly via activating AMPK/Sirt1 and increasing TXNIP. Metformin has been proposed as a candidate drug for age-related macular degeneration (AMD) by both preclinical and clinical studies. The cellular and animal models used in this study might be useful for the interpretation of the molecular mechanisms involved in the drug activity.
C1 [Qu, Sichang; Zhang, Chaoyang; Liu, Dandan; Wu, Jing; Tian, Haibin; Lu, Lixia; Xu, Guo-Tong; Liu, Fang; Zhang, Jingfa] Tongji Univ, Shanghai Peoples Hosp 10, Tongji Eye Inst, Dept Regenerat Med,Sch Med,Dept Ophthalmol, Shanghai, Peoples R China.
   [Qu, Sichang; Zhang, Chaoyang; Liu, Dandan; Wu, Jing; Tian, Haibin; Lu, Lixia; Xu, Guo-Tong; Liu, Fang; Zhang, Jingfa] Tongji Univ, Sch Med, Dept Pharmacol, Shanghai, Peoples R China.
   [Zhang, Jingfa] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Shanghai Gen Hosp, Dept Ophthalmol, Shanghai, Peoples R China.
   [Zhang, Jingfa] Natl Clin Res Ctr Eye Dis, Shanghai, Peoples R China.
   [Zhang, Jingfa] Shanghai Key Lab Ocular Fundus Dis, Shanghai, Peoples R China.
   [Zhang, Jingfa] Shanghai Engn Ctr Visual Sci & Photomed, Shanghai, Peoples R China.
   [Zhang, Jingfa] Shanghai Engn Ctr Precise Diag & Treatment Eye Di, Shanghai, Peoples R China.
C3 Tongji University; Tongji University; Shanghai Jiao Tong University
RP Liu, F; Zhang, JF (通讯作者)，Tongji Univ, Shanghai Peoples Hosp 10, Tongji Eye Inst, Dept Regenerat Med,Sch Med,Dept Ophthalmol, Shanghai, Peoples R China.; Liu, F; Zhang, JF (通讯作者)，Tongji Univ, Sch Med, Dept Pharmacol, Shanghai, Peoples R China.; Zhang, JF (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Shanghai Gen Hosp, Dept Ophthalmol, Shanghai, Peoples R China.; Zhang, JF (通讯作者)，Natl Clin Res Ctr Eye Dis, Shanghai, Peoples R China.; Zhang, JF (通讯作者)，Shanghai Key Lab Ocular Fundus Dis, Shanghai, Peoples R China.; Zhang, JF (通讯作者)，Shanghai Engn Ctr Visual Sci & Photomed, Shanghai, Peoples R China.; Zhang, JF (通讯作者)，Shanghai Engn Ctr Precise Diag & Treatment Eye Di, Shanghai, Peoples R China.
EM fangliu_2004@yahoo.com; 13917311571@139.com
FU National Natural Science Foundation of China [81570852, 81970810,
   81970811]; Clinical Research and Cultivation Project of Shanghai
   Municipal Hospital [SHDC12019X30]
FX This study was supported by the National Natural Science Foundation of
   China (grant number 81570852, 81970810, 81970811) and Clinical Research
   and Cultivation Project of Shanghai Municipal Hospital (grant number
   SHDC12019X30).
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NR 50
TC 16
Z9 16
U1 2
U2 10
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1942-0900
EI 1942-0994
J9 OXID MED CELL LONGEV
JI Oxidative Med. Cell. Longev.
PD JUL 10
PY 2020
VL 2020
AR 1740943
DI 10.1155/2020/1740943
PG 12
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA MR1YL
UT WOS:000553387100004
PM 32695253
DA 2022-11-30
ER

PT J
AU Elsner, AE
   Papay, JA
   Johnston, KD
   Sawides, L
   de Castro, A
   King, BJ
   Jones, DW
   Clark, CA
   Gast, TJ
   Burns, SA
AF Elsner, Ann E.
   Papay, Joel A.
   Johnston, Kirby D.
   Sawides, Lucie
   de Castro, Alberto
   King, Brett J.
   Jones, Durand W.
   Clark, Christopher A.
   Gast, Thomas J.
   Burns, Stephen A.
TI Cones in ageing and harsh environments: the neural economy hypothesis
SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS
LA English
DT Article
DE ageing; age-related macular degeneration; cones; photoreceptor; retinal
   pigment epithelial cell complex; retinal degeneration
ID PHOTORECEPTOR PACKING DENSITY; SCANNING LASER OPHTHALMOSCOPE; ON-YELLOW
   PERIMETRY; GEOGRAPHIC ATROPHY; IMAGING POLARIMETRY; VISUAL-ACUITY;
   IN-VIVO; SUBRETINAL STRUCTURES; IMPROVED CONTRAST; PHOTOPIGMENT
AB Purpose Cones are at great risk in a wide variety of retinal diseases, especially when there is a harsh microenvironment and retinal pigment epithelium is damaged. We provide established and new methods for assessing cones and retinal pigment epithelium, together with new results. We investigated conditions under which cones can be imaged and could guide light, despite the proximity of less than ideal retinal pigment epithelium.
   Recent findings We used a variety of imaging methods to detect and localise damage to the retinal pigment epithelium. As age-related macular degeneration is a particularly widespread disease, we imaged clinical hallmarks: drusen and hyperpigmentation. Using near infrared light provided improved imaging of the deeper fundus layers. We compared confocal and multiply scattered light images, using both the variation of detection apertures and polarisation analysis. We used optical coherence tomography to examine distances between structures and thickness of retinal layers, as well as identifying damage to the retinal pigment epithelium. We counted cones using adaptive optics scanning laser ophthalmoscopy. We compared the results of five subjects with geographic atrophy to data from a previous normative ageing study.
   Using near infrared imaging and layer analysis of optical coherence tomography, the widespread aspect of drusen became evident. Both multiply scattered light imaging and analysis of the volume in the retinal pigment epithelial layer from the optical coherence tomography were effective in localising drusen and hyperpigmentation beneath the photoreceptors. Cone photoreceptors in normal older eyes were shorter than in younger eyes. Cone photoreceptors survived in regions of atrophy, but with greatly reduced and highly variable density. Regular arrays of cones were found in some locations, despite abnormal retinal pigment epithelium. For some subjects, the cone density was significantly greater than normative values in some retinal locations outside the atrophy.
   The survival of cones within atrophy is remarkable. The unusually dense packing of cones at some retinal locations outside the atrophy indicates more fluidity in cone distribution than typically thought. Together these findings suggest strategies for therapy that includes preserving cones.
C1 [Elsner, Ann E.] Indiana Univ, Sch Optometry, Bloomington, IN 47405 USA.
   [Papay, Joel A.; Johnston, Kirby D.; Sawides, Lucie; de Castro, Alberto; King, Brett J.; Jones, Durand W.; Clark, Christopher A.; Gast, Thomas J.; Burns, Stephen A.] Indiana Univ, Bloomington, IN USA.
C3 Indiana University System; Indiana University Bloomington; Indiana
   University System; Indiana University Bloomington
RP Elsner, AE (通讯作者)，Indiana Univ, Sch Optometry, Bloomington, IN 47405 USA.
EM aeelsner@indiana.edu
RI de Castro, Alberto/A-7691-2017; Burns, Stephen A/D-9259-2011; Burns,
   Stephen/AAN-3044-2021; Sawides, Lucie/O-1431-2016
OI de Castro, Alberto/0000-0002-2873-3412; Burns, Stephen
   A/0000-0001-5348-035X; Sawides, Lucie/0000-0002-8918-8753; Elsner,
   Ann/0000-0002-9040-9672; King, Brett/0000-0003-4790-3541; Papay,
   Joel/0000-0002-9930-4754
FU NIH NEI [EY07624, EY04395, EY024315, EY024186, EY01867, EY030829]
FX This work was supported by NIH NEI EY07624, EY04395, EY024315, EY024186,
   EY01867, and EY030829.
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NR 103
TC 4
Z9 4
U1 0
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-5408
EI 1475-1313
J9 OPHTHAL PHYSL OPT
JI Ophthalmic Physiol. Opt.
PD MAR
PY 2020
VL 40
IS 2
SI SI
BP 88
EP 116
DI 10.1111/opo.12670
EA FEB 2020
PG 29
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KW1KZ
UT WOS:000510702400001
PM 32017191
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU George, PP
   Yun, OCS
   Siow, K
   Saxena, N
   Heng, BH
   Car, J
   Lockwood, C
AF George, Pradeep Paul
   Yun, Olivia Chng Shih
   Siow, Kalin
   Saxena, Nakul
   Heng, Bee Hoon
   Car, Josip
   Lockwood, Craig
TI Is there scope for expanding the optometrist's scope of practice in
   Singapore? - A survey of optometrists, opticians in Singapore
SO CONTACT LENS & ANTERIOR EYE
LA English
DT Article
DE Extended scope practice; Optometrists; Opticians; Primary eye care;
   Survey; Singapore
AB Purpose: In Singapore, optometrists' roles are limited compared to their counterparts elsewhere. The purpose of the survey is to investigate optometrists' current roles, views on extended roles, self-reported primary eye care knowledge, needs for continuing professional education (CPE) and views on suitable modes for CPE.
   Methods: Members of the Optometrist and Optician Board (OOB) were invited via email to take part in an anonymous online survey. The survey questions covered the following areas: current scope of practice, self-rated primary eye care knowledge, confidence in screening, co-managing minor eye conditions, CPE and referral behavior.
   Results: A total of 230 optometrists completed the survey (response rate 30%). Their current roles were limited to diagnostic refraction (92%), colour vision assessment (65%), contact lens fitting and dispensing (62%) amongst others. The average self-rated score for primary eye care knowledge was 8.2 +/- 1.4; score range 1-10 (1-Very poor, 10-Excellent). Self-rated confidence scores for screening for cataract, diabetic retinopathy, chronic glaucoma and age-related macular degeneration were 2.7 +/- 1.5, 3.7 +/- 1.9, 4.0 +/- 1.9 and 3.8 +/- 1.8, respectively. 71% of the optometrists felt that they should undertake regular CPE to improve their primary eye care knowledge. Blended learning (eLearning and traditional face-to-face lectures) (46.1%) was the most preferred mode for CPE delivery.
   Conclusion: Optometrists in Singapore represent a skilled underutilized primary eye care provider. Though their self-reported primary eye care knowledge is high, their confidence in screening and co-managing chronic eye conditions is low. Enabling them for extended primary eye care role would require further training.
   Significance: Singapore ageing population has led to greater eye care demands. Task-shifting from ophthalmologists to optometrists has been proposed in the literature to handle this growing care demands. At this juncture, this study provides evidence based answers to issues revolving around optometrists' readiness for a role expansion in Singapore.
C1 [George, Pradeep Paul; Saxena, Nakul; Heng, Bee Hoon] HSOR, Natl Healthcare Grp, Singapore, Singapore.
   [Yun, Olivia Chng Shih] Tan Tock Seng Hosp, Optometry Serv, Singapore, Singapore.
   [Siow, Kalin] Singapore Natl Eye Ctr, Optometry Serv, Singapore, Singapore.
   [Car, Josip] Nanyang Technol Univ, Lee Kong Chian Sch Med, Ctr Populat Hlth Sci CePHaS, Singapore, Singapore.
   [Lockwood, Craig] Univ Adelaide, Implementat Sci, Adelaide, SA, Australia.
   [George, Pradeep Paul] Nanyang Technol Univ, Fac Publ Hlth & Epidemiol, Lee Kong Chian Sch Med, Singapore, Singapore.
   [George, Pradeep Paul] Univ Adelaide, Fac Hlth Sci, Adelaide, SA, Australia.
C3 Tan Tock Seng Hospital; Singapore National Eye Center; Nanyang
   Technological University & National Institute of Education (NIE)
   Singapore; Nanyang Technological University; University of Adelaide;
   Nanyang Technological University & National Institute of Education (NIE)
   Singapore; Nanyang Technological University; University of Adelaide
RP George, PP (通讯作者)，Natl Healthcare Grp, 3 Fusionopolis Link,03-08 Nexusone North, Singapore 138543, Singapore.
EM Pradeep_Paul_Gunapal@nhg.com.sg
RI Car, Josip/H-6755-2015; George, Pradeep Paul/ABE-9925-2020
OI Car, Josip/0000-0001-8969-371X; George, Pradeep Paul/0000-0003-4743-1425
FU National Healthcare Group, Singapore
FX This research was a part of PPG's doctoral work and he gratefully
   acknowledges the funding received towards his PhD from the National
   Healthcare Group, Singapore.
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NR 25
TC 4
Z9 4
U1 0
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1367-0484
EI 1476-5411
J9 CONTACT LENS ANTERIO
JI Contact Lens Anterior Eye
PD JUN
PY 2019
VL 42
IS 3
BP 258
EP 264
DI 10.1016/j.clae.2019.02.008
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HW7MH
UT WOS:000466873300005
PM 30819628
DA 2022-11-30
ER

PT J
AU Lin, TW
   Chien, Y
   Lin, YY
   Wang, ML
   Yarmishyn, AA
   Yang, YP
   Hwang, DK
   Peng, CH
   Hsu, CC
   Chen, SJ
   Chien, KH
AF Lin, Tzu-Wei
   Chien, Yueh
   Lin, Yi-Ying
   Wang, Mong-Lien
   Yarmishyn, Aliaksandr A.
   Yang, Yi-Ping
   Hwang, De-Kuang
   Peng, Chi-Hsien
   Hsu, Chih-Chien
   Chen, Shih-Jen
   Chien, Ke-Hung
TI Establishing Liposome-Immobilized Dexamethasone-Releasing PDMS Membrane
   for the Cultivation of Retinal Pigment Epithelial Cells and Suppression
   of Neovascularization
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration (AMD); retinal pigment epithelial (RPE)
   cells; vascular endothelial growth factor (VEGF); polydimethylsiloxane
   (PDMS); induced pluripotent stem cells (iPSCs)
ID THERAPY; COMBINATION; EXPRESSION; VEGF
AB Age-related macular degeneration (AMD) is the eye disease with the highest epidemic incidence, and has great impact on the aged population. Wet-type AMD commonly has the feature of neovascularization, which destroys the normal retinal structure and visual function. So far, effective therapy options for rescuing visual function in advanced AMD patients are highly limited, especially in wet-type AMD, in which the retinal pigmented epithelium and Bruch's membrane structure (RPE-BM) are destroyed by abnormal angiogenesis. Anti-VEGF treatment is an effective remedy for the latter type of AMD; however, it is not a curative therapy. Therefore, reconstruction of the complex structure of RPE-BM and controlled release of angiogenesis inhibitors are strongly required for sustained therapy. The major purpose of this study was to develop a dual function biomimetic material, which could mimic the RPE-BM structure and ensure slow release of angiogenesis inhibitor as a novel therapeutic strategy for wet AMD. We herein utilized plasma-modified polydimethylsiloxane (PDMS) sheet to create a biomimetic scaffold mimicking subretinal BM. This dual-surface biomimetic scaffold was coated with laminin and dexamethasone-loaded liposomes. The top surface of PDMS was covalently grafted with laminin and used for cultivation of the retinal pigment epithelial cells differentiated from human induced pluripotent stem cells (hiPSC-RPE). To reach the objective of inhibiting angiogenesis required for treatment of wet AMD, the bottom surface of modified PDMS membrane was further loaded with dexamethasone-containing liposomes via biotin-streptavidin linkage. We demonstrated that hiPSC-RPE cells could proliferate, express normal RPE-specific genes and maintain their phenotype on laminin-coated PDMS membrane, including phagocytosis ability, and secretion of anti-angiogenesis factor PEDF. By using in vitro HUVEC angiogenesis assay, we showed that application of our membrane could suppress oxidative stress-induced angiogenesis, which was manifested in decreased secretion of VEGF by RPE cells and suppression of vascularization. In conclusion, we propose modified biomimetic material for dual delivery of RPE cells and liposome-enveloped dexamethasone, which can be potentially applied for AMD therapy.
C1 [Lin, Tzu-Wei; Chien, Yueh; Wang, Mong-Lien; Yarmishyn, Aliaksandr A.; Yang, Yi-Ping] Taipei Vet Gen Hosp, Dept Med Res, Taipei 11217, Taiwan.
   [Chien, Yueh; Lin, Yi-Ying; Chien, Ke-Hung] Natl Yang Ming Univ, Sch Med, Inst Pharmacol, Taipei 11217, Taiwan.
   [Wang, Mong-Lien; Chen, Shih-Jen] Natl Yang Ming Univ, Sch Med, Facil Med, Taipei 11217, Taiwan.
   [Hwang, De-Kuang; Peng, Chi-Hsien; Chen, Shih-Jen] Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei 11217, Taiwan.
   [Hwang, De-Kuang] Natl Yang Ming Univ, Dept Publ Hlth, Taipei 11217, Taiwan.
   [Hwang, De-Kuang] Natl Yang Ming Univ, Inst Publ Hlth, Taipei 11217, Taiwan.
   [Peng, Chi-Hsien] Shin Kong Wu Ho Su Mem Hosp, Dept Ophthalmol, Taipei 11101, Taiwan.
   [Peng, Chi-Hsien] Fu Jen Catholic Univ, Taipei 11101, Taiwan.
   [Hsu, Chih-Chien] Natl Yang Ming Univ, Inst Clin Med, Taipei 11217, Taiwan.
   [Chien, Ke-Hung] Triserv Gen Hosp, Dept Ophthalmol, Taipei 11490, Taiwan.
   [Chien, Ke-Hung] Natl Def Med Ctr, Taipei 11490, Taiwan.
C3 Taipei Veterans General Hospital; National Yang Ming Chiao Tung
   University; National Yang Ming Chiao Tung University; Taipei Veterans
   General Hospital; National Yang Ming Chiao Tung University; National
   Yang Ming Chiao Tung University; Shin Kong Wu Ho Su Memorial Hospital;
   Fu Jen Catholic University; National Yang Ming Chiao Tung University;
   Tri-Service General Hospital; National Defense Medical Center
RP Chien, KH (通讯作者)，Natl Yang Ming Univ, Sch Med, Inst Pharmacol, Taipei 11217, Taiwan.; Chien, KH (通讯作者)，Triserv Gen Hosp, Dept Ophthalmol, Taipei 11490, Taiwan.; Chien, KH (通讯作者)，Natl Def Med Ctr, Taipei 11490, Taiwan.
EM backyard0826@gmail.com; g39005005@gmail.com; s19609005@gm.ym.edu.tw;
   monglien@gmail.com; yarmishyn@gmail.com; molly0103@gmail.com;
   m95gbk@hotmail.com; chpeng1008@gmail.com; chihchienym@gmail.com;
   sjchen96@gmail.com; yred8530@gmail.com
RI Hwang, DK De-Kuang/J-3931-2016
OI Hwang, DK De-Kuang/0000-0001-6346-8485; Hsu,
   Chih-Chien/0000-0003-2354-2999
FU Novel Bioengineering and Technological Approaches to Solve Two Major
   Health Problems in Taiwan - Taiwan Ministry of Science and Technology
   Academic Excellence Program [MOST 106-2633-B-009-001, MOST
   107-2633-B-009-003]; Ministry of Science and Technology [MOST
   106-2319-B-001-003, MOST 107-2319-B-001-003, MOST 106-2119-M-010-001,
   MOST 107-2119-M-010-001, MOST 107-2320-B-010-023, MOST
   106-3114-B-010-002, MOST 107-2321-B-010-007]; Academia Sinica
   [106-0210-01-15-02, 107-0210-01-19-01]; Taipei Veterans General Hospital
   [V106E-004-2, V106C-001, V107C-139, V107E-002-2]; TSGH [TSGH-C108-122];
   NDMC [MAB-108-049]; AS Joint Research Program [VTA107-V1-5-1,
   VTA107-V1-5-2]; TVGH-NTUH Joint Research Program [VN106-02, VN107-16];
   VGHUST Joint Research Program [VGHUST107-G1-6-1]; Department of Health
   Cancer Center Research of Excellence [MOHW106-TDU-B-211-113001,
   MOHW107-TDU-B-211-123001]; National Health Research Institutes, Taiwan
   [NHRI-EX106-10621BI, NHRI-EX107-10621BI]; "Cancer Progression Research
   Center, National Yang-Ming University" from Featured Areas Research
   Center Program by the Ministry of Education (MOE) in Taiwan; Ministry of
   Education through SPROUT Project-Center for Intelligent Drug Systems and
   Smart Bio-devices (IDS2B) of National Chiao Tung University, Taiwan
FX This research was funded in part by the Novel Bioengineering and
   Technological Approaches to Solve Two Major Health Problems in Taiwan
   sponsored by the Taiwan Ministry of Science and Technology Academic
   Excellence Program (MOST 106-2633-B-009-001, MOST 107-2633-B-009-003).
   Ministry of Science and Technology (MOST 106-2319-B-001-003, MOST
   107-2319-B-001-003, MOST 106-2119-M-010-001, MOST 107-2119-M-010-001,
   MOST 107-2320-B-010-023, MOST 106-3114-B-010-002. MOST
   107-2321-B-010-007), Academia Sinica (106-0210-01-15-02,
   107-0210-01-19-01), Taipei Veterans General Hospital (V106E-004-2,
   V106C-001, V107C-139 and V107E-002-2), TSGH (TSGH-C108-122), NDMC
   (MAB-108-049), AS Joint Research Program (VTA107-V1-5-1, VTA107-V1-5-2),
   TVGH-NTUH Joint Research Program (VN106-02 and VN107-16), VGHUST Joint
   Research Program (VGHUST107-G1-6-1), The Department of Health Cancer
   Center Research of Excellence (MOHW106-TDU-B-211-113001 and
   MOHW107-TDU-B-211-123001), National Health Research Institutes
   (NHRI-EX106-10621BI and NHRI-EX107-10621BI), Taiwan. This work was
   financially supported by the "Cancer Progression Research Center,
   National Yang-Ming University" from The Featured Areas Research Center
   Program within the framework of the Higher Education Sprout Project by
   the Ministry of Education (MOE) in Taiwan. This paper (work) is
   particularly supported by the Ministry of Education through the SPROUT
   Project-Center for Intelligent Drug Systems and Smart Bio-devices
   (IDS2B) of National Chiao Tung University, Taiwan.
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NR 30
TC 5
Z9 6
U1 2
U2 6
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD JAN 2
PY 2019
VL 20
IS 2
AR 241
DI 10.3390/ijms20020241
PG 17
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA HM8QS
UT WOS:000459746500009
PM 30634448
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Pezzullo, L
   Streatfeild, J
   Simkiss, P
   Shickle, D
AF Pezzullo, Lynne
   Streatfeild, Jared
   Simkiss, Philippa
   Shickle, Darren
TI The economic impact of sight loss and blindness in the UK adult
   population
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
DE Sight loss; Blindness; Visual impairment; Cost-of-illness; Health
   economics; Cost analysis; United Kingdom
ID AGED 75 YEARS; VISUAL IMPAIRMENT; UNITED-STATES; OLDER-PEOPLE;
   DISABILITY WEIGHTS; GLOBAL BURDEN; EYE DISEASE; MRC TRIAL; ADD-ON;
   PREVALENCE
AB Background: To quantify the economic impact of sight loss and blindness in the United Kingdom (UK) population, including direct and indirect costs, and its burden on health.
   Methods: Prevalence data on sight loss and blindness by condition, Census demographic data, data on indirect costs, and healthcare cost databases were used. Blindness was defined as best corrected visual acuity (BCVA) of < 6/60, and sight loss as BCVA < 6/12 to 6/60, in the better-seeing eye.
   Results: Sight loss and blindness from age-related macular degeneration (AMD), cataract, diabetic retinopathy, glaucoma and under-corrected refractive error are estimated to affect 1.93 (1.58 to 2.31) million people in the UK. Direct health care system costs were 3.0 pound billion, with inpatient and day care costs comprising 735 pound million (24.6%) and outpatient costs comprising 771 pound million (25.8%). Indirect costs amounted to 5.65 pound (5.12 to 6.22) billion. The value of the loss of healthy life associated with sight loss and blindness was estimated to be 19.5 pound (15.9 to 23.3) billion or 7.2 pound (5.9 to 8.6) billion, depending on the set of disability weights used. For comparison with other published results using 2004 disability weights and the 2008 estimates, the total economic cost of sight loss and blindness was estimated to be 28.1 pound (24.0 to 32.5) billion in 2013. Using 2010 disability weights, the estimated economic cost of sight loss and blindness was estimated to be 15.8 pound (13.5 to 18.3) billion in 2013.
   Conclusions: The large prevalence of sight loss and blindness in the UK population imposes significant costs on public funds, private expenditure, and health. Prevalence estimates relied on dated epidemiological studies and may not capture recent advances in treatment, highlighting the need for population-based studies that track the prevalence of sight-impairing eye conditions and treatment effects over time.
C1 [Pezzullo, Lynne; Streatfeild, Jared] Deloitte Access Econ Pty Ltd, 8 Brindabella Circuit, Canberra Airport, ACT 2609, Australia.
   [Simkiss, Philippa] Royal Natl Inst Blind People, London, England.
   [Shickle, Darren] Univ Leeds, Leeds Inst Hlth Sci, London, England.
C3 Deloitte Touche Tohmatsu Limited; University of Leeds
RP Streatfeild, J (通讯作者)，Deloitte Access Econ Pty Ltd, 8 Brindabella Circuit, Canberra Airport, ACT 2609, Australia.
EM jstreatfeild@deloitte.com.au
FU Royal National Institute of Blind People; Novartis Pharmaceuticals UK
   Ltd.
FX This research was supported by the Royal National Institute of Blind
   People and Novartis Pharmaceuticals UK Ltd. RNIB engaged LP and JS to
   design the study and undertake the analysis. Novartis Pharmaceuticals UK
   Ltd. provided an educational grant to RNIB for this purpose. Novartis
   Pharmaceuticals UK Ltd. had no role in the analysis, interpretation or
   preparation of the manuscript.
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NR 88
TC 60
Z9 60
U1 1
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD JAN 30
PY 2018
VL 18
AR 63
DI 10.1186/s12913-018-2836-0
PG 13
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Health Care Sciences & Services
GA FU4IH
UT WOS:000423816200012
PM 29382329
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Prager, P
   Hollborn, M
   Steffen, A
   Wiedemann, P
   Kohen, L
   Bringmann, A
AF Prager, Philipp
   Hollborn, Margrit
   Steffen, Anja
   Wiedemann, Peter
   Kohen, Leon
   Bringmann, Andreas
TI P2Y(1) Receptor Signaling Contributes to High Salt-Induced Priming of
   the NLRP3 Inflammasome in Retinal Pigment Epithelial Cells
SO PLoS One
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; PATHOGENIC T(H)17 CELLS; AGE-RELATED
   MACULOPATHY; MACULAR DEGENERATION; BLOOD-PRESSURE; ARPE-19 CELLS;
   ACTIVATION; INDUCTION; INHIBITORS; SODIUM
AB Background
   Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine purinergic (P2) receptor signaling contributes to the NaCI-induced NLRP3 gene expression.
   Methodology/Principal Findings
   Hyperosmolarity was induced by the addition of 100 mM NaCl or sucrose to the culture medium. Gene and protein expression levels were determined with real-time RT-PCR and Western blot analysis, respectively. IL-1 beta and IL-18 levels were evaluated with ELISA. Nuclear factor of activated T cell 5 (NFAT5) expression was knocked down with siRNA. High extracellular NaCI induced NLRP3 and pro-IL-1 beta gene expression, while the gene expression of further inflammasome-associated proteins (NLRP1, NLRP2, NLRP6, NLRP7, NLRP12, NLRC4, AIM2, ASC, procaspase-1, pro-IL-18) was not altered or below the detection threshold. The NaCI-induced NLRP3 gene expression was partially dependent on the activities of phospholipase C, IP3 receptors, protein kinase C, the serum and glucocorticoid-regulated kinase, p38 MAPK, ERK1/2, JNK, P13K, and the transcription factors HIF-1 and NFAT5. Pannexin-dependent ATP release and P2Y(1) receptor activation is required for the full induction of NLRP3 gene expression. High NaCI induced a transient increase of the NLRP3 protein level and a moderate NLRP3 inflammasome activation, as indicated by the transient increase of the cytosolic level of mature IL-1 beta. High NaCl also induced secretion of IL-18.
   Conclusion
   High extracellular NaCl induces priming of the NLRP3 inflammasome in RPE cells, in part via P2Y(1) receptor signaling. The inflammasome priming effect of NaCl suggests that high intake of dietary salt may promote local retinal inflammation implicated in the development of AMD.
C1 [Prager, Philipp; Hollborn, Margrit; Steffen, Anja; Wiedemann, Peter; Kohen, Leon; Bringmann, Andreas] Univ Leipzig, Dept Ophthalmol, Leipzig, Germany.
   [Prager, Philipp; Hollborn, Margrit; Steffen, Anja; Wiedemann, Peter; Kohen, Leon; Bringmann, Andreas] Univ Leipzig, Hosp Eye, Leipzig, Germany.
   [Kohen, Leon] Helios Klinikum Aue, Aue, Germany.
C3 Leipzig University; Leipzig University; Helios Kliniken
RP Bringmann, A (通讯作者)，Univ Leipzig, Dept Ophthalmol, Leipzig, Germany.; Bringmann, A (通讯作者)，Univ Leipzig, Hosp Eye, Leipzig, Germany.
EM bria@medizin.uni-leipzig.de
FU Deutsche Forschungsgemeinschaft [KO 1547/7-1]; Geschwister Freter
   Stiftung (Hannover, Germany)
FX Supported by grants from the Deutsche Forschungsgemeinschaft (KO
   1547/7-1 to L.K.) and the Geschwister Freter Stiftung (Hannover,
   Germany).
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NR 49
TC 29
Z9 30
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 27
PY 2016
VL 11
IS 10
AR e0165653
DI 10.1371/journal.pone.0165653
PG 20
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EE4VY
UT WOS:000389604900119
PM 27788256
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Stefano, JE
   Bird, J
   Kyazike, J
   Cheng, AWM
   Boudanova, E
   Dwyer, M
   Hou, LH
   Qiu, HW
   Matthews, G
   O'Callaghan, M
   Pan, CQ
AF Stefano, James E.
   Bird, Julie
   Kyazike, Josephine
   Cheng, Anthony Wai-Ming
   Boudanova, Ekaterina
   Dwyer, Markryan
   Hou, Lihui
   Qiu, Huawei
   Matthews, Gloria
   O'Callaghan, Michael
   Pan, Clark Q.
TI High-Affinity VEGF Antagonists by Oligomerization of a Minimal Sequence
   VEGF-Binding Domain
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; LIGAND-BINDING;
   ANGIOGENESIS; RECEPTOR; NEOVASCULARIZATION; INHIBITION; MOLECULES;
   VARIANTS; TUMOR
AB Vascular endothelial growth factor (VEGF) neutralizing antagonists including antibodies or receptor extracellular domain Pc fusions have been applied clinically to control angiogenesis in cancer, wet age-related macular degeneration, and edema. We report here the generation of high-affinity VEGF-binding domains by chemical linkage of the second domain of the VEGF receptor Flt-1 (D2) in several configurations. Recombinant D2 was expressed with a 13 a.a. C-terminal tag, including a C-terminal cysteine to enable its dimerization by disulfide bond formation or by attachment to divalent PEGs and oligomerization by coupling to multivalent PEGs. Disulfide-linked dimers produced by Cu2+ oxidation of the free-thiol form of the protein demonstrated picomolar affinity for VEGF in solution, comparable to that of a D2-Fc fusion (sFLT01) and similar to 50-fold higher than monomeric D2, suggesting the 26 a.a. tag length between the two D2 domains permits simultaneous interaction of both faces of the VEGF homodimer. Extending the separation between the D2 domains by short PEG spacers from 0.35 kD to 5 kD produced a modest, similar to 2-fold increase in affinity over the disulfide, thus defining the optimal distance between the two D2 domains for maximum affinity. By surface plasmon resonance (SPR), a larger (similar to 5-fold) increase in affinity was observed by conjugation of the D2 monomer to the termini of 4-arm PEG, and yielding a product with a larger hydrodynamic radius than sFLT01. The higher affinity displayed by these D2 PEG tetramers than either D2 dimer or sFLT01 was largely a consequence of a slower rate of dissociation, suggesting the simultaneous binding by these tetramers to neighboring surface-bound VEGF. Finally, disulfide-linked D2 dimers showed a greater resistance to autocatalytic fragmentation than sFLT01 under elevated temperature stress, indicating such minimum-sequence constructs may be better suited for sustained-release formulations. Therefore, these constructs represent novel Fc-independent VEGF antagonists with ultrahigh affinity, high stability, and a range of hydrodynamic radii for application to multiple therapeutic targets.
C1 [Stefano, James E.; Bird, Julie; Kyazike, Josephine; Boudanova, Ekaterina; Hou, Lihui; Qiu, Huawei; Pan, Clark Q.] Genzyme Corp, Prot Engn, Framingham, MA 01701 USA.
   [Matthews, Gloria] Genzyme Corp, Preclin Orthopaed, Framingham, MA 01701 USA.
   [Dwyer, Markryan] Genzyme Corp, New Biol, Framingham, MA 01701 USA.
   [Cheng, Anthony Wai-Ming] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
   [O'Callaghan, Michael] 4s3Bioscience Inc, Medford, MA USA.
C3 Sanofi-Aventis; Genzyme Corporation; Sanofi-Aventis; Genzyme
   Corporation; Sanofi-Aventis; Genzyme Corporation; Duke University
RP Stefano, JE (通讯作者)，Genzyme Corp, Prot Engn, Framingham, MA 01701 USA.
EM jstefano@genzyme.com
OI Jaworski, Julie/0000-0002-0633-287X; Stefano, James/0000-0003-1024-0836
FU Osteoarthritis Research Society International
FX This study was in part supported by a scholarship to A.W.M.C. from the
   Osteoarthritis Research Society International. We would like to thank
   Dan Li and Jon Kingsbury for useful discussions and Bob Mattaliano for a
   critical reading of the manuscript.
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NR 23
TC 6
Z9 9
U1 0
U2 24
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD DEC
PY 2012
VL 23
IS 12
BP 2354
EP 2364
DI 10.1021/bc300301m
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Chemistry, Multidisciplinary; Chemistry, Organic
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 055PW
UT WOS:000312429900005
PM 23176598
DA 2022-11-30
ER

PT J
AU Coassin, M
   Duncan, KG
   Bailey, KR
   Singh, A
   Schwartz, DM
AF Coassin, Marco
   Duncan, Keith G.
   Bailey, Kathy R.
   Singh, Ajay
   Schwartz, Daniel M.
TI Hypothermia reduces secretion of vascular endothelial growth factor by
   cultured retinal pigment epithelial cells
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID FACTOR GENE-EXPRESSION; LOCAL HYPOTHERMIA; MILD HYPOTHERMIA; MODERATE
   HYPOTHERMIA; PATHOPHYSIOLOGICAL PROBLEMS; INTRAVITREAL BEVACIZUMAB;
   THERAPEUTIC HYPOTHERMIA; METABOLIC REDUCTION; OXIDATIVE STRESS; MACULAR
   EDEMA
AB Aim Visual loss in age-related macular degeneration usually develops secondary to choroidal neovascularisation. Vascular endothelial growth factor (VEGF) is a critical regulator of retinal angiogenesis and vascular permeability, especially in hypoxic conditions. We hypothesise that hypothermia may reduce the retinal pigment epithelium (RPE) metabolism and, consequently, the levels of VEGF secretion by cultured RPE cells under hypoxic conditions. The effects of hypothermia were compared with the metabolic inhibiting effects of thiopental and nicotinamide.
   Methods ARPE-19 cells were grown in culture for up to 5 days under normoxic (20% O-2) and hypoxic (1% O-2) conditions at temperatures ranging from 27 degrees C to 40 degrees C. For experiments with pharmacological agents, thiopental and nicotinamide were added to the media. VEGF levels in the media were measured by ELISA and cell metabolic activity was measured by a fluorescent cell metabolic assay.
   Results We found that hypothermia reduced ARPE-19 cell metabolism in a temperature-dependent fashion. Hypothermia also reduced ARPE-19 cell VEGF secretion in a temperature-dependent fashion. ARPE-19 cell VEGF secretion was reduced by 38% at 34 degrees C compared with cells grown at 37 degrees C. Conversely, ARPE-19 cell VEGF secretion was increased by 32% at 40 degrees C compared with cells grown at 37 degrees C. Hypoxia increased ARPE-19 cell VEGF secretion by 84% at 37 degrees C. However, hypothermia decreased the hypoxia-induced increase of ARPE-19 cell VEGF secretion by 30%. The effect of hypothermia on ARPE-19 cell VEGF secretion was reversible after 4 days. In contrast to hypothermia, thiopental and nicotinamide were able to reduce RPE cell metabolism but not VEGF secretion.
   Conclusion Hypothermia decreases both VEGF secretion and cellular metabolism in ARPE-19 cells. Hypothermia also mitigates the hypoxia-induced increase in ARPE-19 cell VEGF secretion. These effects of hypothermia are potentially unique and cannot be obtained by other pharmacological agents that slow cellular metabolism.
C1 [Coassin, Marco; Duncan, Keith G.; Bailey, Kathy R.; Singh, Ajay; Schwartz, Daniel M.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
   [Schwartz, Daniel M.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
C3 University of California System; University of California San Francisco;
   US Department of Veterans Affairs; Veterans Health Administration (VHA)
RP Schwartz, DM (通讯作者)，Univ Calif San Francisco, Dept Ophthalmol, 10 Koret Way,Room 320, San Francisco, CA 94143 USA.
EM schwartz7@mindspring.com
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NR 71
TC 21
Z9 21
U1 0
U2 7
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD DEC
PY 2010
VL 94
IS 12
BP 1678
EP 1683
DI 10.1136/bjo.2009.168864
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 683IJ
UT WOS:000284469000026
PM 20805126
DA 2022-11-30
ER

PT J
AU Fujihara, M
   Nagai, N
   Sussan, TE
   Biswal, S
   Handa, JT
AF Fujihara, Masashi
   Nagai, Norihiro
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   Biswal, Shyam
   Handa, James T.
TI Chronic Cigarette Smoke Causes Oxidative Damage and Apoptosis to Retinal
   Pigmented Epithelial Cells in Mice
SO PLOS ONE
LA English
DT Article
AB The purpose of this study was to determine whether mice exposed to chronic cigarette smoke develop features of early age-related macular degeneration (AMD). Two month old C57Bl6 mice were exposed to either filtered air or cigarette smoke in a smoking chamber for 5 h/day, 5 days/week for 6 months. Eyes were fixed in 2.5% glutaraldehyde/2% paraformaldehyde and examined for ultrastructural changes by transmission electron microscopy. The contralateral eye was fixed in 2% paraformaldehyde and examined for oxidative injury to the retinal pigmented epithelium (RPE) by 8-oxo-7,8-dihydro-29-deoxyguanosine (8-OHdG) immunolabeling and apoptosis by TUNEL labeling. Mice exposed to cigarette smoke had immunolabeling for 8-OHdG in 85 +/- 63.7% of RPE cells counted compared to 9.5 +/- 63.9% in controls (p < 0.00001). Bruch membrane was thicker in mice exposed to smoke (1086 +/- 332 nm) than those raised in air (543 +/- 132 nm; p = 0.0069). The two most pronounced ultrastructural changes (severity grading scale from 0- 3) seen were a loss of basal infoldings (mean difference in grade = 1.98; p < 0.0001), and an increase in intracellular vacuoles (mean difference in grade = 1.7; p < 0.0001). Ultrastructural changes to Bruch membrane in cigarette-smoke exposed mice were smaller in magnitude but consistently demonstrated significantly higher grade injury in cigarette- exposed mice, including basal laminar deposits (mean difference in grade = 0.54; p, 0.0001), increased outer collagenous layer deposits (mean difference in grade = 0.59; p = 0.002), and increased basal laminar deposit continuity (mean difference in grade = 0.4; p, 0.0001). TUNEL assay showed a higher percentage of apoptotic RPE from mice exposed to cigarette smoke (average 8.0 +/- 1.1%) than room air (average 0 +/- 0%; p = 0.043). Mice exposed to chronic cigarette smoke develop evidence of oxidative damage with ultrastructural degeneration to the RPE and Bruch membrane, and RPE cell apoptosis. This model could be useful for studying the mechanism of smoke induced changes during early AMD.
C1 [Fujihara, Masashi; Nagai, Norihiro; Handa, James T.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
   [Sussan, Thomas E.; Biswal, Shyam] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins
   University; Johns Hopkins Bloomberg School of Public Health
RP Fujihara, M (通讯作者)，Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
EM jthanda@jhmi.edu
OI Sussan, Thomas/0000-0002-5240-4299
FU QLT, Inc; NIH [EY14005, HL081205]; Thomas Orton Jones Fellowship in
   Age-related Macular Degeneration; NIH/NHLBI SCCOR [P50HL084945]; Flight
   Attendant Medical Research Institute; NIEHS [ES07141]; Wilmer Eye
   Institute [EY01765]; NATIONAL EYE INSTITUTE [R01EY014005, P30EY001765]
   Funding Source: NIH RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
   [R01HL081205, P50HL084945] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [T32ES007141] Funding Source:
   NIH RePORTER
FX This work was supported by a grant from QLT, Inc., NIH EY14005 to JTH;
   Thomas Orton Jones Fellowship in Age-related Macular Degeneration (JTH);
   NIH HL081205, NIH/NHLBI SCCOR grant P50HL084945, research grant from
   Flight Attendant Medical Research Institute to SB. TES is supported by
   the NIEHS training grant ES07141; EY01765 (Microscopy Module Core Grant)
   and Research to Prevent Blindness to the Wilmer Eye Institute; and
   generous gifts from Ric and Sandy Forsythe, the Kwok family, the Merlau
   family, and Aleda Wright. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 46
TC 114
Z9 118
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 1
PY 2008
VL 3
IS 9
AR e3119
DI 10.1371/journal.pone.0003119
PG 7
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 422GW
UT WOS:000264416600007
PM 18769672
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Arias, L
   Garcia-Arumi, J
   Ramon, JM
   Badia, M
   Rubio, M
   Pujol, O
AF Arias, L.
   Garcia-Arumi, J.
   Ramon, J. M.
   Badia, M.
   Rubio, M.
   Pujol, O.
TI Optical coherence tomography analysis of a randomized study combining
   photodynamic therapy with intravitreal triamcinolone
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE optical coherence tomography; intravitreal triamcinolone; photodynamic
   therapy; choroidal neovascularization; age-related macular degeneration
ID CHOROIDAL NEOVASCULARIZATION; FLUORESCEIN ANGIOGRAPHY
AB Background The objective of the study was to analyze optical coherence tomography (OCT) scan differences between patients with predominantly classic subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with only photodynamic therapy (PDT) and patients treated with PDT combined with intravitreal triamcinolone acetonide (IVTA).
   Methods In this prospective study, 61 patients were randomized to receive PDT (n=30) or PDT combined with IVTA (n=31). They were evaluated every 3 months with a refraction protocol for best-corrected visual acuity (VA) measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, fluorescein angiography (FA), and OCT. When measuring foveal thickness on OCT scans, neuroretinal foveal thickness (NFT) was differentiated from outer high reflectivity band thickness (OHRBT). The main outcome measures were mean change in OCT measurements and correlation of VA and angiographic area of the lesion with OCT measurements.
   Results At the 12-month follow-up, the mean change in NFT was not significantly reduced (P=0.9), but the mean change in OHRBT was significantly lower (P=0.004) in the group of patients who received combined therapy. There was no correlation between final VA and NFT in either patient group (P=0.2). The final VA was significantly worse in eyes with a thicker OHRBT (P=0.04) in the group of patients treated with only PDT. There was no correlation between angiographic area and NFT and OHRBT in either patient group (P > 0.3). There was a statistically significant difference between the pre-treatment angiographic area of the lesion and VA at the 12-month follow-up in the combined therapy group (P=0.01), and more eyes treated with only PDT presented with intraretinal fluid at the last follow-up (P=0.01).
   Conclusion Combined PDT+IVTA therapy was more effective than PDT alone at reducing OHRBT. This OCT measurement seems to be have a greater effect on VA than NFT.
C1 [Arias, L.; Rubio, M.; Pujol, O.] Bellvitge Univ Hosp, Dept Ophthalmol, Barcelona 08907, Spain.
   [Arias, L.; Garcia-Arumi, J.] Univ Autonoma Barcelona, Valle Hebron Univ Hosp, Dept Ophthalmol, E-08193 Barcelona, Spain.
   [Garcia-Arumi, J.] IMO, Barcelona, Spain.
   [Ramon, J. M.] Bellvitge Univ Hosp, Dept Prevent Med, Barcelona, Spain.
   [Badia, M.] Bellvitge Univ Hosp, Dept Pharm, Barcelona, Spain.
C3 Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Bellvitge
   University Hospital; University of Barcelona; Autonomous University of
   Barcelona; Hospital Universitari Vall d'Hebron; Institut d'Investigacio
   Biomedica de Bellvitge (IDIBELL); Bellvitge University Hospital;
   University of Barcelona; Institut d'Investigacio Biomedica de Bellvitge
   (IDIBELL); Bellvitge University Hospital; University of Barcelona
RP Arias, L (通讯作者)，Bellvitge Univ Hosp, Dept Ophthalmol, C Feixa Llarga,S-N Hosp Llobregat, Barcelona 08907, Spain.
EM luisarias@telefonica.net
RI Rubio Caso, Marcos Javier/L-6866-2013
OI Rubio Caso, Marcos Javier/0000-0002-7072-9855; ARIAS,
   LUIS/0000-0001-7041-5576; Garcia-Arumi, Jose/0000-0001-8827-1160
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NR 22
TC 3
Z9 3
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD FEB
PY 2008
VL 246
IS 2
BP 245
EP 254
DI 10.1007/s00417-007-0642-1
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 252SU
UT WOS:000252467700013
PM 17674020
DA 2022-11-30
ER

PT J
AU Chen, M
   Forrester, JV
   Xu, HP
AF Chen, Mei
   Forrester, John V.
   Xu, Heping
TI Synthesis of complement factor H by retinal pigment epithelial cells is
   down-regulated by oxidized photoreceptor outer segments
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE complement; complement factor H; age-related macular degeneration;
   retinal pigment epithelial cells; photoreceptor outer segment; cytokine
ID C-REACTIVE PROTEIN; MACULAR DEGENERATION; LIPOFUSCIN ACCUMULATION;
   PATHOGENESIS; INTERLEUKIN-6; INFLAMMATION; POLYMORPHISM; MEMBRANES;
   DRUSEN; RISK
AB Complement activation is thought to be involved in the pathogenesis of age-related macular degeneration (AMD), in part because certain gene polymorphisms in complement factor H (CFH), an important regulator of the alternative complement activation pathway, are high risk factors for AMD. How CFH is regulated locally at the retina/choroid interface and how this contributes to AMD development remain unknown. In the present study, we have confirmed that CFH was detectable by immunohistochemistry in the choroid, and at low levels in the RPE cell and interphotoreceptor matrix, but appeared to be concentrated in dense patches in Bruch's membrane. In vitro, cultured human and mouse RPE cells expressed high levels of CFH as evidenced by immunohistochemistry and western blot. Using a stabilized mouse RPE cell line, we confirmed that RPE cells constitutively synthesise CFH. Synthesis of CFH was not affected by a short-term (2 h) photoreceptor outer segment (POS) treatment. However, long-term (24-48 h) treatment of RPE cells with oxidised POS (ox-POS) but not normal POS (n-POS) markedly down-regulated CFH mRNA expression. Phagocytosis of both ox-POS and n-POS appeared to reduce intracellular CFH protein expression in RPE cultures. Synthesis of CFH by cultured RPE cells was also reduced at the mRNA level by the proinflammatory cytokines TNF-alpha and IL-6. Other cytokines tested including IFN-gamma, IL-1 alpha and IL-4 showed no effect on either CFH protein or mRNA levels. Our results support the view that RPE cells synthesise and express CFH and are probably a major local source of this protein at the retina/choroid interface, secreting CFH into the interphotoreceptor matrix as well as Bruch's membrane. Prolonged phagocytosis of POS, particularly if modified by oxidative processes as occurs in inflammation, appears to markedly impair synthesis and secretion of CFH, with potential loss of important regulatory functions in counteracting the pro-inflammatory effects of activated complement. (c) 2006 Elsevier Ltd. All rights reserved.
C1 Univ Aberdeen, Sch Med, Inst Med Sci, Dept Ophthalmol, Aberdeen AB25 2ZD, Scotland.
C3 University of Aberdeen
RP Xu, HP (通讯作者)，Univ Aberdeen, Sch Med, Inst Med Sci, Dept Ophthalmol, Foresterhill, Aberdeen AB25 2ZD, Scotland.
EM h.xu@abdn.ac.uk
RI Xu, Heping/A-4430-2008; Mohammed, Imran/J-8271-2012
OI Xu, Heping/0000-0003-4000-931X; Mohammed, Imran/0000-0002-8412-0768
CR Anderson DH, 2004, EXP EYE RES, V78, P243, DOI 10.1016/j.exer.2003.10.011
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NR 37
TC 143
Z9 152
U1 0
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD APR
PY 2007
VL 84
IS 4
BP 635
EP 645
DI 10.1016/j.exer.2006.11.015
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 158VC
UT WOS:000245822200005
PM 17292886
DA 2022-11-30
ER

PT J
AU Schutt, F
   Fischer, J
   Kopitz, J
   Holz, FG
AF Schutt, F
   Fischer, J
   Kopitz, J
   Holz, FG
TI Indocyanine green angiography in the presence of subretinal or
   intraretinal haemorrhages: clinical and experimental investigations
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE choroidal neovascularization; fluorescein angio-graphy; haemorrhage;
   indocyanine green angiography
ID OCCULT CHOROIDAL NEOVASCULARIZATION; SCANNING LASER OPHTHALMOSCOPE;
   MACULAR DEGENERATION; VIDEOANGIOGRAPHY
AB Purpose: The absorption and emission characteristics of indocyanine green are associated with better penetration through ocular pigments, including melanin and blood, in comparison with fluorescein. Therefore, it has been assumed that indocyanine green angiography (ICG-A) allows better delineation of fluorescent structures including choroidal neovascularization in the presence of haemorrhages. The degree and frequency of blockage by haemorrhages during ICG-A and fluorescein angiography (Fl-A) were compared and absorption characteristics by blood were experimentally determined.
   Methods: Simultaneous confocal scanning laser ophthalmo-scopy was performed in patients with intraretinal or sub-retinal haemorrhages associated with various retinal diseases including neovascular age-related macular degeneration. Areas of blocked choroidal fluorescence were compared in Fl-A and ICG-A using a standardized classification system by two independent readers. Experimental absorption measurements were performed using blood-filled quartz cuvettes and laser light with 488 and 790 nm, respectively.
   Results: Sixty eyes of 59 patients were analysed. Twelve eyes (20%) showed blockage in Fl-A only corresponding with funduscopically visible blood. In 35 eyes (58%) the extent of absorption was greater in Fl-A compared with ICG-A. An identical area of blockage in both Fl-A and ICG-A was noted in 13 eyes (22%). The coefficient of absorption was 18.4 mm(-1) for Fl-A (488 nm) and 5.4 mm(-1) for ICG-A (790 nm).
   Conclusions: In contrast to previous assumptions, the findings indicate that clinically intraretinal or subretinal haemorrhages are frequently associated with blockage not only in Fl-A but also in ICG-A. This is in accordance with the experimentally determined coefficient of absorption. Apparently, haemorrhages occurring in association with retinal and choroidal diseases commonly have a thickness sufficient enough to induce relevant absorption during ICG-A, and thus impair delineation of fluorescent structures in planes posterior to the haemorrhage. Therefore, the diagnostic value of ICG-A in presence of subretinal or intra-retinal bleedings is limited.
C1 Univ Heidelberg, Dept Ophthalmol, D-69120 Heidelberg, Germany.
   Univ Heidelberg, Inst Appl Phys, D-69120 Heidelberg, Germany.
   Univ Heidelberg, Inst Pathol, D-69120 Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg; Ruprecht Karls University
   Heidelberg; Ruprecht Karls University Heidelberg
RP Holz, FG (通讯作者)，Univ Heidelberg, Dept Ophthalmol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
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NR 26
TC 18
Z9 19
U1 1
U2 4
PU BLACKWELL PUBLISHING ASIA
PI CARLTON
PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA
SN 1442-6404
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD APR
PY 2002
VL 30
IS 2
BP 110
EP 114
DI 10.1046/j.1442-6404.2002.00494.x
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 532KX
UT WOS:000174475000009
PM 11886414
DA 2022-11-30
ER

PT J
AU Parodi, MB
   Arrigo, A
   Bandello, F
AF Parodi, Maurizio Battaglia
   Arrigo, Alessandro
   Bandello, Francesco
TI Optical Coherence Tomography Angiography Quantitative Assessment of
   Macular Neovascularization in Best Vitelliform Macular Dystrophy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE Best vitelliform macular dystrophy; macular neovascularization; optical
   coherence tomography angiography
ID CHOROIDAL NEOVASCULARIZATION; FUNDUS AUTOFLUORESCENCE; PATTERNS
AB PURPOSE. To describe quantitative characteristics of macular neovascularization (MNV) in vitelliform macular dystrophy (VMD) patients by means of optical coherence tomography angiography (OCTA).
   METHODS. The study design was a prospective case series. All patients underwent complete ophthalmologic assessment, optical coherence tomography, and OCTA. The quantitative OCTA parameters examined included vessel tortuosity and vessel dispersion of the MNV. The primary outcome was OCTA characterization of MNV in VMD. Secondary outcomes included the evolution of MNV over the follow-up.
   RESULTS. A total of 78 eyes were recruited for the study. MNV was identified in 50 eyes (64%) at baseline and in 51 eyes (65%) at the end of the follow-up (mean follow-up, 24.7 +/- 9.7 months). MNV was detected in four out of the 30 eyes classified as stages 2 and 3 (13%), showing exudative manifestations and undergoing ranibizumab treatment, leading to clinical stabilization. OCTA detected MNV in 46 out of 48 eyes (96%) classified as stages 4 and 5, showing no evidence of exudative manifestation. All of the non-exudative MNVs were merely observed over the follow-up and received no treatment. At the end of the follow-up, 47 out of 48 eyes displayed MNV (98%). Non-exudative MNVs remained stable over the follow-up. Statistically significant differences were found when comparing vessel tortuosity and vessel dispersion in the two MNV subforms.
   CONCLLS1ONS. VMD is characterized by two MNV subforms. Exudative MNV is rare and may develop in the early stages of the disease, in association with bleeding and fluid formation. Non-exudative MNV develops very commonly in the advanced stage of VMD, without any exudative manifestation.
C1 [Parodi, Maurizio Battaglia; Arrigo, Alessandro; Bandello, Francesco] Univ Vita Salute San Raffaele, Osped San Raffaele, IRCCS, Dept Ophthalmol, Milan, Italy.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele
RP Arrigo, A (通讯作者)，Univ Vita Salute, Osped San Raffaele, Dept Ophthalmol, Via Olgettina 60, I-20132 Milan, Italy.
EM alessandro.arrigo@hotmail.com
OI bandello, francesco/0000-0003-3238-9682; Battaglia Parodi,
   Maurizio/0000-0002-0385-7961
CR Adler P., 2013, POROUS MEDIA GEOMETR
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NR 29
TC 7
Z9 7
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2020
VL 61
IS 6
AR 61
DI 10.1167/iovs.61.6.61
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MD7MJ
UT WOS:000544154500061
PM 32602906
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Koh, AEH
   Alsaeedi, HA
   Abd Rashid, MB
   Lam, CS
   Harun, MHN
   Ng, MH
   Isa, HM
   Then, KY
   Bastion, MLC
   Farhana, A
   Alam, MK
   Subbiah, SK
   Mok, PL
AF Koh, Avin Ee-Hwan
   Alsaeedi, Hiba Amer
   Abd Rashid, Munirah Binti
   Lam, Chenshen
   Harun, Mohd Hairul Nizam
   Ng, Min Hwei
   Mohd Isa, Hazlita
   Then, Kong Yong
   Bastion, Mae-Lynn Catherine
   Farhana, Aisha
   Khursheed Alam, Mohammad
   Subbiah, Suresh Kumar
   Mok, Pooi Ling
TI Transplanted Erythropoietin-Expressing Mesenchymal Stem Cells Promote
   Pro-survival Gene Expression and Protect Photoreceptors From Sodium
   Iodate-Induced Cytotoxicity in a Retinal Degeneration Model
SO FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE mesenchymal stem cells; erythropoietin; sodium iodate; transcriptome;
   photoreceptors; pro-survival genes
AB Mesenchymal stem cells (MSC) are highly regarded as a potential treatment for retinal degenerative disorders like retinitis pigmentosa and age-related macular degeneration. However, donor cell heterogeneity and inconsistent protocols for transplantation have led to varied outcomes in clinical trials. We previously showed that genetically-modifying MSCs to express erythropoietin (MSCEPO) improved its regenerative capabilities in vitro. Hence, in this study, we sought to prove its potential in vivo by transplanting MSCsEPO in a rat retinal degeneration model and analyzing its retinal transcriptome using RNA-Seq. Firstly, MSCsEPO were cultured and expanded before being intravitreally transplanted into the sodium iodate-induced model. After the procedure, electroretinography (ERG) was performed bi-weekly for 30 days. Histological analyses were performed after the ERG assessment. The retina was then harvested for RNA extraction. After mRNA-enrichment and library preparation, paired-end RNA-Seq was performed. Salmon and DESeq2 were used to process the output files. The generated dataset was then analyzed using over-representation (ORA), functional enrichment (GSEA), and pathway topology analysis tools (SPIA) to identify enrichment of key pathways in the experimental groups. The results showed that the MSCEPO-treated group had detectable ERG waves (P <0.05), which were indicative of successful phototransduction. The stem cells were also successfully detected by immunohistochemistry 30 days after intravitreal transplantation. An initial over-representation analysis revealed a snapshot of immune-related pathways in all the groups but was mainly overexpressed in the MSC group. A subsequent GSEA and SPIA analysis later revealed enrichment in a large number of biological processes including phototransduction, regeneration, and cell death (P-adj <0.05). Based on these pathways, a set of pro-survival gene expressions were extracted and tabulated. This study provided an in-depth transcriptomic analysis on the MSCEPO-treated retinal degeneration model as well as a profile of pro-survival genes that can be used as candidates for further genetic enhancement studies on stem cells.
C1 [Koh, Avin Ee-Hwan; Alsaeedi, Hiba Amer; Mok, Pooi Ling] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Biomed Sci, Serdang, Malaysia.
   [Abd Rashid, Munirah Binti; Lam, Chenshen; Harun, Mohd Hairul Nizam; Mohd Isa, Hazlita; Then, Kong Yong; Bastion, Mae-Lynn Catherine] Univ Kebangsaan Malaysia, Med Ctr, Dept Ophthalmol, Kuala Lumpur, Malaysia.
   [Ng, Min Hwei] Univ Kebangsaan Malaysia, Med Ctr, Tissue Engn Ctr, Kuala Lumpur, Malaysia.
   [Farhana, Aisha; Mok, Pooi Ling] Jouf Univ, Coll Appl Med Sci, Dept Clin Lab Sci, Sakaka, Saudi Arabia.
   [Khursheed Alam, Mohammad] Jouf Univ, Coll Dent, Dept Orthodont, Sakaka, Saudi Arabia.
   [Subbiah, Suresh Kumar] Univ Putra Malaysia, Dept Med Microbiol & Parasitol, Serdang, Malaysia.
   [Subbiah, Suresh Kumar; Mok, Pooi Ling] Univ Putra Malaysia, Genet & Regenerat Med Res Grp, Serdang, Malaysia.
   [Subbiah, Suresh Kumar; Mok, Pooi Ling] Bharath Inst Higher Educ & Res, Dept Biotechnol, Chennai, Tamil Nadu, India.
C3 Universiti Putra Malaysia; Universiti Kebangsaan Malaysia; Universiti
   Kebangsaan Malaysia; Al Jouf University; Al Jouf University; Universiti
   Putra Malaysia; Universiti Putra Malaysia; Bharath Institute of Higher
   Education & Research
RP Mok, PL (通讯作者)，Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Biomed Sci, Serdang, Malaysia.; Mok, PL (通讯作者)，Jouf Univ, Coll Appl Med Sci, Dept Clin Lab Sci, Sakaka, Saudi Arabia.; Subbiah, SK (通讯作者)，Univ Putra Malaysia, Dept Med Microbiol & Parasitol, Serdang, Malaysia.; Subbiah, SK; Mok, PL (通讯作者)，Univ Putra Malaysia, Genet & Regenerat Med Res Grp, Serdang, Malaysia.; Subbiah, SK; Mok, PL (通讯作者)，Bharath Inst Higher Educ & Res, Dept Biotechnol, Chennai, Tamil Nadu, India.
EM sureshkudsc@gmail.com; Mpling@ju.edu.sa
RI Mok, Pooi Ling/AAJ-7480-2021; Kumar, suresh S/J-2423-2017; Farhana,
   Aisha/AAR-7356-2020; HARUN, MOHD HAIRUL NIZAM/D-5351-2017
OI Kumar, suresh S/0000-0002-0505-7554; HARUN, MOHD HAIRUL
   NIZAM/0000-0002-2387-9834; Farhana, Aisha/0000-0002-4631-2769
FU Science Fund - Ministry of Science, Technology and Innovation (MOSTI)
   [5450817]; Putra IPS grant - Universiti Putra Malaysia [9503900];
   Deputyship for Research & Innovation, Ministry of Education in Saudi
   Arabia [375213500]
FX This study was supported by the Science Fund (Grant No. 5450817) awarded
   by the Ministry of Science, Technology and Innovation (MOSTI), and the
   Putra IPS grant awarded by Universiti Putra Malaysia (Grant No.
   9503900). The authors also extend their appreciation to the Deputyship
   for Research & Innovation, Ministry of Education in Saudi Arabia for
   funding this research work through the project number 375213500.
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NR 72
TC 2
Z9 2
U1 2
U2 7
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 2296-634X
J9 FRONT CELL DEV BIOL
JI Front. Cell. Dev. Biol.
PD APR 27
PY 2021
VL 9
AR 652017
DI 10.3389/fcell.2021.652017
PG 17
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA RZ9GT
UT WOS:000648907300001
PM 33987180
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Woodard, DR
   Nakahara, E
   Hulleman, JD
AF Woodard, DaNae R.
   Nakahara, Emi
   Hulleman, John D.
TI Clinically-identified C-terminal mutations in fibulin-3 are prone to
   misfolding and destabilization
SO SCIENTIFIC REPORTS
LA English
DT Article
AB Distinct mutations in the secreted extracellular matrix protein, fibulin-3 (F3), have been associated with a number of ocular diseases ranging from primary open angle glaucoma to cuticular age-related macular degeneration to a rare macular dystrophy, Malattia Leventinese (ML). The R345W F3 mutation that causes ML leads to F3 misfolding, inefficient secretion and accumulation at higher intracellular steady state levels in cultured cells. Herein, we determined whether fifteen other clinically-identified F3 mutations also led to similar levels of misfolding and secretion defects, which might provide insight into their potential pathogenicity. Surprisingly, we found that only a single F3 variant, L451F, presented with a significant secretion defect (69.5 +/- 2.4% of wild-type (WT) F3 levels) and a corresponding increase in intracellular levels (226.8 +/- 25.4% of WT F3 levels). Upon follow-up studies, when this conserved residue (L451) was mutated to a charged (Asp or Arg) or bulky (Pro, Trp, Tyr) residue, F3 secretion was also compromised, indicating the importance of small side chains (Leu, Ala, or Gly) at this residue. To uncover potential inherent F3 instability not easily observed under typical culture conditions, we genetically eliminated the sole stabilizing N-linked glycosylation site (N249) from select clinically-identified F3 mutants. This removal exacerbated R345W and L451F secretion defects (19.8 +/- 3.0% and 12.4 +/- 1.2% of WT F3 levels, respectively), but also revealed a previously undiscovered secretion defect in another C-terminal variant, Y397H (42.0 +/- 10.1% of WT F3 levels). Yet, glycan removal did not change the relative secretion of the N-terminal mutants tested (D49A, R140W, I220F). These results highlight the uniqueness and molecular similarities between the R345W and L451F variants and also suggest that previously identified disease-associated mutations (e.g., R140W) are indistinguishable from WT with respect to secretion, hinting that they may lead to disease by an alternative mechanism.
C1 [Woodard, DaNae R.; Nakahara, Emi; Hulleman, John D.] Univ Texas Southwestern Med Ctr Dallas, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
   [Hulleman, John D.] Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical
   Center Dallas; University of Texas System; University of Texas
   Southwestern Medical Center Dallas
RP Hulleman, JD (通讯作者)，Univ Texas Southwestern Med Ctr Dallas, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.; Hulleman, JD (通讯作者)，Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM John.Hulleman@UTSouthwestern.edu
OI Hulleman, John/0000-0001-8149-656X
FU NIH Diversity Supplement [EY027785-03S]; Roger and Dorothy Hirl Research
   Fund; NEI R01 Grant [EY027785]; Research to Prevent Blindness (RPB); NEI
   Visual Science Core grant [P30 EY030413]; RPB
FX DRW is supported by an NIH Diversity Supplement (EY027785-03S). JDH is
   supported by an endowment from the Roger and Dorothy Hirl Research Fund,
   an NEI R01 Grant (EY027785), and a Career Development Award from
   Research to Prevent Blindness (RPB). Additional support was provided by
   an NEI Visual Science Core grant (P30 EY030413) and an unrestricted
   grant from RPB (both to the UT Southwestern Department of
   Ophthalmology).
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NR 50
TC 3
Z9 3
U1 1
U2 2
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 4
PY 2021
VL 11
IS 1
AR 2998
DI 10.1038/s41598-020-79570-x
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA QH1PH
UT WOS:000618048400015
PM 33542268
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Gao, JY
   Cui, JZ
   To, E
   Cao, SJ
   Matsubara, JA
AF Gao, Jiangyuan
   Cui, Jing Z.
   To, Eleanor
   Cao, Sijia
   Matsubara, Joanne A.
TI Evidence for the activation of pyroptotic and apoptotic pathways in RPE
   cells associated with NLRP3 inflammasome in the rodent eye
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium; NLRP3
   inflammasome; Cell death; Amyloid beta
ID MACULAR DEGENERATION; AMYLOID-BETA; GASDERMIN D; DISEASE; DEATH; IL-18;
   DRUSEN; GSDMD
AB Background: Age-related macular degeneration (AMD) is a devastating eye disease causing irreversible vision loss in the elderly. Retinal pigment epithelium (RPE), the primary cell type that is afflicted in AMD, undergoes programmed cell death in the late stages of the disease. However, the exact mechanisms for RPE degeneration in AMD are still unresolved. The prevailing theories consider that each cell death pathway works independently and without regulation of each other. Building upon our previous work in which we induced a short burst of inflammasome activity in vivo, we now investigate the effects of prolonged inflammasome activity on RPE cell death mechanisms in rats. Methods: Long-Evans rats received three intravitreal injections of amyloid beta (A beta), once every 4 days, and were sacrificed at day 14. The vitreous samples were collected to assess the levels of secreted cytokines. The inflammasome activity was evaluated by both immunohistochemistry and western blot The types of RPE cell death mechanisms were determined using specific cell death markers and morphological characterizations. Results: We found robust inflammasome activation evident by enhanced caspase-1 immunoreactivity, augmented NE-kappa B nuclear translocalization, increased IL-1 beta vitreal secretion, and IL-18 protein levels. Moreover, we observed elevated proteolytic cleavage of caspase-3 and gasdermin D, markers for apoptosis and pyroptosis, respectively, in RPE-choroid tissues. There was also a significant reduction in the anti-apoptotic factor, X-linked inhibitor of apoptosis protein, consistent with the overall changes of RPE cells. Morphological analysis showed phenotypic characteristics of pyroptosis including RPE cell swelling. Conclusions: Our data suggest that two cell death pathways, pyroptosis and apoptosis, were activated in RPE cells after exposure to prolonged inflammasome activation, induced by a drusen component, A beta. The involvement of two distinct cell death pathways in RPE sheds light on the potential interplay between these pathways and provides insights on the future development of therapeutic strategies for AMD.
C1 [Gao, Jiangyuan; Cui, Jing Z.; To, Eleanor; Cao, Sijia; Matsubara, Joanne A.] Univ British Columbia, Dept Ophthalmol & Visual Sci, Eye Care Ctr, Fac Med, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada.
C3 University of British Columbia
RP Matsubara, JA (通讯作者)，Univ British Columbia, Dept Ophthalmol & Visual Sci, Eye Care Ctr, Fac Med, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada.
EM jms@mail.ubc.ca
FU Canadian Institutes of Health Research [MOP126195]
FX The study was funded by a Canadian Institutes of Health Research
   operating grant to JAM. (MOP126195). The funding body did not
   participate in the design of the study, collection, analysis, and
   interpretation of data, and writing the manuscript in any forms.
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NR 45
TC 47
Z9 51
U1 0
U2 9
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD JAN 12
PY 2018
VL 15
AR 15
DI 10.1186/s12974-018-1062-3
PG 12
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA FS6QH
UT WOS:000419921400004
PM 29329580
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Moran, R
   Nolan, JM
   Stack, J
   O'Halloran, AM
   Feeney, J
   Akuffo, KO
   Kenny, RA
   Beatty, S
AF Moran, R.
   Nolan, J. M.
   Stack, J.
   O'Halloran, A. M.
   Feeney, J.
   Akuffo, K. O.
   Kenny, R. A.
   Beatty, S.
TI Non-dietary correlates and determinants of plasma lutein and zeaxanthin
   concentrations in the Irish population
SO JOURNAL OF NUTRITION HEALTH & AGING
LA English
DT Article
DE Lutein; zeaxanthin; ageing; nutrition; lifestyle
ID PIGMENT OPTICAL-DENSITY; AGE-RELATED MACULOPATHY; SERUM CAROTENOID
   CONCENTRATIONS; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH;
   MACULAR PIGMENT; VISUAL IMPAIRMENT; RISK-FACTORS; CONSTITUENT
   CAROTENOIDS; TISSUE CONCENTRATIONS
AB To investigate non-dietary correlates and determinants of plasma lutein (L) and zeaxanthin (Z) concentrations in The Irish Longitudinal Study on Ageing (TILDA) sample.
   Community dwelling adults in the Republic of Ireland (ROI). Participants: 3,681 participants aged 50 years and older.
   TILDA is a nationally representative prospective cohort study of community dwelling adults aged 50 years and over in the ROI. Demographic and health variables were collected during a face-to-face interview carried out in the home (n=8175), and a substantial proportion of these (n=5035; 62%) also attended a study visit in a health assessment centre. Blood samples collected at baseline (wave 1, the subject of the current study), were analysed for plasma concentrations of L and Z by reversed-phase high performance liquid chromatography, and macular pigment (MP) optical density was also measured (using customized heterochromatic flicker photometry).
   After excluding participants with eye disease, data from 3,681 participants were available for analysis. For this group of participants, plasma L and Z were inversely and significantly associated with body mass index (BMI), and were positively and significantly associated with MP, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) (p < 0.001, for all). Plasma L and Z were significantly lower in males, current smokers, participants reporting less physical exercise, and participants reporting lower levels of education (p < 0.05, for all). Plasma L was significantly higher in participants reporting a family history of age-related macular degeneration (AMD) (p=0.001), and in the group of ae<yen>75 years old (p < 0.05). For each of these variables, the significant associations remained after controlling for other potential confounding variables.
   The findings of this large study indicate that plasma concentrations of L and Z were lower in association with indicators of a poor lifestyle (high BMI, tobacco use, and less physical exercise) and in association with lower education, indicating that modifying lifestyle in a positive way is likely to be reflected in higher concentrations of plasma carotenoids, with consequential and putative health benefits.
C1 [Moran, R.; Nolan, J. M.; Stack, J.; Akuffo, K. O.; Beatty, S.] Waterford Inst Technol, Sch Hlth Sci, Macular Pigment Res Grp, Nutr Res Ctr Ireland, Waterford, Ireland.
   [O'Halloran, A. M.; Feeney, J.; Kenny, R. A.] Trinity Coll Dublin, Dept Med Gerontol, Irish Longitudinal Study Ageing, Dublin, Ireland.
   [Feeney, J.] Queens Univ, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
C3 South East Technological University (SETU); Trinity College Dublin;
   Queens University Belfast
RP Moran, R (通讯作者)，Waterford Inst Technol, Nutr Res Ctr Ireland, Macular Pigment Res Grp, West Campus, Carriganore, Waterford, Ireland.
EM rmoran@wit.ie
RI Akuffo, Kwadwo Owusu/J-2036-2019; Nolan, John/N-4921-2014
OI Akuffo, Kwadwo Owusu/0000-0001-6683-249X; O'Halloran,
   Aisling/0000-0001-5498-4453; Feeney, Joanne/0000-0001-9872-2025; Nolan,
   John/0000-0002-5503-7084; Kenny, Rose Anne/0000-0002-9336-8124
FU Bayer, Ireland; Waterford Institute of Technology Presidential
   Scholarship; An Roinn Slainte (Irish Department of Health); Atlantic
   Philanthropies; Irish Life plc; European Research Council (ERC); Centre
   for Ageing Development and Research in Ireland (CARDI)
FX This work was supported by Bayer, Ireland and Waterford Institute of
   Technology Presidential Scholarship. TILDA is funded by An Roinn Slainte
   (Irish Department of Health), The Atlantic Philanthropies, and Irish
   Life plc. J.M. Nolan and K.O. Akuffo are funded by the European Research
   Council (ERC). A.M. O'Halloran and J. Feeney are funded by the Centre
   for Ageing Development and Research in Ireland (CARDI).
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NR 75
TC 10
Z9 10
U1 0
U2 7
PU SPRINGER FRANCE
PI PARIS
PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE
SN 1279-7707
EI 1760-4788
J9 J NUTR HEALTH AGING
JI J. Nutr. Health Aging
PD MAR
PY 2017
VL 21
IS 3
BP 254
EP 261
DI 10.1007/s12603-016-0729-7
PG 8
WC Geriatrics & Gerontology; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Nutrition & Dietetics
GA EN7SS
UT WOS:000396203100004
PM 28244563
DA 2022-11-30
ER

PT J
AU Wang, HB
   Han, XK
   Gambhir, D
   Becker, S
   Kunz, E
   Liu, AJ
   Hartnett, ME
AF Wang, Haibo
   Han, Xiaokun
   Gambhir, Deeksha
   Becker, Silke
   Kunz, Eric
   Liu, Angelina Jingtong
   Hartnett, M. Elizabeth
TI Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model
   of Choroidal Neovascularization
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; INTRAVITREAL
   NEOVASCULARIZATION; MULLER CELLS; RAT MODEL; VEGF; RETINOPATHY;
   MIGRATION; NEURONS
AB Inhibition of chemokine C-C motif receptor 3 (CCR3) signaling has been considered as treatment for neovascular age-related macular degeneration (AMD). However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs) that develop into choroidal neovascularization (CNV). In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Muller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i) significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i-or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF) was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF). In cultured human Muller cells exposed to eotaxin (CCL11) and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2) in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3 inhibition is considered as a therapy for neovascular AMD.
C1 [Wang, Haibo; Han, Xiaokun; Gambhir, Deeksha; Becker, Silke; Kunz, Eric; Liu, Angelina Jingtong; Hartnett, M. Elizabeth] Univ Utah, John A Moran Eye Ctr, Salt Lake City, UT USA.
   [Han, Xiaokun] China Med Univ, Affiliated Hosp 4, Dept Ophthalmol, Shenyang 110001, Peoples R China.
C3 Utah System of Higher Education; University of Utah; China Medical
   University
RP Hartnett, ME (通讯作者)，Univ Utah, John A Moran Eye Ctr, Salt Lake City, UT USA.
EM ME.Hartnett@hsc.utah.edu
RI Chopra, Deeksha Gambhir/K-7148-2014
OI Chopra, Deeksha Gambhir/0000-0003-0835-4703
FU National Eye Institute [R01EY015130, R01EY017011]; March of Dimes
   [6-FY13-75]; Knights Templar Eye Foundation; NATIONAL EYE INSTITUTE
   [R01EY017011] Funding Source: NIH RePORTER
FX This work was supported by the National Eye Institute, R01EY015130 and
   R01EY017011 (https://nei.nih.gov) to MEH, the March of Dimes, 6-FY13-75
   (http://www.marchofdimes.org) to MEH and the Knights Templar Eye
   Foundation (http://www.knightstemplar.org/ktef) to HW. The funders had
   no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
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NR 28
TC 9
Z9 10
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 16
PY 2016
VL 11
IS 6
AR e0157748
DI 10.1371/journal.pone.0157748
PG 16
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DO8JO
UT WOS:000378029800131
PM 27309355
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Anand, A
   Sharma, K
   Sharma, SK
   Singh, R
   Sharma, NK
   Prasad, K
AF Anand, Akshay
   Sharma, Kaushal
   Sharma, Suresh K.
   Singh, Ramandeep
   Sharma, Neel K.
   Prasad, Keshava
TI AMD Genetics in India: The Missing Links
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Review
DE age related macular degeneration; SNP; biomarkers; longitudinal
   analysis; snSNPs; bio-informatics analysis; statistical modeling;
   Mendelian randomization
ID RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL-GROWTH-FACTOR; TOLL-LIKE
   RECEPTOR-3; AMYOTROPHIC-LATERAL-SCLEROSIS; GENOME-WIDE ASSOCIATION;
   COMPLEMENT FACTOR-H; BODY-MASS INDEX; MACULAR DEGENERATION; MENDELIAN
   RANDOMIZATION; MESSENGER-RNA
AB Age related macular degeneration is a disease which occurs in aged individuals. There are various changes that occur, at the cellular, molecular and physiological level with advancing age (Sarniec et al., 1988; Sharma K. et al., 2014). Drusen deposition between retinal pigment epithelium (RPE) and Bruch's membrane (BM) is one of the key features in AMD patients (Mullins et al., 2000: Hageman et al., 2001) similar to Artau aggregates in Alzheimer's disease (AD) patients. The primary goal of this review is to discuss whether the various candidate genes and associated biomarkers, that are known to play an independent role in progression of AMD, exert deleterious effect on phenotype, alone or in combination, in Indian AMD patients from the same ethnic group and the significance of such research. A statistical model for probable interaction between genes could be derived from such analysis. Therefore, one can use multiple modalities to identify and enrol AMD patients based on established clinical criteria and examine the risk factors to determine if these genes are associated with risk factors, biomarkers or disease by Mendelian randomization. Similarly, there are large numbers of single nucleotide polymorphisms (SNPs) identified in human population. Even non-synonymous SNPs (nsSNPs) are believed to induce deleterious effects on the functionality of various proteins. The study of such snSNPs could provide a better genetic insight for diverse phenotypes of AMD patients, predicting significant risk factors for the disease in Indian population. Therefore, the prediction of biological effect of nsSNPs in the candidate genes and the associated grant applications in the subject are highly solicited.Therefore, genotyping and levels of protein expression of various genes would provide wider canvas in genetic complexity of AMD pathology which should be evaluated by valid statistical and bioinformatics' tools. Longitudinal follow up of Indian AMD patients to evaluate the temporal effect of SNPs and biomarkers on progression of disease would provide a unique strategy in the field.
C1 [Anand, Akshay; Sharma, Kaushal] Postgrad Inst Med Educ & Res, Neurosci Res Lab, Dept Neurol, Chandigarh 160012, India.
   [Sharma, Kaushal; Sharma, Suresh K.] Panjab Univ, Ctr Syst Biol & Bioinformat, Chandigarh 160014, India.
   [Sharma, Suresh K.] Panjab Univ, Dept Stat, Chandigarh 160014, India.
   [Singh, Ramandeep] Postgrad Inst Med Educ & Res, Adv Eye Ctr, Chandigarh 160012, India.
   [Sharma, Neel K.] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA.
   [Prasad, Keshava] Inst Bioinformat, Bangalore, Karnataka, India.
   [Prasad, Keshava] Yenepoya Univ, YU IOB Ctr Syst Biol & Mol Med, Mangalore, India.
   [Prasad, Keshava] Natl Inst Mental Hlth & Neurosci, NIMHANS IOB Prote & Bioinformat Lab, Neurobiol Res Ctr, Bangalore 560029, Karnataka, India.
C3 Post Graduate Institute of Medical Education & Research (PGIMER),
   Chandigarh; Panjab University; Panjab University; Post Graduate
   Institute of Medical Education & Research (PGIMER), Chandigarh; National
   Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI);
   Yenepoya (Deemed to be University); National Institute of Mental Health
   & Neurosciences - India
RP Anand, A (通讯作者)，Postgrad Inst Med Educ & Res, Neurosci Res Lab, Dept Neurol, Chandigarh 160012, India.
EM akshay1anand@rediffmail.com
RI Prasad, Keshava/F-7631-2010
OI Prasad, Keshava/0000-0002-6206-2384
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NR 81
TC 5
Z9 5
U1 0
U2 12
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
   SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD MAY 23
PY 2016
VL 8
AR 115
DI 10.3389/fnagi.2016.00115
PG 14
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DM6QP
UT WOS:000376477800001
PM 27252648
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Yin, VT
   Weisbrod, DJ
   Eng, KT
   Schwartz, CE
   Kohly, R
   Mandelcorn, E
   Lam, WC
   Daneman, N
   Simor, A
   Kertes, PJ
AF Yin, Vivian T.
   Weisbrod, Daniel J.
   Eng, Kenneth T.
   Schwartz, Carol E.
   Kohly, Radha
   Mandelcorn, Efrem
   Lam, Wai-Ching
   Daneman, Nick
   Simor, Andrew
   Kertes, Peter J.
TI Antibiotic Resistance of Ocular Surface Flora With Repeated Use of a
   Topical Antibiotic After Intravitreal Injection
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID POVIDONE-IODINE; FLUOROQUINOLONE RESISTANCE; ANTIMICROBIAL RESISTANCE;
   MACULAR DEGENERATION; CHEMICAL PREPARATION; BACTERIAL KERATITIS;
   CAUSATIVE ORGANISMS; OPHTHALMIC SURGERY; CATARACT-SURGERY; DRUG
   INJECTION
AB Importance: Treatment with intravitreal (IVT) injections has increased during the last several years as evidence has accumulated demonstrating the efficacy of anti-vascular endothelial growth factor agents in the treatment of neovascular age-related macular degeneration (AMD) and various retinal vascular diseases. Although IVT injections are generally safe infectious endophthalmitis is a rare but devastating complication and the risk of morbidity and vision loss from endophthalmitis is high.
   Objective: To examine the change in antibiotic resistance of ocular surface flora with repeated prophylactic use of antibiotics after IVT injection for AMD.
   Design and Setting: Prospective nonrandomized cohort study in 2 tertiary academic hospitals.
   Participants: Patients 65 years and older with newly diagnosed AMD were recruited by 7 retinal specialists from July 1, 2010, through December 31, 2011.
   Intervention: The study group received topical moxifloxacin hydrochloride for 3 days after each monthly IVT injection.
   Main Outcome Measure: Resistance to moxifloxacin and ceftazidime in cultured isolates at baseline and monthly for 3 months by change in minimal inhibitory concentration (MIC) of culture isolates was studied.
   Results: The study group consisted of 84 patients and the control group had 94 patients. In the study group the baseline adjusted MIC increased (from 1.04 to 1.25 mu g/mL; P=.01) as did the MIC for 50% of isolates (MIC50) (from 0.64 to 1.00 mu g/mL) and the MIC for 90% of isolates(MIC90) (from 0.94 to 4.00 mu g/mL). In both groups the culture-positive rate did not change significantly when adjusted for baseline. No significant change was found in the MIC level culture-positive rate MIC50 level and MIC90 level in the control group. Subgroup analysis found diabetes mellitus to be noncontributory to both the MIC and culture-positive rate. No endophthalmitis or adverse events were reported.
   Conclusions and Relevance: Repeated use of topical moxifloxacin after IVT injection significantly increases antibiotic resistance of ocular surface flora. We recommend that routine use of prophylactic
C1 [Daneman, Nick; Simor, Andrew] Sunnybrook Hlth Sci Ctr, Dept Med, Toronto, ON M4N 3M5, Canada.
   [Daneman, Nick; Simor, Andrew] Sunnybrook Hlth Sci Ctr, Dept Microbiol, Toronto, ON M4N 3M5, Canada.
   [Mandelcorn, Efrem; Lam, Wai-Ching; Kertes, Peter J.] Univ Hlth Network, Toronto Western Hosp, Donald K Johnson Eye Ctr, Dept Ophthalmol & Vis Sci, Toronto, ON, Canada.
   [Weisbrod, Daniel J.; Eng, Kenneth T.; Schwartz, Carol E.; Kohly, Radha] Univ Toronto, Toronto, ON, Canada.
C3 University of Toronto; Sunnybrook Research Institute; University Toronto
   Affiliates; Sunnybrook Health Science Center; University of Toronto;
   Sunnybrook Research Institute; University Toronto Affiliates; Sunnybrook
   Health Science Center; University of Toronto; University Toronto
   Affiliates; University Health Network Toronto; University of Toronto
RP Kertes, PJ (通讯作者)，Sunnybrook Hlth Sci Ctr, Dept Ophthalmol & Vis Sci, John & Liz Tory Eye Ctr, 2075 Bayview Ave,Ste M1-202A, Toronto, ON M4N 3M5, Canada.
EM peter.kertes@sunnybrook.ca
OI Lam, Wai-Ching/0000-0003-2057-9374
FU Physician Services Inc [10Q2140]; Novartis
FX This study was funded by resident research grant 10Q2140 from Physician
   Services Inc and Novartis research grant-in-aid.
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NR 40
TC 77
Z9 81
U1 1
U2 25
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD APR
PY 2013
VL 131
IS 4
BP 456
EP 461
DI 10.1001/jamaophthalmol.2013.2379
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 163JH
UT WOS:000320331600005
PM 23430175
OA Bronze
DA 2022-11-30
ER

PT J
AU Canton, VM
   Quiroz-Mercado, H
   Velez-Montoya, R
   Lopez-Miranda, MJ
   Moshfeghi, AA
   Shusterman, EM
   Kaiser, PK
   Sanislo, SR
   Gertner, M
   Moshfeghi, DM
AF Canton, Virgilio Morales
   Quiroz-Mercado, Hugo
   Velez-Montoya, Raul
   Lopez-Miranda, Miriam J.
   Moshfeghi, Andrew A.
   Shusterman, Eugene M.
   Kaiser, Peter K.
   Sanislo, Steven R.
   Gertner, Michael
   Moshfeghi, Darius M.
TI 16-Gy Low-Voltage X-ray Irradiation With Ranibizumab Therapy for AMD:
   6-Month Safety and Functional Outcomes
SO OPHTHALMIC SURGERY LASERS & IMAGING
LA English
DT Article
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; EXTERNAL-BEAM IRRADIATION;
   MACULAR DEGENERATION; RADIATION RETINOPATHY; PLAQUE RADIOTHERAPY;
   STEREOTACTIC RADIOSURGERY; BRACHYTHERAPY; BEVACIZUMAB; MEMBRANES;
   SECONDARY
AB BACKGROUND AND OBJECTIVE: To describe the 6-month safety and preliminary efficacy outcomes of the use of 16-Gy radiation with intravitreal ranibizumab for patients with neovascular age-related macular degeneration (AMD).
   PATIENTS AND METHODS: A single treatment of a non-invasive, externally delivered low-voltage 16-Gy x-ray irradiation was administered in one session through three locations in the inferior pars plana. Optical coherence tomography (OCT) and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) examinations were performed at 1 week, 1 month, and monthly thereafter, with quarterly fluorescein angiography (FA). After the two initial ranibizumab injections, subsequent injections were administered according to the following criteria: VA decline of 10 ETDRS letters compared with baseline, increase of 100-mu m central foveal thickness on OCT compared with baseline, the development of new submacular hemorrhage, and the development of a new area of classic choroidal neovascularization on FA.
   RESULTS: Twenty-six patients completed a 6-month follow-up. There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean baseline ETDRS score was 46.6 letters (range: 5 to 80; standard deviation [SD]: 21.5). At 6 months, the corresponding ETDRS score was 55.6 letters (range: 25 to 80; SD: 18.9) and the mean change in VA was 9.5 ETDRS letters (SD: 10.3). On responder analysis, 96% lost 15 or fewer ETDRS letters, 81% gained 0 or more ETDRS letters, and 50% gained 15 or more ETDRS letters. Patients received a total of 13 ranibizumab injections following two initial injections. At 6 months, patients received an average of 0.5 additional injections following the initial two mandated injections.
   CONCLUSION: A single treatment of externally applied, non-invasive 16-Gy low-voltage x-ray therapy in conjunction with ranibizumab demonstrated an overall improvement of VA in patients with neovascular AMD at 6 months with no radiation-related adverse effects.
C1 [Sanislo, Steven R.; Moshfeghi, Darius M.] Stanford Univ, Sch Med, Byers Eye Inst, Dept Ophthalmol,Horngren Family Vitreoretinal Ctr, Palo Alto, CA 94303 USA.
   [Canton, Virgilio Morales; Quiroz-Mercado, Hugo; Velez-Montoya, Raul; Lopez-Miranda, Miriam J.] IAP, Assoc Evitar Ceguera Mexico, Mexico City, DF, Mexico.
   [Quiroz-Mercado, Hugo; Velez-Montoya, Raul] Univ Colorado, Dept Ophthalmol, Denver, CO 80202 USA.
   [Moshfeghi, Andrew A.] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Palm Beach Gardens, FL USA.
   [Shusterman, Eugene M.; Gertner, Michael] Oraya Therapeut Inc, Newark, CA USA.
   [Kaiser, Peter K.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.
C3 Stanford University; University of Colorado System; University of
   Colorado Denver; Bascom Palmer Eye Institute; Cleveland Clinic
   Foundation
RP Moshfeghi, DM (通讯作者)，Stanford Univ, Sch Med, Byers Eye Inst Stanford, Dept Ophthalmol,Horngren Family Vitreoretinal Ctr, 2452 Watson Court, Palo Alto, CA 94303 USA.
EM dariusm@stanford.edu
RI Canton, Virgilio/AAF-7047-2021; Velez-Montoya, Raul/K-3819-2015
OI Velez-Montoya, Raul/0000-0002-6457-4578; Moshfeghi, Darius
   Mohammad/0000-0003-2254-292X; Kaiser, Peter/0000-0001-5126-045X
FU Thrombogenics, Inc.
FX Drs. D. Moshfeghi and Kaiser are consultants and have equity, Drs.
   Canton, Quiroz-Mercado, and Sanislo are consultants, Dr. Shusterman is
   an employee and has equity, and Dr. Gertner has equity and intellectual
   property at Oraya Therapeutics, Inc. Dr. A. Moshfeghi is a consultant
   and speaker for Genentech, Inc., Allergan, Inc., and Bausch & Lomb,
   Inc.; is a consultant for Eyetech, Inc., and Alimera, Inc.; and receives
   research funding from Thrombogenics, Inc. Drs. Velez-Montoyo and
   Lopez-Miranda have no financial or proprietary interest in the materials
   presented herein.
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NR 43
TC 13
Z9 14
U1 0
U2 3
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 1542-8877
EI 1938-2375
J9 OPHTHAL SURG LAS IM
JI Ophthalmic Surg. Lasers Imaging
PD NOV-DEC
PY 2011
VL 42
IS 6
BP 468
EP 473
DI 10.3928/15428877-20110804-01
PG 6
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA 959UZ
UT WOS:000305342500004
PM 21830747
DA 2022-11-30
ER

PT J
AU Zhong, XF
   Huang, H
   Shen, JK
   Zacchigna, S
   Zentilin, L
   Giacca, M
   Vinores, SA
AF Zhong, Xiufeng
   Huang, Hu
   Shen, Jikui
   Zacchigna, Serena
   Zentilin, Lorena
   Giacca, Mauro
   Vinores, Stanley A.
TI Vascular endothelial growth factor-B gene transfer exacerbates retinal
   and choroidal neovascularization and vasopermeability without promoting
   inflammation
SO MOLECULAR VISION
LA English
DT Article
ID OXYGEN-INDUCED RETINOPATHY; RECEPTOR TYROSINE KINASES; OUTER PLEXIFORM
   LAYER; VEGF-B; EYE DISEASE; IN-VIVO; PATHOLOGICAL ANGIOGENESIS;
   PERMEABILITY FACTOR; DIABETIC RETINA; AAV SEROTYPES
AB Purpose: The role of vascular endothelial growth factor (VEGF)-B in the eye is poorly understood. The present study was conducted to evaluate the effect of overexpression of VEGF-B via adeno-associated virus (AAV) gene transfer on ocular angiogenesis, inflammation, and the blood-retinal barrier (BRB).
   Methods: Three recombinant AAV vectors were prepared, expressing the 167 (AAV-VEGF-B167) or 186 amino acid isoform (AAV-VEGF-B186) of VEGF-B or the green fluorescent protein (GFP) reporter gene (AAV-GFP). Approximately 1x10(9) viral genome copies of AAV-VEGF-B167, AAV-VEGF-B186, or AAV-GFP were intraocularly injected. The efficacy of the gene transfer was assessed by directly observing GFP, by immunohistochemistry, or by real-time PCR. A leukostasis assay using fluorescein isothiocyanate-conjugated Concanavalin A was used to evaluate inflammation. The BRB was assessed using a quantitative assay with H-3-mannitol as a tracer. Retinal neovascularization (NV) was assessed at postnatal day 17 in oxygen-induced ischemic retinopathy after intravitreal injection of AAV-VEGF-B in left eyes and AAV-GFP in right eyes at postnatal day 7. Two weeks after injection of AAV vectors, choroidal NV was generated by laser photocoagulation and assessed 2 weeks later.
   Results: GFP expression was clearly demonstrated, primarily in the retinal pigment epithelium (RPE) and outer retina, 1-6 weeks after delivery. mRNA expression levels of VEGF-B167 and VEGF-B186 were 5.8 and 12 fold higher in the AAV-VEGF-B167- and AAV-VEGF-B186-treated groups, respectively. There was no evidence of an inflammatory response or vessel abnormality following injection of the vectors in normal mice; however, VEGF-B increased retinal and choroidal neovascularization. AAV-VEGF-B186, but not AAV-VEGF-B167, enhanced retinal vascular permeability.
   Conclusions: VEGF-B overexpression promoted pathological retinal and choroidal NV and BRB breakdown without causing inflammation, which is associated with the progression of diabetic retinopathy and age-related macular degeneration, showing that these complications are not dependent on inflammation. VEGF-B targeting could benefit antiangiogenic therapy.
C1 [Zhong, Xiufeng; Huang, Hu; Shen, Jikui; Vinores, Stanley A.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
   [Zacchigna, Serena; Zentilin, Lorena; Giacca, Mauro] Int Ctr Genet Engn & Biotechnol, Mol Med Lab, I-34012 Trieste, Italy.
C3 Johns Hopkins University; Johns Hopkins Medicine; International Center
   for Genetic Engineering & Biotechnology (ICGEB)
RP Vinores, SA (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, M023 Robert H & Clarice Smith Bldg,400 N Broadway, Baltimore, MD 21287 USA.
EM svinores@jhmi.edu
RI Giacca, Mauro/J-9287-2016; ZACCHIGNA, SERENA/E-9496-2017
OI Giacca, Mauro/0000-0003-2927-7225; ZACCHIGNA, SERENA/0000-0001-6705-3076
FU NIH [EY017164]; National Eye Institute; Wilmer Eye Institute, Johns
   Hopkins Univ.; European Research Council (ERC) [20090506]; NATIONAL EYE
   INSTITUTE [R01EY017164] Funding Source: NIH RePORTER
FX Supported by NIH grant EY017164 from the National Eye Institute, The
   Ronald G. Michels Research Grant Award through the Wilmer Eye Institute,
   Johns Hopkins Univ., and Advanced Grant 20090506 from the European
   Research Council (ERC).
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NR 83
TC 31
Z9 38
U1 0
U2 6
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD FEB 17
PY 2011
VL 17
IS 57-58
BP 492
EP 507
PG 16
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 722AQ
UT WOS:000287401600001
PM 21364963
DA 2022-11-30
ER

PT J
AU Borel, P
   de Edelenyi, FS
   Vincent-Baudry, S
   Malezet-Desmoulin, C
   Margotat, A
   Lyan, B
   Gorrand, JM
   Meunier, N
   Drouault-Holowacz, S
   Bieuvelet, S
AF Borel, Patrick
   de Edelenyi, Fabien Szabo
   Vincent-Baudry, Stephanie
   Malezet-Desmoulin, Christiane
   Margotat, Alain
   Lyan, Bernard
   Gorrand, Jean-Marie
   Meunier, Nathalie
   Drouault-Holowacz, Sophie
   Bieuvelet, Severine
TI Genetic variants in BCMO1 and CD36 are associated with plasma lutein
   concentrations and macular pigment optical density in humans
SO ANNALS OF MEDICINE
LA English
DT Article
DE Age-related macular degeneration; bioavailability; carotenoids; eye;
   genetic polymorphisms; genetic variant; nutrition; retina; xanthophylls
ID B TYPE-I; SCAVENGER RECEPTOR; INTESTINAL-ABSORPTION; VITAMIN-E; SERUM
   CONCENTRATIONS; BETA-CAROTENE; SR-BI; TISSUE CONCENTRATIONS;
   ADIPOSE-TISSUE; FATTY-ACID
AB Lutein is recovered at high concentration in the human macula lutea. Recent studies suggest that this micronutrient might be implicated in prevention of age-related macular degeneration.
   Objective. To identify genes which affect blood and retina lutein concentrations among candidate genes (intestinal sterol transporters and carotenoid oxygenases).
   Design. A comparative plus an observational study.
   Participants. Twenty-nine healthy subjects for the comparative study and 622 subjects for the observational study.
   Intervention and methods. All the participants were genotyped for single nucleotide polymorphisms (SNPs) in the candidate genes. Fasting plasma lutein concentrations were measured in all the participants and after 6 months' supplementation, with either a lutein-rich supplement or a placebo, in the 29 subjects who participated in the comparative study. Macular pigment optical density (MPOD), which is a measure of macula concentration of lutein, was measured before and after the dietary intervention in the 29 subjects. Associations between SNPs and plasma lutein and MPOD were assessed by partial least square (PLS) regression followed by univariate analysis. Observed associations between SNPs and plasma lutein were verified by haplotype-based association analysis in the cohort of 622 subjects.
   Main outcome measures. Plasma lutein levels and MPOD.
   Results. Six SNPs in four genes (ABCG8, BCMO1, CD36, and NPC1L1) explained 25% and 38% of the plasma and MPOD variance, respectively. Subjects with TT at the BCMO1 rs7501331 locus had lower (P < 0.05) plasma lutein than CT subjects. Subjects with CC at the CD36 rs13230419 locus had lower (P < 0.05) plasma lutein than subjects who carried a T allele. The association between CD36 and plasma lutein was confirmed in the cohort of 622 subjects. Subjects with TT at the BCMO1 rs7501331 locus had a higher (P < 0.05) MPOD, and subjects with GG at rs1761667 CD36 locus had a higher (P < 0.05) MPOD than those with an A allele.
   Conclusions. These results suggest that BCMO1 and CD36 are implicated in plasma and retina concentrations of lutein and that genetic variants in these genes can modulate blood and retina concentrations of lutein.
C1 [Borel, Patrick] Fac Med Marseille, UMR 1260, INRA, ERL,INSERM,NLPMM,U1025, F-13385 Marseille 5, France.
   [Borel, Patrick; de Edelenyi, Fabien Szabo; Malezet-Desmoulin, Christiane; Margotat, Alain] INRA, Nutriments Lipid & Prevent Malad Metab UMR1260, F-13385 Marseille, France.
   [Borel, Patrick; de Edelenyi, Fabien Szabo; Malezet-Desmoulin, Christiane; Margotat, Alain] Univ Aix Marseille 2, Univ Aix Marseille 1, F-13385 Marseille, France.
   [Vincent-Baudry, Stephanie; Drouault-Holowacz, Sophie; Bieuvelet, Severine] Pileje, F-75015 Paris, France.
   [Lyan, Bernard; Meunier, Nathalie] Ctr Rech & Nutr Humaine Auvergne, F-63009 Clermont Ferrand, France.
   [Gorrand, Jean-Marie] Fac Pharm Clermont Ferrand, Lab Biophys Sensorielle, F-63001 Clermont Ferrand, France.
C3 INRAE; Institut National de la Sante et de la Recherche Medicale
   (Inserm); UDICE-French Research Universities; Aix-Marseille Universite;
   INRAE; UDICE-French Research Universities; Aix-Marseille Universite; CHU
   Clermont Ferrand
RP Borel, P (通讯作者)，Fac Med Marseille, UMR 1260, INRA, ERL,INSERM,NLPMM,U1025, 27 Blvd Jean Moulin, F-13385 Marseille 5, France.
EM Patrick.Borel@univmed.fr
RI Borel, Patrick/A-4057-2015; Szabo de Edelenyi, Fabien/F-2715-2017
OI Borel, Patrick/0000-0001-9977-3238; Szabo de Edelenyi,
   Fabien/0000-0002-8487-6557; NATHALIE, MEUNIER/0000-0003-3477-4904
FU ANR [ANR-05-PNRA-010]; DGS (Ministry of Health); Mederic; Ipsen; MGEN;
   SODEXHO; Pierre Fabre
FX Work on the cohort of 29 subjects was funded by Pileje. Pileje
   participated in the design of the study and approval of the manuscript.
   Work on the subset cohort of SU.VI.MAX was granted by ANR
   (n<SUP>o</SUP>ANR-05-PNRA-010), DGS (Ministry of Health), and supported
   by Mederic, Ipsen, MGEN, SODEXHO, and Pierre Fabre. None of these
   organizations or companies participated in the design or conducted of
   this research.
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NR 59
TC 70
Z9 71
U1 2
U2 21
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0785-3890
EI 1365-2060
J9 ANN MED
JI Ann. Med.
PD FEB
PY 2011
VL 43
IS 1
BP 47
EP 59
DI 10.3109/07853890.2010.531757
PG 13
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 714RT
UT WOS:000286827400005
PM 21091228
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Bone, RA
   Landrum, JT
   Cao, Y
   Howard, AN
   Alvarez-Calderon, F
AF Bone, Richard A.
   Landrum, John T.
   Cao, Yisi
   Howard, Alan N.
   Alvarez-Calderon, Francesca
TI Macular pigment response to a supplement containing meso-zeaxanthin,
   lutein and zeaxanthin
SO NUTRITION & METABOLISM
LA English
DT Article
ID PLASMA KINETICS; CAROTENOIDS; MEMBRANES; DENSITY; SERUM;
   3'-DEHYDRO-LUTEIN; RETINA; MODEL
AB Background: Age-related macular degeneration ( AMD) is a disease with multiple risk factors, many of which appear to involve oxidative stress. Macular pigment, with its antioxidant and light-screening properties, is thought to be protective against AMD. A result has been the appearance of dietary supplements containing the macular carotenoids, lutein and zeaxanthin. More recently, a supplement has been marketed containing, in addition, the third major carotenoid of the macular pigment, meso-zeaxanthin. The purpose of the study was to determine the effectiveness of such a supplement in raising macular pigment density in human subjects.
   Methods: A 120 day supplementation study was conducted in which 10 subjects were given gel-caps that provided 20 mg/day of predominantly meso-zeaxanthin, with smaller amounts of lutein and zeaxanthin. A second group of 9 subjects were given gel caps containing a placebo for the same 120 day period. Prior to and during the supplementation period, blood serum samples were analyzed by high performance liquid chromatography for carotenoid content. Similarly, macular pigment optical density was measured by heterochromatic flicker photometry. Differences in response between the supplementation and placebo groups were tested for significance using a student's t-test.
   Results: During supplementation with the carotenoids, blood samples revealed the presence of all three carotenoids. Macular pigment optical density, measured at 460 nm, rose at an average rate of 0.59 +/- 0.79 milli-absorbance unit/day in the 10 supplemented subjects. This was significantly different from the placebo group ( 9 subjects) for whom the average rate was -0.17 +/- 0.42 milli-absorbance units/day.
   Conclusion: We have shown for the first time that meso-zeaxanthin is absorbed into the serum following ingestion. The data indicate that a supplement containing predominantly meso-zeaxanthin is generally effective at raising macular pigment density, and may turn out to be a useful addition to the defenses against AMD.
C1 Florida Int Univ, Dept Phys, Miami, FL 33199 USA.
   Florida Int Univ, Dept Chem & Biochem, Miami, FL 33199 USA.
   Univ Cambridge Downing Coll, Cambridge CB2 1DQ, England.
C3 State University System of Florida; Florida International University;
   State University System of Florida; Florida International University;
   University of Cambridge
RP Bone, RA (通讯作者)，Florida Int Univ, Dept Phys, 11200 SW 8th St, Miami, FL 33199 USA.
EM bone@fiu.edu; landrumj@fiu.edu; yisi.cao@fiu.edu;
   howard_foundation@dial.pipex.com; franches20@hotmail.com
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NR 34
TC 72
Z9 79
U1 1
U2 25
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1743-7075
J9 NUTR METAB
JI Nutr. Metab.
PD MAY 11
PY 2007
VL 4
AR 12
DI 10.1186/1743-7075-4-12
PG 8
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 169IO
UT WOS:000246586100001
PM 17498306
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Atmaca-Sonmez, P
   Li, Y
   Yamauchi, Y
   Schanie, CL
   Ildstad, ST
   Kaplan, HJ
   Enzmann, V
AF Atmaca-Sonmez, Pelin
   Li, Yang
   Yamauchi, Yasuyuki
   Schanie, Carrie L.
   Ildstad, Suzanne T.
   Kaplan, Henry J.
   Enzmann, Volker
TI Systemically transferred hematopoietic stem cells home to the subretinal
   space and express RPE-65 in a mouse model of retinal pigment epithelium
   damage
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE RPE degeneration; sodium iodate; stem cells; hematopoietic stem cells;
   transplantation; homing; RPE-65 expression
ID BONE-MARROW; FACILITATING CELLS; REPAIR; MICE; MOBILIZATION; MIGRATION;
   MUSCLE; BLOOD
AB Stem cell regeneration of damaged tissue has recently been reported in many different organs. Since the loss of retinal pigment epithelium (RPE) in the eye is associated with a major cause of visual loss - specifically, age-related macular degeneration - we investigated whether hematopoictic stem cells (HSC) given systemically can home to the damaged subretinal space and express markers of RPE lineage. Green fluorescent protein (GFP) cells of bone marrow origin were used in a sodium iodate (NAIO(3)) model of RPE damage in the mouse. The optimal time for adoptive transfer of bone marrow-derived stem cells relative to the time of injury and the optimal cell type [whole bone marrow, mobilized peripheral blood, HSC, facilitating cells (FC)] were determined by counting the number of GFP(+) cells in whole eye flat mounts. Immunocytochemistry was performed to identify the bone marrow origin of the cells in the RPE using antibodies for CD45, Sca-1, and c-kit, as well as the expression of the RPE-specific marker, RPE-65. The time at which bone marrow-derived cells were adoptively transferred relative to the time of NaIO3 injection did not significantly influence the number of cells that homed to the subretinal space. At both one and two weeks after intravenous (i.v.) injection, GFP(+) cells of bone marrow origin were observed in the damaged subretinal space, at sites of RPE loss, but not in the normal subretinal space. The combined transplantation of HSC + FC cells appeared to favor the survival of the homed stem cells at two weeks, and R-PE-65 was expressed by adoptively transferred HSC by four weeks. We have shown that systemically injected HSC homed to the subretinal space in the presence of RPE damage and that FC promoted survival of these cells. Furthermore, the RPE-specific marker RPE-65 was expressed on adoptively transferred HSC in the denuded areas. (c) 2006 Elsevier Ltd. All rights reserved.
C1 Univ Bern, Inselspital, Dept Ophthalmol, CH-3010 Bern, Switzerland.
   Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40202 USA.
   Univ Louisville, Inst Cellular Therapeut, Louisville, KY 40202 USA.
   Tokyo Med Univ Hosp, Tokyo, Japan.
C3 University of Bern; University Hospital of Bern; University of
   Louisville; University of Louisville; Tokyo Medical University
RP Enzmann, V (通讯作者)，Univ Bern, Inselspital, Dept Ophthalmol, CH-3010 Bern, Switzerland.
EM volker.enzmann@insel.ch
OI Enzmann, Volker/0000-0003-4384-4855
FU NATIONAL EYE INSTITUTE [R41EY015336] Funding Source: NIH RePORTER; NEI
   NIH HHS [1R41 EY 015336-01A2] Funding Source: Medline
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NR 34
TC 35
Z9 37
U1 0
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2006
VL 83
IS 5
BP 1295
EP 1302
DI 10.1016/j.exer.2006.07.013
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 093WZ
UT WOS:000241202300034
PM 16949576
DA 2022-11-30
ER

PT J
AU Cheong, AMY
   Lovie-Kitchin, JE
   Bowers, AR
   Brown, B
AF Cheong, AMY
   Lovie-Kitchin, JE
   Bowers, AR
   Brown, B
TI Short-term in-office practice improves reading performance with stand
   magnifiers for people with AMD
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE AMD; reading; stand magnifiers; reading rate; training
ID LOW-VISION AIDS; AGE-RELATED MACULOPATHY; HAND-HELD MAGNIFIERS; VISUAL
   REHABILITATION; MACULAR DEGENERATION; CONTRAST SENSITIVITY;
   EYE-MOVEMENTS; OPTICAL AIDS; SPEED; PSYCHOPHYSICS
AB Purpose. People with low vision often use optical low vision aids to assist reading. There have been numerous training programs recommended to train people using magnifiers for reading. However, most of the programs are time consuming and labor intensive. In this study, we investigated the effects of home-based large print reading practice on reading performance when stand magnifiers (STM's) are first prescribed. Methods. Thirty-two subjects with age-related macular degeneration (AMD) and with minimal experience in using magnifiers for reading were recruited. They were divided into three groups: control, practice 1 (PI), and practice 2 (P2). Before the prescription of STM's, all the subjects were given the same amount of in-office practice with the STM (weeks 0 to 2). In addition, in these 2 weeks, P1 and P2 subjects were given large print books to read daily at home. P2 subjects were required to read the large print books through a reduced field of view. The control group subjects received no additional reading practice. Reading rates with and without STM's on passages of text were assessed for all the subjects regularly for 20 weeks. Results. There were no significant differences between the control, P1, and P2 groups in the increase in reading rate with STM (p = 0.29). At week 0, reading rate for small print with STM was significantly slower than reading rate on the equivalent-sized large print (p = 0.004); however, as time went on, reading rate with STM's increased significantly (p = 0.02). After 2 weeks of in-office magnifier practice and repeated measures of reading rate with STM, reading rate with STM had improved such that it was not significantly different from reading rate on large print (p = 0.11). Conclusion. Supervised, short-term, in-office practice with the magnifier was effective in improving magnifier reading performance to achieve maximum reading rate. Additional large print reading practice did not result in any greater improvement in reading rate than in-office magnifier practice alone.
C1 Queensland Univ Technol, Sch Optometry, Ctr Hlth Res, Brisbane, Qld, Australia.
   Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA.
C3 Queensland University of Technology (QUT); Harvard University; Harvard
   Medical School; Schepens Eye Research Institute
RP Cheong, AMY (通讯作者)，Univ Minnesota, Dept Psychol, N218 Elliott Hall,75 E River Rd, Minneapolis, MN 55455 USA.
EM cheon015@umn.edu
RI Cheong, Allen/F-2368-2011; Cheong, Allen Ming Yan/L-9008-2013
OI Bowers, Alex/0000-0002-6038-0178; Cheong, Allen Ming
   Yan/0000-0002-6746-3902
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NR 82
TC 27
Z9 28
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-5488
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD FEB
PY 2005
VL 82
IS 2
BP 114
EP 127
DI 10.1097/01.OPX.0000153244.93582.FF
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 900PW
UT WOS:000227227800005
PM 15711458
DA 2022-11-30
ER

PT J
AU Hillenkamp, J
   Hussain, AA
   Jackson, TL
   Constable, PA
   Cunningham, JR
   Marshall, A
AF Hillenkamp, J
   Hussain, AA
   Jackson, TL
   Constable, PA
   Cunningham, JR
   Marshall, A
TI Compartmental analysis of taurine transport to the outer retina in the
   bovine eye
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID PIGMENT-EPITHELIUM; LIQUID-CHROMATOGRAPHY; PARENTERAL-NUTRITION; NEURAL
   RETINA; AMINO-ACIDS; FROG; PLASMA; POTASSIUM; CAT; DERIVATIZATION
AB PURPOSE. To assess the relative resistance presented individually by Bruch's membrane-choroid (BC) and the retinal pigment epithelium (RPE) to movement of taurine between the choroidal circulation and the outer retina. To quantify the effect of light-evoked changes in subretinal potassium concentration on the transepithelial transport of taurine across bovine RPE.
   METHODS. Transport studies were performed in Ussing chambers with intact and RPE-denuded specimens of BC. RPE viability was monitored by recording transepithelial potential (TEP) and transepithelial resistance (TER). Taurine transport with substrate concentrations in the micro- and millimolar range, reflecting physiological taurine concentrations in plasma, retina, and subretinal space was quantified by high-performance liquid chromatography (HPLC) and radiotracer techniques. Taurine transport was also assessed after apical potassium concentration was lowered from 6.0 to 2.2 mM to mimic the effects of light.
   RESULTS. Transport of taurine across RPE-BC at a 10-mM substrate concentration increased from 32.92 before to 111.72 nanomoles/4 mm per hour after removal of the RPE. Similarly, at 50 muM taurine, transport rates increased from 0.158 to 0.439 nanomoles/4 mm per hour after removal of the RPE. At both high (10 mM) and low (50 muM) substrate concentrations, lowering of apical potassium was associated with decreased transport of taurine across the RPE. For taurine concentrations greater than 42 muM, the rate-limiting compartment for transport of taurine to the outer retina was the RPE monolayer. Similar rates were observed across each compartment for concentrations <42 mu M.
   CONCLUSIONS. The magnitude and directionality of taurine transport across the RPE is determined solely by the driving taurine concentration gradient and is modulated by subretinal levels of potassium. Such modulation may provide a mechanism for conserving retinal taurine. Processes that increase the resistance to diffusion across Bruch's membrane such as human ageing and increased thickening and deposition of debris associated with age-related macular degeneration (AMD) are likely to affect transport across the RPE, culminating in a secondary retinal taurine deficiency.
C1 St Thomas Hosp, Rayne Inst, Dept Ophthalmol, London SE1 7EH, England.
   St Thomas Hosp, Rayne Inst, Dept Pharmacol, London SE1 7EH, England.
C3 Guy's & St Thomas' NHS Foundation Trust; University of London; King's
   College London; Guy's & St Thomas' NHS Foundation Trust; University of
   London; King's College London
RP Hillenkamp, J (通讯作者)，St Thomas Hosp, Rayne Inst, Dept Ophthalmol, Lambeth Palace Rd, London SE1 7EH, England.
EM hillenka@hotmail.com
RI constable, paul/AAF-7227-2019
OI constable, paul/0000-0002-3994-1700; Jackson,
   Timothy/0000-0001-7618-1555
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NR 40
TC 14
Z9 17
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2004
VL 45
IS 11
BP 4099
EP 4105
DI 10.1167/iovs.04-0624
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 865BT
UT WOS:000224678200034
PM 15505061
DA 2022-11-30
ER

PT J
AU Patel, N
   Sun, L
   Moshinsky, D
   Chen, H
   Leahy, KM
   Le, P
   Moss, KG
   Wang, XY
   Rice, A
   Tam, D
   Laird, AD
   Yu, XM
   Zhang, QL
   Tang, C
   McMahon, G
   Howlett, A
AF Patel, N
   Sun, L
   Moshinsky, D
   Chen, H
   Leahy, KM
   Le, P
   Moss, KG
   Wang, XY
   Rice, A
   Tam, D
   Laird, AD
   Yu, XM
   Zhang, QL
   Tang, C
   McMahon, G
   Howlett, A
TI A selective and oral small molecule inhibitor of vascular epithelial
   growth factor receptor (VEGFR)-2 and VEGFR-1 inhibits neovascularization
   and vascular permeability
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID INTRAVITREAL SUSTAINED-RELEASE; RETINAL NEOVASCULARIZATION; MODEL;
   ANGIOGENESIS; SUFFICIENT; BREAKDOWN; MELANOMA; SURVIVAL; BARRIER; EYES
AB Vascular endothelial growth factor (VEGF) is a key driver of the neovascularization and vascular permeability that leads to the loss of visual acuity in diabetic retinopathy and neovascular age-related macular degeneration. Our aim was to identify an orally active, selective small molecule kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-2 with activity against both VEGF-induced angiogenesis and vascular permeability. We used a biochemical assay to identify 3-[5-methyl-2(2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-1H-pyrrol-3-yl]-proprionic acid (SU10944), a pyrrole indolinone, which is a potent ATP-competitive inhibitor of VEGFR-2 (K-i of 21 +/- 5 nM). In cellular assays, SU10944 inhibited VEGF-induced receptor autophosphorylation (IC50 of 227 +/- 80 nM) as well as downstream signaling (IC50 of 102 +/- 27 nM). In biochemical assays, SU10944 exhibits potent inhibitory activity against VEGFR-1; weak activity against other related subgroup members, including stem cell factor receptor (SCFR), platelet-derived growth factor receptor beta (PDGFRbeta), and fibroblast growth factor receptor-1 (FGFR-1); and no detectable activity against other protein tyrosine kinases such as epidermal growth factor receptor (EGFR), Src, and hepatocyte growth factor receptor. In cellular assays, the selectivity for SU10944 to inhibit VEGFR is maintained compared with other tyrosine kinases (IC50 for SCFR of 1.6 +/- 0.3 muM, for PDGFRbeta <LF>of 30.6 +/- 13.3 muM, for FGFR-1 of >50 muM, and for EGFR of >50 muM). Upon oral administration, SU10944 gave a clear dose response in the corneal micropocket model with an ED50 value for inhibition of neovascularization of similar to30 mg/kg and a maximum inhibition of 95% at 300 mg/kg. Similarly, upon oral administration in the Miles assay, SU10944 potently inhibited VEGF-induced vascular permeability. Our data indicate that small molecule inhibitors of VEGFR signaling have the potential to ameliorate VEGF-induced neovascularization as well as vascular permeability.
C1 Sugen Inc, San Francisco, CA 94080 USA.
   Pharmacia Corp, Chesterfield, MI USA.
C3 Pfizer; Pfizer
RP Patel, N (通讯作者)，Sugen Inc, 230 E Grand Ave, San Francisco, CA 94080 USA.
EM neela.patel@sugen.com
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NR 35
TC 33
Z9 39
U1 0
U2 0
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD SEP
PY 2003
VL 306
IS 3
BP 838
EP 845
DI 10.1124/jpet.103.052167
PG 8
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 712UU
UT WOS:000184817400003
PM 12766257
DA 2022-11-30
ER

PT J
AU Kimura, N
   Takahashi, H
   Sakamoto, S
   Yanagi, Y
   Maeshima, N
   Minamimoto, A
   Iwamoto, N
   Shimada, T
   Nagai, R
   Aizawa, K
AF Kimura, Natsuka
   Takahashi, Hidenori
   Sakamoto, Shinichi
   Yanagi, Yasuo
   Maeshima, Nozomi
   Minamimoto, Ayaka
   Iwamoto, Noriko
   Shimada, Takashi
   Nagai, Ryozo
   Aizawa, Kenichi
TI Microvolume Analysis of Aflibercept in Aqueous Humor Using Mass
   Spectrometry
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE aflibercept; vascular endothelial growth factor; intravitreal injection;
   LC-MS; MS; vitreous humor
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL VASCULAR CHANGES; INTRAOCULAR
   PHARMACOKINETICS; MACULAR DEGENERATION; INTRAVITREAL AFLIBERCEPT;
   NANO-SURFACE; VEGF; BEVACIZUMAB; INJECTION; CYTOKINES
AB Purpose: To develop a microvolume analytical method for measurement of the afliber-cept concentration in human intraocular fluid and plasma. Methods: We analyzed trace amounts of aflibercept in human aqueous humor using Fab-selective proteolysis and nano-surface and molecular-orientation limited (nSMOL) proteolysis, coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients with age-related macular degeneration or diabetic macular edema were recruited. Just after an injection of 50 mu L of aflibercept, regurgitate from needle holes was collected with a micropipette pressed to the side of the injection hole within 10 seconds. The median amount of regurgitate was 4 mu L (range, 1-18 mu L). Results: In human plasma, the aflibercept concentration ranged between 0.195 and 50 mu g/mL when using the quantitative signature peptide IIWDSR (aa. 56-61) present on the vascular endothelial growth factor receptor 1 domain of aflibercept. The method was validated by evaluating its linearity, carryover, selectivity, accuracy and precision, dilution effect, and sample/processing stability. As only a minimal amount of regurgi-tate through needle holes can be sampled, we performed and verified the aflibercept assay using patient samples after 1:10 dilution with control human plasma, a recog-nized diluent. The median concentration of aflibercept in the regurgitate was 240 mu g/mL (range, 13-4300 mu g/mL). Conclusions: Our findings indicate that the aflibercept assay using human intraocular fluid can be reliably performed using nSMOL coupled with LC-MS/MS. Translational Relevance: This technique for quantifying aflibercept in the regurgitate suggests that the amount of drug lost post-injection can be ignored, even in patients with a relatively large leak after vitreous injection. This new methodology suggests possible therapeutic responses and may be employed as a general analytical method for trapping many biologics, such as vascular endothelial growth factor, in various types of clinical samples, unaffected by proteinaceous or small organic pharmaceuticals. Assaying Aflibercept in Human Intraocular Fluid Using nSMOL
C1 [Kimura, Natsuka; Aizawa, Kenichi] Jichi Med Univ, Dept Pharmacol, Div Clin Pharmacol, Shimotsuke, Tochigi, Japan.
   [Takahashi, Hidenori; Sakamoto, Shinichi] Jichi Med Univ, Dept Ophthalmol, Shimotsuke, Tochigi, Japan.
   [Yanagi, Yasuo] Yokohama City Univ, Dept Ophthalmol & Microtechnol, Yokohama, Kanagawa, Japan.
   [Yanagi, Yasuo] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Maeshima, Nozomi; Minamimoto, Ayaka] Shimadzu Co Ltd, Global Applicat Dev Ctr, Hadano, Kanagawa, Japan.
   [Iwamoto, Noriko; Shimada, Takashi] Shimadzu Sci Instruments Inc, Shimadzu Biosci Res Partnership, 21720 23rd Dr SE,Suite 250, Bothell, WA 98011 USA.
   [Nagai, Ryozo] Jichi Med Univ, Shimotsuke, Tochigi, Japan.
   [Aizawa, Kenichi] Jichi Med Univ Hosp, Clin Pharmacol Ctr, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan.
C3 Jichi Medical University; Jichi Medical University; Yokohama City
   University; National University of Singapore; Singapore National Eye
   Center; Shimadzu Corporation; Jichi Medical University; Jichi Medical
   University
RP Shimada, T (通讯作者)，Shimadzu Sci Instruments Inc, Shimadzu Biosci Res Partnership, 21720 23rd Dr SE,Suite 250, Bothell, WA 98011 USA.; Aizawa, K (通讯作者)，Jichi Med Univ Hosp, Clin Pharmacol Ctr, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan.
EM t-shima@shimadzu.co.jp; aizawa@jichi.ac.jp
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NR 36
TC 0
Z9 0
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD JUN
PY 2022
VL 11
IS 6
BP 1
EP 12
DI 10.1167/tvst.11.6.7
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 2T5MS
UT WOS:000822519200001
PM 35671043
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Davey, PG
   Henderson, T
   Lem, DW
   Weis, R
   Amonoo-Monney, S
   Evans, DW
AF Davey, Pinakin Gunvant
   Henderson, Thomas
   Lem, Drake W.
   Weis, Rebecca
   Amonoo-Monney, Stephanie
   Evans, David W.
TI Visual Function and Macular Carotenoid Changes in Eyes with Retinal
   Drusen-An Open Label Randomized Controlled Trial to Compare a Micronized
   Lipid-Based Carotenoid Liquid Supplementation and AREDS-2 Formula
SO NUTRIENTS
LA English
DT Article
DE age-related macular degeneration; macular degeneration; macular pigment;
   MPOD; contrast sensitivity; medical food; carotenoids; lutein;
   zeaxanthin; meso-zeaxanthin; Lumega-Z; AREDS-2; PreserVision
ID PIGMENT OPTICAL-DENSITY; AGE-RELATED MACULOPATHY; ZEAXANTHIN
   SUPPLEMENTATION; LUTEIN SUPPLEMENTATION; CONTRAST SENSITIVITY;
   DARK-ADAPTATION; MESO-ZEAXANTHIN; DOUBLE-BLIND; DEGENERATION; SERUM
AB Purpose: To compare the changes in visual and ocular parameters in individuals with retinal drusen who were treated with two commercially available nutritional supplements. Methods: An open-label, single-center, randomized, parallel-treatment with an observational control group design was utilized. The treatment groups included individuals with fine retinal drusen sub-clinical age-related macular degeneration (AMD), while the control group consisted of ocular normal individuals. The treatment groups were randomly assigned to the micronized lipid-based carotenoid supplement, Lumega-Z (LM), or the PreserVision Age-Related Eye Disease Study 2 (AREDS-2) soft gel (PV). Visual performance was evaluated using the techniques of visual acuity, dark adaptation recovery and contrast sensitivity, at baseline, three months, and six months. Additionally, the macular pigment optical density (MPOD) was measured. The control group was not assigned any carotenoid supplement. The right eye and left eye results were analyzed separately. Results: Seventy-nine participants were recruited for this study, of which 68 qualified and 56 participants had useable reliable data. Of the individuals who completed this study, 25 participants belonged to the LM group, 16 belonged to the PV group, and 15 to the control group. The LM group demonstrated statistically significant improvements in contrast sensitivity function (CSF) in both eyes at six months (p < 0.001). The LM group displayed a positive linear trend with treatment time in CSF (p < 0.001), with benefits visible after just three months of supplementation. Although there was a trend showing improvement in CSF in the PV group, the change was not significant after a Bonferroni-corrected p-value of p < 0.00625. Visual acuity, dark adaptation recovery and MPOD did not significantly improve in either treatment groups. Conclusion: The LM group demonstrated greater and faster benefits in visual performance as measured by CSF when compared to the PV group. This trial has been registered at clinicaltrials.gov (NCT03946085).
C1 [Davey, Pinakin Gunvant; Lem, Drake W.; Amonoo-Monney, Stephanie] Western Univ Hlth Sci, Coll Optometry, Pomona, CA 91766 USA.
   [Henderson, Thomas; Weis, Rebecca] Eye Clin Austin, Austin, TX 78731 USA.
   [Evans, David W.] VectorVis Guard Hlth Sci, San Diego, CA 92128 USA.
C3 Western University of Health Sciences
RP Davey, PG (通讯作者)，Western Univ Hlth Sci, Coll Optometry, Pomona, CA 91766 USA.
EM contact@pinakin-gunvant.com; thendersonmd@outlook.com;
   drake.lem@westernu.edu; rweis@eyeclinicofaustin.com;
   samonoomonney@westernu.edu; devans@vectorvision.com
RI Davey, Pinakin/AAK-9804-2021; Davey, Pinakin/AAI-9869-2021
OI Davey, Pinakin/0000-0002-6683-7052; Lem, Drake/0000-0003-1060-9162
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NR 75
TC 8
Z9 8
U1 1
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-6643
J9 NUTRIENTS
JI Nutrients
PD NOV
PY 2020
VL 12
IS 11
AR 3271
DI 10.3390/nu12113271
PG 16
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA OZ1BM
UT WOS:000594670200001
PM 33114566
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Brosig, A
   Kuhrt, H
   Wiedemann, P
   Kohen, L
   Bringmann, A
   Hollborn, M
AF Brosig, Anton
   Kuhrt, Heidrun
   Wiedemann, Peter
   Kohen, Leon
   Bringmann, Andreas
   Hollborn, Margrit
TI Gene expression regulation in retinal pigment epithelial cells induced
   by viral RNA and viral/bacterial DNA
SO MOLECULAR VISION
LA English
DT Article
ID CHLAMYDIA-PNEUMONIAE INFECTION; HUMAN RPE CELLS; MACULAR DEGENERATION;
   CHOROIDAL NEOVASCULARIZATION; GROWTH-FACTOR; KAPPA-B; ACTIVATION;
   DRUSEN; PATHOGENESIS; ASSOCIATION
AB Purpose:The pathogenesis of age-related macular degeneration (AMD) is associated with systemic and local inflammation. Various studies suggested that viral or bacterial infection may aggravate retinal inflammation in the aged retina. We compared the effects of synthetic viral RNA (poly(I:C)) and viral/bacterial DNA (CpG-ODN) on the expression of genes known to be involved in the development of AMD in retinal pigment epithelial (RPE) cells.
   Methods:Cultured human RPE cells were stimulated with poly(I:C; 500 mu g/ml) or CpG-ODN (500 nM). Alterations in gene expression and protein secretion were determined with real-time RT-PCR and ELISA, respectively. Phosphorylation of signal transduction molecules was revealed by western blotting.
   Results:Poly(I:C) induced gene expression of the pattern recognition receptor TLR3, transcription factors (HIF-1 alpha, p65/NF-kappa B), the angiogenic factor bFGF, inflammatory factors (IL-1 beta, IL-6, TNF alpha, MCP-1, MIP-2), and complement factors (C5, C9, CFB). Poly(I:C) also induced phosphorylation of ERK1/2 and p38 MAPK proteins, and the secretion of bFGF and TNFa from the cells. CpG-ODN induced moderate gene expression of transcription factors (p65/NF-kappa B, NFAT5) and complement factors (C5, C9), while it had no effect on the expression of various TLR, angiogenic factor, and inflammatory factor genes. The activities of various signal transduction pathways and transcription factors were differentially involved in mediating the poly(I:C)-induced transcriptional activation of distinct genes.
   Conclusions:The widespread effects of viral RNA, and the restricted effects of viral/bacterial DNA, on the gene expression pattern of RPE cells may suggest that viral RNA rather than viral/bacterial DNA induces physiologic alterations of RPE cells, which may aggravate inflammation in the aged retina. The data also suggest that selective inhibition of distinct signal transduction pathways or individual transcription factors may not be effective to inhibit viral retinal inflammation.
C1 [Brosig, Anton; Wiedemann, Peter; Kohen, Leon; Bringmann, Andreas; Hollborn, Margrit] Univ Leipzig, Dept Ophthalmol, D-04103 Leipzig, Germany.
   [Brosig, Anton; Wiedemann, Peter; Kohen, Leon; Bringmann, Andreas; Hollborn, Margrit] Univ Leipzig, Hosp Eye, D-04103 Leipzig, Germany.
   [Kuhrt, Heidrun] Univ Leipzig, Paul Flechsig Inst Brain Res, D-04103 Leipzig, Germany.
   [Kohen, Leon] Helios Klinikum Aue, Aue, Germany.
C3 Leipzig University; Leipzig University; Leipzig University; Helios
   Kliniken
RP Hollborn, M (通讯作者)，Univ Leipzig, Fac Med, Dept Ophthalmol, Liebigstr 10-14, D-04103 Leipzig, Germany.
EM hollbm@medizin.uni-leipzig.de
RI Kuhrt, Heidrun/A-5274-2017
FU Deutsche Forschungsgemeinschaft [KO 1547/7-1]; Geschwister Freter
   Stiftung (Hannover, Germany)
FX The authors thank Ute Weinbrecht for excellent technical assistance.
   This study was supported by grants from the Deutsche
   Forschungsgemeinschaft (KO 1547/7-1 to L.K.) and the Geschwister Freter
   Stiftung (Hannover, Germany).
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NR 40
TC 10
Z9 10
U1 0
U2 5
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD AUG 31
PY 2015
VL 21
BP 1000
EP 1016
PG 17
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA CQ1HZ
UT WOS:000360349200001
PM 26330750
DA 2022-11-30
ER

PT J
AU Lee, AY
   Lee, CS
   Butt, T
   Xing, W
   Johnston, RL
   Chakravarthy, U
   Egan, C
   Akerele, T
   McKibbin, M
   Downey, L
   Natha, S
   Bailey, C
   Khan, R
   Antcliff, R
   Varma, A
   Kumar, V
   Tsaloumas, M
   Mandal, K
   Liew, G
   Keane, PA
   Sim, D
   Bunce, C
   Tufail, A
AF Lee, Aaron Y.
   Lee, Cecilia S.
   Butt, Thomas
   Xing, Wen
   Johnston, Robert L.
   Chakravarthy, Usha
   Egan, Catherine
   Akerele, Toks
   McKibbin, Martin
   Downey, Louise
   Natha, Salim
   Bailey, Clare
   Khan, Rehna
   Antcliff, Richard
   Varma, Atul
   Kumar, Vineeth
   Tsaloumas, Marie
   Mandal, Kaveri
   Liew, Gerald
   Keane, Pearse A.
   Sim, Dawn
   Bunce, Catey
   Tufail, Adnan
CA UK AMD EMR Users Grp
TI UK AMD EMR USERS GROUP REPORT V: benefits of initiating ranibizumab
   therapy for neovascular AMD in eyes with vision better than 6/12
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; RANDOMIZED-TRIAL; PREVALENCE; BURDEN; DELAY; HOME
AB Background/aims To study the effectiveness and clinical relevance of eyes treated with good (better than 6/12 or >70 Early Treatment Diabetic Retinopathy Study letters) visual acuity (VA) when initiating treatment with ranibizumab for neovascular age-related macular degeneration (nAMD) in the UK National Health Service. Currently eyes with VA better than (>) 6/12 are not routinely funded for therapy.
   Methods Multicentre national nAMD database study on patients treated 3-5 years prior to the analysis. Anonymised structured data were collected from 14 centres. The primary outcome was the mean VA at year 1, 2 and 3. Secondary measures included the number of clinic visits and injections.
   Results The study included 12 951 treatment-naive eyes of 11 135 patients receiving 92 976 ranibizumab treatment episodes. A total of 754 patients had baseline VA better than 6/12 and at least 1-year of follow up. Mean VA of first treated eyes with baseline VA>6/12 at year 1, 2, 3 were 6/10, 6/12, 6/15, respectively and those with baseline VA 6/12 to >6/24 were 6/15, 6/17, 6/20, respectively (p values < 0.001 for comparing differences between 6/12 and 6/12-6/24 groups). For the second eyes with baseline VA>6/12, mean VA at year 1, 2, 3 were 6/9, 6/9, 6/10 and those with baseline VA 6/12 to >6/24 were 6/15, 6/15, 6/27, respectively (p values < 0.001-0.005). There was no significant difference in the average number of clinic visits or injections between those with VA better and worse than 6/12.
   Conclusions All eyes with baseline VA>6/12 maintained better mean VA than the eyes with baseline VA 6/12 to >6/24 at all time points for at least 2 years. The significantly better visual outcome in patients who were treated with good baseline VA has implications on future policy regarding the treatment criteria for nAMD patients' funding.
C1 [Lee, Aaron Y.; Egan, Catherine; Keane, Pearse A.; Sim, Dawn; Bunce, Catey; Tufail, Adnan] Moorfields Eye Hosp NHS Fdn Trust, London, England.
   [Lee, Cecilia S.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA.
   [Butt, Thomas] UCL, Inst Ophthalmol, London, England.
   [Xing, Wen] Moorfields Eye Hosp NHSFT, R&D, London, England.
   [Johnston, Robert L.] Cheltenham Gen Hosp, Gloucestershire Eye Dept, Cheltenham, Glos, England.
   [Chakravarthy, Usha] Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland.
   [Akerele, Toks] Hinchingbrooke Hlth Care NHS Trust, Hinchingbrooke, Cambs, England.
   [McKibbin, Martin] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England.
   [Downey, Louise] Hull & East Yorkshire Hosp NHS Trust, Kingston Upon Hull, N Humberside, England.
   [Natha, Salim] Wigan & Leigh NHS Fdn Trust, Wrightington, Wigan, England.
   [Bailey, Clare] Bristol Eye Hosp, Bristol BS1 2LX, Avon, England.
   [Khan, Rehna] Calderdale & Huddersfield NHS Fdn Trust, Huddersfield, W Yorkshire, England.
   [Antcliff, Richard] Royal United Hosp Bath NHS Trust, Bath, Avon, England.
   [Varma, Atul] Mid Yorkshire Hosp NHS Trust, Wakefield, Yorks, England.
   [Kumar, Vineeth] Wirral Univ, Teaching Hosp, NHS Fdn Trust, Wirral, Merseyside, England.
   [Tsaloumas, Marie] Univ Hosp Birmingham NHS Fdn Trust, Dept Ophthalmol, Birmingham, W Midlands, England.
   [Mandal, Kaveri] Warrington & Halton Hosp NHS Fdn Trust, Dept Ophthalmol, Warrington, Cheshire, England.
   [Liew, Gerald] Univ Sydney, Ctr Vis Res, Sydney, NSW 2006, Australia.
   [Sim, Dawn] UCL Inst Ophthalmol, Dept Cell Biol, London, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of Washington; University of Washington
   Seattle; University of London; University College London; University of
   London; University College London; Moorfields Eye Hospital NHS
   Foundation Trust; Gloucestershire Hospitals NHS Foundation Trust;
   Cheltenham General Hospital; University of Leeds; Bristol Eye Hospital;
   Oxford University Hospitals NHS Foundation Trust; University of
   Liverpool; University of Birmingham; University of Sydney; University of
   London; University College London
RP Tufail, A (通讯作者)，Moorfields Eye Hosp NHS Trust, Dept Med Retina, 162 City Rd, London EC1V 2PD, England.
EM Adnan.Tufail@moorfields.nhs.uk
RI Lee, Aaron/AAT-2839-2020; Keane, Pearse/AAE-5709-2019; Zarranz-Ventura,
   Javier/AAB-5390-2021; Butt, Thomas/AAH-7882-2019; Liew,
   Gerald/AAB-6870-2022; Lee, Cecilia/K-2569-2014; Sallam,
   Ahmed/A-4791-2014
OI Keane, Pearse/0000-0002-9239-745X; Zarranz-Ventura,
   Javier/0000-0003-2338-8143; Butt, Thomas/0000-0002-0387-4550; Lee,
   Cecilia/0000-0003-1994-7213; McKibbin, Martin/0000-0003-4388-243X;
   Tufail, Adnan/0000-0001-6131-7640; Chakravarthy,
   Usha/0000-0002-2606-3734; Sallam, Ahmed/0000-0001-7207-6782; Egan,
   Catherine/0000-0001-5593-1169; Lee, Aaron/0000-0002-7452-1648; Bunce,
   Catey/0000-0002-0935-3713
FU Novartis Pharmaceuticals; NOTAL Vision; Department of Health's NIHR
   Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital;
   UCL Institute of Ophthalmology; Academy of Medical Sciences (AMS)
   [AMS-SGCL6-Keane] Funding Source: researchfish; National Institute for
   Health Research [CL-2010-18-004] Funding Source: researchfish; NATIONAL
   EYE INSTITUTE [K23EY024921] Funding Source: NIH RePORTER
FX This work was supported in part by an unrestricted research award by
   Novartis Pharmaceuticals and NOTAL Vision. No member or affiliate of
   Novartis or Notal Vision had any input into data analysis, the
   interpretation of the data or writing the manuscript. This research has
   received a proportion of its funding from the Department of Health's
   NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye
   Hospital and UCL Institute of Ophthalmology. The views expressed in the
   publication are those of the authors and not necessarily those of the
   Department of Health.
CR [Anonymous], 2014, RAN PEG TREATM AG RE
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NR 23
TC 46
Z9 46
U1 0
U2 7
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD AUG
PY 2015
VL 99
IS 8
BP 1045
EP 1050
DI 10.1136/bjophthalmol-2014-306229
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CN3BC
UT WOS:000358297200007
PM 25680619
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Downie, LE
   Keller, PR
AF Downie, Laura Elizabeth
   Keller, Peter Richard
TI The Self-Reported Clinical Practice Behaviors of Australian Optometrists
   as Related to Smoking, Diet and Nutritional Supplementation
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; CIGARETTE-SMOKING; FATTY-ACIDS;
   GENERAL-PRACTITIONERS; AGE; RISK; CESSATION; OMEGA-3; CARE; CONSUMPTION
AB Objective
   The primary aim of this study was to examine the self-reported, routine clinical practice behaviors of Australian optometrists with respect to advice regarding smoking, diet and nutritional supplementation. The study also sought to assess the potential influence of practitioner age, gender, practice location (major city versus regional), therapeutic-endorsement status and personal nutritional supplementation habits upon management practices in these areas.
   Methods
   A survey was electronically distributed to Australian optometrists (n = 4,242). Respondents anonymously provided information about their personal demographics and lifestyle behaviors (i.e., age, gender, practice location, therapeutic-endorsement status, smoking status, nutritional supplement intake) and routine patient management practices with respect to advice across three domains: smoking, diet and nutritional supplementation. Multivariate logistic regression analyses were performed to assess for potential effects of the listed factors on practitioner behavior.
   Results
   A total of 283 completed surveys were received (completed survey response rate: 6.7%). Fewer than half of respondents indicated routinely asking their patients about smoking status. Younger practitioners were significantly (p < 0.05) less likely to enquire about patients' smoking behaviors, but this did not extend to counseling for smoking cessation. Almost two-thirds of respondents indicated routinely counseling patients about diet. About half of practitioners specified routinely asking their patients about nutritional supplement intake; this form of questioning was significantly more likely if the respondent was female (p < 0.05). Practitioners who recommended nutritional supplements most commonly did so for age-related macular degeneration (91.2%) and dry eye disease (63.9%). The primary source of evidence used to guide practitioners' nutrition-related patient management was reported to be peer-reviewed publications.
   Conclusions
   These findings demonstrate that there are no clear predictors of practitioner behavior across the three domains. Overall, this study suggests that there is scope for Australian optometrists to improve their routine engagement by questioning patients, as well as providing evidence-based clinical advice, about smoking status, diet and nutritional supplement behaviors, being key modifiable lifestyle risk factors with long-term implications for eye health.
C1 [Downie, Laura Elizabeth; Keller, Peter Richard] Univ Melbourne, Dept Optometry & Vis Sci, Parkville, Vic 3010, Australia.
   [Keller, Peter Richard] Ctr Eye Res Australia, Macular Res Unit, East Melbourne, Vic 3002, Australia.
C3 University of Melbourne; Centre for Eye Research Australia
RP Downie, LE (通讯作者)，Univ Melbourne, Dept Optometry & Vis Sci, Parkville, Vic 3010, Australia.
EM ldownie@unimelb.edu.au
OI Keller, Peter/0000-0003-4431-184X; Downie, Laura/0000-0002-1596-2259
CR [Anonymous], TREATING TOBACCO USE
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NR 49
TC 21
Z9 21
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 17
PY 2015
VL 10
IS 4
AR e0124533
DI 10.1371/journal.pone.0124533
PG 16
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CG1EX
UT WOS:000353017000135
PM 25886641
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Huo, XC
   Li, YX
   Jiang, YH
   Sun, XY
   Gu, LX
   Guo, WS
   Sun, DP
AF Huo, Xiaochuan
   Li, Youxiang
   Jiang, Yuhua
   Sun, Xiaoyun
   Gu, Lixue
   Guo, Wenshi
   Sun, Dapeng
TI Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and
   PLGF
SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
LA English
DT Article
DE Age-related macular degeneration (AMD); Choroidal neovascularization
   (CNV); Placental growth factor (PLGF); Vascular endothelial growth
   factor A (VEGF-A); Laser burn (LB); Macrophages
ID ENDOTHELIAL GROWTH-FACTOR; HUMAN CHOROIDAL NEOVASCULARIZATION; MACULAR
   DEGENERATION; PANCREATIC-CANCER; TUMOR-GROWTH; LASER BURN; IN-VIVO;
   CELL; RANIBIZUMAB; THERAPY
AB Background/Aims: Age-related macular degeneration (AMD) appears to be a disease with increasing incidence in Western countries and may develop into acquired blindness. Choroidal neovascularization (CNV) is the most frequent cause for AMD, and is commonly induced by regional inflammation. Past studies have highlighted vascular endothelial growth factor A (VEGF-A) as a major trigger for CNV. However, studies on the associated angiogenic factors other than VEGF-A are lacking. Methods: Here, we used a well-established laser burn (LB)-induced experimental CNV mouse model to study the molecular mechanisms underlying the development of CNV after ocular injury. We analyzed vessel density by lectin labeling. We isolated macrophages, endothelial cells and other cell types by flow cytometry, and analyzed levels of different angiogenic factors in these populations. We used antisera against VEGF-A (aVEGF) and/or antisera against placental growth factor (PLGF; aPLGF) to antagonize CNV. We used an antibody-driven toxin to selectively eliminate macrophages to evaluate the role of macrophages in CNV. We also examined expression of PLGF in macrophage subtypes. Results: The choroidal vessel density increased significantly 7 days after LB. LB increased significantly the levels of VEGF-A and PLGF in mouse eyes. Treatment with aVEGF significantly blunted increases in vessel density by LB. Treatment with aPLGF alone did not significantly reduce increases in vessel density. However, aPLGF significantly increased the inhibitory effects of aVEGF on vessel density increases. While VEGF-A was produced by endothelial cells, macrophages and other types at similar levels, PLGF seemed to be predominantly produced by macrophages. Selective macrophage depletion significantly reduced CNV. M2, but M1 macrophages produced high levels of PLGF. Conclusions: Together, our data suggest a previously unappreciated role of PLGF in coordination with VEGF-A to regulate CNV during ocular injury. Our study highlights macrophages and their production of PLGF as novel targets for CNV therapy. Copyright (C) 2015 S. Karger AG, Basel
C1 [Huo, Xiaochuan; Li, Youxiang; Jiang, Yuhua] Capital Med Univ, Beijing Tiantan Hosp, Beijing Neurosurg Inst, Dept Intervent Neuroradiol, Beijing, Peoples R China.
   [Sun, Xiaoyun; Gu, Lixue; Guo, Wenshi] Liaoning Med Univ, Affiliated Hosp 1, Dept Neurosurg, Jinzhou, Peoples R China.
   [Sun, Dapeng] China Med Univ, Year Program 1B 96K 7, Shenyang 110001, Peoples R China.
C3 Beijing Neurosurgical Institute; Capital Medical University; Jinzhou
   Medical University; China Medical University
RP Li, YX (通讯作者)，Beijing Neurosurg Inst, 6 Tiantan Xili, Beijing 100050, Peoples R China.
EM liyouxiang15@163.com
OI LI, Youxiang/0000-0002-3995-4106
FU Natural Science Foundation of China [81171111]; Natural Science
   Foundation of Liaoning Province of China [2013022016]
FX This study was supported by Natural Science Foundation of China (No.
   81171111) and Natural Science Foundation of Liaoning Province of China
   (No. 2013022016).
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NR 36
TC 30
Z9 32
U1 0
U2 5
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1015-8987
EI 1421-9778
J9 CELL PHYSIOL BIOCHEM
JI Cell. Physiol. Biochem.
PY 2015
VL 35
IS 5
BP 1787
EP 1796
DI 10.1159/000373990
PG 10
WC Cell Biology; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Physiology
GA CH0MG
UT WOS:000353713900011
PM 25832861
OA gold
DA 2022-11-30
ER

PT J
AU Lavric, A
   Pompe, MT
AF Lavric, Alenka
   Pompe, Manca Tekavcic
TI Do Blue-Light Filtering Intraocular Lenses Affect Visual Function?
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE blue light; filter; intraocular lens; contrast sensitivity; color
   vision; macula; age-related macular degeneration; yellow IOL
ID CONTRAST SENSITIVITY; MACULAR DEGENERATION; COLOR-VISION;
   CATARACT-SURGERY; EYE; AUTOFLUORESCENCE; PSEUDOPHAKIA; TRANSMISSION;
   DISTURBANCE; EXPOSURE
AB Purpose. To study different aspects of visual function, macular changes, and subjective differences between the eye with an ultraviolet (UV) and blue-light filtering intraocular lens (IOL) and the fellow eye with a UV-light filtering IOL.
   Methods. Thirty patients (60 eyes) with senile cataract had both cataracts extracted, and an IOL was implanted at least 2 years before clinical evaluation. In one eye, AcrySof SA60AT (a UV-light filtering IOL) was implanted, whereas in the contralateral eye, AcrySof IQ SN60WF (a blue-light filtering IOL) was implanted. Each patient underwent visual acuity testing, color vision testing (Ishihara and Farnsworth-Munsell 100-hue tests), and contrast sensitivity (CS) testing. The macula was evaluated with optical coherence tomography and with clinical examination. Patients were asked if they noted any difference between the implanted IOLs concerning visual impression. Subjective visual quality was evaluated using the National Eye Institute Visual Functioning Questionnaire.
   Results. There was a borderline statistically significant difference in the mean best-corrected visual acuity (p = 0.05). As regards color vision, no significant changes in Ishihara and Farnsworth-Munsell 100-hue error scores were detected between both eyes (p = 0.48 and p = 0.59, respectively). Analysis of CS showed no significant difference between the groups at any spatial frequency. There were also no statistically significant differences in central macular thickness and total macular volume between the two IOL groups (p = 0.72 and p = 0.61, respectively). In both IOL groups, three eyes developed an epiretinal membrane, and six eyes developed early signs of age-related macular degeneration.
   Conclusions. This study showed no significant effects of a blue-light filtering IOL on visual acuity and no influence on color perception and CS. After more than 2 years, there were no significant differences in macular changes between the IOL groups. Clinical evidence of the effect of a blue-light filtering IOL on macular protection is still lacking.
C1 [Lavric, Alenka; Pompe, Manca Tekavcic] Univ Med Ctr Ljubljana, Hosp Eye, SI-1000 Ljubljana, Slovenia.
C3 University Medical Centre Ljubljana
RP Lavric, A (通讯作者)，Univ Med Ctr Ljubljana, Hosp Eye, Grabloviceva 46, SI-1000 Ljubljana, Slovenia.
EM lavricalenka@gmail.com
RI Tekavcic-Pompe, Manca/AAE-8118-2021; Tekavčič Pompe, Manca/AFV-3295-2022
OI Tekavčič Pompe, Manca/0000-0003-3730-0229; Lavric,
   Alenka/0000-0002-9854-6241
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NR 45
TC 11
Z9 12
U1 0
U2 26
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-5488
EI 1538-9235
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD NOV
PY 2014
VL 91
IS 11
BP 1348
EP 1354
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AT7LE
UT WOS:000345117300016
PM 25216318
DA 2022-11-30
ER

PT J
AU Bertelsen, G
   Erke, MG
   von Hanno, T
   Mathiesen, EB
   Peto, T
   Sjolie, AK
   Njolstad, I
AF Bertelsen, Geir
   Erke, Maja G.
   von Hanno, Therese
   Mathiesen, Ellisiv B.
   Peto, Tunde
   Sjolie, Anne K.
   Njolstad, Inger
TI The Tromso Eye Study: study design, methodology and results on visual
   acuity and refractive errors
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; diabetic retinopathy; epidemiology;
   refractive error; retinal vasculature; retinal vessel calibre; TromsO
   Eye Study; TromsO Study; visual acuity
ID RETINAL MICROVASCULAR ABNORMALITIES; AGE-RELATED MACULOPATHY;
   CORONARY-HEART-DISEASE; DIABETIC-RETINOPATHY; ATHEROSCLEROSIS RISK;
   OLDER POPULATION; VESSEL MEASUREMENT; MACULAR EDEMA; IMPAIRMENT;
   PREVALENCE
AB . Purpose: To describe the study design and methodology of the TromsO Eye Study (TES), and to describe visual acuity and refractive error in the study population. Methods: The TromsO Eye Study is a sub-study of the TromsO Study, a population-based multipurpose longitudinal study in the municipality of TromsO, Norway. The TromsO Eye Study was a part of the sixth survey of the TromsO Study, conducted from October 2007 through December 2008. The eye examination included information on self-reported eye diseases, assessment of visual acuity and refractive errors, retinal photography and optical coherence tomography. Retinal images were graded for diabetic retinopathy and age-related macular degeneration, and with computer-assisted measurements of arteriolar and venular diameters. In addition, TES researchers have access to the large comprehensive TromsO Study database including physical examination results, carotid artery ultrasound, electrocardiogram, bone densitometry, cognitive tests, questionnaires, DNA, blood and urine samples and more from the present and the five previous surveys. Results: Visual acuity was assessed in 6459 subjects and refraction in 6566 subjects aged 38-87years. Snellen visual acuity <20/60 was found in 1.2% (95% CI 0.95-1.5) of the participants and there was no gender difference. Visual impairment increased with age, and in the age group 80-87years, the overall visual acuity <20/60 was 7.3% (95% CI 3.3-11.2). Spherical equivalent showed an increasing trend with age and there was no clinically relevant difference between men and women. Retinal photography was performed in 6540 subjects. Conclusion: Prevalence of visual impairment was low but increased with age. There was a trend towards hyperopia with age and no clinically relevant difference in refraction between the sexes. TES aims to provide epidemiological research on several eye and eye-related diseases. Owing to a comprehensive data collection, it has the opportunity to explore issues related to environmental factors, cognition and their interaction with diseases in this community.
C1 [Bertelsen, Geir; Erke, Maja G.] Univ Hosp North Norway, Dept Ophthalmol & Neurosurg, Tromso, Norway.
   [Bertelsen, Geir; Erke, Maja G.; Njolstad, Inger] Univ Tromso, Dept Community Med, Fac Hlth Sci, Res Grp Epidemiol Chron Dis, Tromso, Norway.
   [von Hanno, Therese; Mathiesen, Ellisiv B.; Sjolie, Anne K.] Univ Tromso, Fac Hlth Sci, Dept Clin Med, Brain & Circulat Res Grp, Tromso, Norway.
   [von Hanno, Therese] Nordland Hosp, Dept Ophthalmol, Bodo, Norway.
   [Mathiesen, Ellisiv B.] Univ Hosp North Norway, Dept Neurol & Neurophysiol, Tromso, Norway.
   [Peto, Tunde] NHS Fdn Trust, Moorfields Eye Hosp, NIHR Biomed Res Ctr Ophthalmol, London, England.
   [Peto, Tunde] UCL Inst Ophthalmol, Reading Ctr, London, England.
   [Sjolie, Anne K.] Odense Univ Hosp, Dept Ophthalmol, DK-5000 Odense, Denmark.
C3 UiT The Arctic University of Tromso; University Hospital of North
   Norway; UiT The Arctic University of Tromso; UiT The Arctic University
   of Tromso; UiT The Arctic University of Tromso; University Hospital of
   North Norway; Oxford University Hospitals NHS Foundation Trust;
   University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London;
   University of Southern Denmark; Odense University Hospital
RP Bertelsen, G (通讯作者)，Univ Tromso, Fac Hlth Sci, Dept Community Med, N-9037 Tromso, Norway.
EM geir.bertelsen@uit.no
RI Bertelsen, Geir/ABB-9865-2021; Njolstad, Inger/X-3784-2019; Peto,
   Tunde/G-8812-2018
OI Peto, Tunde/0000-0001-6265-0381
FU Norwegian Extra Foundation for Health and Rehabilitation through EXTRA
   funds; Research Council of Norway, University of Tromso; North Norway
   Regional Health Authority; Simon Fougner Hartmanns Familiefond; NIHR
   Biomedical Research Centre for Ophthalmology, at Moorfields Eye Hospital
   NHS Foundation Trust
FX TES has been financially supported by the Norwegian Extra Foundation for
   Health and Rehabilitation through EXTRA funds, the Research Council of
   Norway, University of Tromso, the North Norway Regional Health Authority
   and Simon Fougner Hartmanns Familiefond. Tunde Peto would like to say
   thank you to NIHR Biomedical Research Centre for Ophthalmology, at
   Moorfields Eye Hospital NHS Foundation Trust for funding her
   participation in this study. We thank the Retinal Vascular Imaging
   Centre, Centre for Eye Research Australia, University of Melbourne, for
   training, grading, discussion and valuable advice. We thank Terje
   Christoffersen, Anette Lade and Haakon Lindekleiv for punching data on
   refraction.
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NR 51
TC 20
Z9 20
U1 0
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD NOV
PY 2013
VL 91
IS 7
BP 635
EP 642
DI 10.1111/j.1755-3768.2012.02511.x
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 270MR
UT WOS:000328323000026
PM 22963377
OA Bronze
DA 2022-11-30
ER

PT J
AU Stewart, EA
   Samaranayake, GJ
   Browning, AC
   Hopkinson, A
   Amoaku, WM
AF Stewart, Elizabeth A.
   Samaranayake, Govindi J.
   Browning, Andrew C.
   Hopkinson, Andrew
   Amoaku, Winfried M.
TI Comparison of choroidal and retinal endothelial cells: Characteristics
   and response to VEGF isoforms and anti-VEGF treatments
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; ocular neovascularisation; endothelial
   cell; ranibizumab; bevacizumab; pegaptanib; retina; choroid
ID GROWTH-FACTOR; IN-VITRO; VASCULAR-PERMEABILITY; CLINICAL-IMPLICATIONS;
   MACULAR DEGENERATION; RANIBIZUMAB; NEOVASCULARIZATION; ANGIOGENESIS;
   EXPRESSION; BEVACIZUMAB
AB Neovascular eye diseases such as wet age-related macular degeneration and proliferative diabetic retinopathy are two of the most common causes of irreversible visual loss. Although mediated by vascular endothelial growth factor (VEGF), the mechanisms of these diseases are not fully understood. Molecular inhibitors of VEGF including pegaptanib, ranibizumab and bevacizumab are used as treatments for these diseases. However, there have been very few direct comparisons between these agents, and as dose and treatment regimes differ their relative efficacies are hard to determine. In vitro comparisons tend to use cells from different sites or species, which show heterogeneity in their responses. The aim of this study was to compare the characteristics of primary cultures of isolated human choroidal endothelial cells (hCEC) and retinal endothelial cells (hREC), and their proliferation responses to stimulation with VEGF 121 and 165, and to compare the anti-proliferative effects of these three drugs. hCEC and hREC were positive for the cell markers VEGFR1, VEGFR2, CD31, CD34 and von Willebrand's factor (vWF), with greater expression of CD34 on the hREC compared to hCEC. Contrary to previous assumptions VEGF isoforms 121 and 165 were found to be equally potent in stimulating endothelial cell proliferation. However, hREC exhibited higher proliferation with either VEGF isoform compared to hCEC. The anti-VEGF treatments ranibizumab and bevacizumab were effective in decreasing proliferation of hCEC induced by the two VEGF isoforms, individually and in combination, with ranibizumab being moderately more effective, particularly in hREC. Pegaptanib was effective in controlling the proliferation of hCEC stimulated by VEGF 165, but was ineffective against the stimulatory effect of VEGF 121. There were found to be significant differences in microvascular endothelial cells from the retina and choroid, both in the expression of cell markers and their behaviour in response to growth factors and currently available anti-VEGF agents, highlighting the importance of targeting treatments to specific intraocular vascular beds and/or diseases. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Stewart, Elizabeth A.; Samaranayake, Govindi J.; Browning, Andrew C.; Hopkinson, Andrew; Amoaku, Winfried M.] Univ Nottingham, Div Ophthalmol & Visual Sci, Queens Med Ctr, Nottingham NG7 2UH, England.
C3 University of Nottingham
RP Amoaku, WM (通讯作者)，Univ Nottingham, Div Ophthalmol & Visual Sci, Queens Med Ctr, B Floor,Eye & ENT Bldg, Nottingham NG7 2UH, England.
EM Elizabeth.stewart@nottingham.ac.uk; andrew_browning@talk21.com;
   Andrew.hopkinson@nottingham.ac.uk; wma@nottingham.ac.uk
RI Hopkinson, Andrew/A-2287-2011; Stewart, Elizabeth/K-5013-2014
OI Stewart, Elizabeth A/0000-0002-6248-4464; Samaranayake,
   Govindi/0000-0002-4186-5401; Amoaku, Winfried/0000-0001-5028-7984
CR Adamis AP, 1996, ARCH OPHTHALMOL-CHIC, V114, P66, DOI 10.1001/archopht.1996.01100130062010
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NR 39
TC 49
Z9 51
U1 0
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2011
VL 93
IS 5
BP 761
EP 766
DI 10.1016/j.exer.2011.09.010
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 855AK
UT WOS:000297535700023
PM 21970900
DA 2022-11-30
ER

PT J
AU Hogg, RE
   Woodside, JV
   Gilchrist, SECM
   Graydon, R
   Fletcher, AE
   Chan, W
   Knox, A
   Cartmill, B
   Chakravarthy, U
AF Hogg, Ruth E.
   Woodside, Jayne V.
   Gilchrist, Sarah E. C. M.
   Graydon, Ryan
   Fletcher, Astrid E.
   Chan, Wing
   Knox, Angela
   Cartmill, Barry
   Chakravarthy, Usha
TI Cardiovascular disease and hypertension are strong risk factors for
   choroidal neovascularization
SO OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; C-REACTIVE PROTEIN; BODY-MASS INDEX; LEUKOCYTE
   ADHESION MOLECULES; MACULAR DEGENERATION; POOLED FINDINGS; CHOLESTEROL;
   PREVALENCE; MARKERS; PLASMA
AB Purpose: To investigate the association of cardiovascular risk factors and inflammatory markers with neovascular age-related macular degeneration (AMD).
   Design: Cross-sectional case-control study.
   Participants: Of the 410 of the >= 65-year-old community sample invited to attend, 205 participated (50% response rate). Of the 215 clinic attendees who were invited to participate, 212 agreed to take part (98% response rate). A diagnosis of neovascular AMD in at least one eye was made in 193 clinic attendees and 2 of the community sample.
   Methods: Clinic and community participants underwent a detailed ophthalmic examination with fundus imaging, were interviewed for assessment of putative risk factors, and provided a blood sample. Analysis included levels of serum lipids, intercellular adhesion molecule 1 (ICAM), vascular cellular adhesion molecule (VCAM), and C-reactive protein (CRP). All participants were classified by fundus image grading on the basis of the eye with more severe AMD features.
   Main Outcome Measure: Neovascular AMD.
   Results: There were 195 participants with choroidal neovascularization in at least one eye, 97 nonneovascular AMD participants, and 115 controls (no drusen or pigmentary irregularities in either eye). In confounder-adjusted logistic regression, a history of cardiovascular disease was strongly associated with neovascular AMD (odds ratio [OR], 7.53; 95% confidence interval [CI], 2.78-20.41). Cigarette smoking (OR, 3.71; 95% CI, 1.25-11.06), being in the highest quartile of body mass index (OR, 3.82; 95% CI, 1.22-12.01), stage 2 hypertension (OR, 3.21; 95% CI, 1.14-8.98), and being in the highest quartile of serum cholesterol (OR, 4.66; 95% CI, 1.35-16.13) were positively associated with neovascular AMD. There was, no association between AMD status and serum CRP, ICAM, or VCAM.
   Conclusions: Our results suggest that cardiovascular disease plays an etiological role in the development of choroidal neovascularization in a proportion of older adults and highlight the importance of control of blood pressure and cholesterol, avoidance of smoking, and maintenance of a normal body weight.
C1 [Hogg, Ruth E.; Chakravarthy, Usha] Royal Grp Hosp, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North Ireland.
   [Woodside, Jayne V.; Gilchrist, Sarah E. C. M.; Graydon, Ryan] Ctr Populat Sci, Nutr & Metab Grp, Belfast, Antrim, North Ireland.
   [Fletcher, Astrid E.] London Sch Hyg & Trop Med, London WC1, England.
   [Chan, Wing; Knox, Angela; Cartmill, Barry; Chakravarthy, Usha] Royal Grp Hosp Trust, Ophthalmol Subdiv Head & Skeletal Div, Belfast, Antrim, North Ireland.
C3 University of London; London School of Hygiene & Tropical Medicine
RP Chakravarthy, U (通讯作者)，Royal Grp Hosp, Inst Clin Sci, Ctr Vis Sci, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland.
EM ruthhogg@hotmail.com; u.chakravarthy@qub.ac.uk
RI Hogg, Ruth E./ABC-9602-2020
OI Hogg, Ruth E./0000-0001-9413-2669; Woodside, Jayne/0000-0002-5691-4659;
   Chakravarthy, Usha/0000-0002-2606-3734
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NR 38
TC 108
Z9 110
U1 0
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUN
PY 2008
VL 115
IS 6
BP 1046
EP 1052
DI 10.1016/j.ophtha.2007.07.031
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 306XX
UT WOS:000256282800019
PM 17953990
DA 2022-11-30
ER

PT J
AU Kinose, F
   Roscilli, G
   Lamartina, S
   Anderson, KD
   Bonelli, F
   Spence, SG
   Ciliberto, G
   Vogt, TF
   Holder, DH
   Toniatti, C
   Thut, CJ
AF Kinose, F
   Roscilli, G
   Lamartina, S
   Anderson, KD
   Bonelli, F
   Spence, SG
   Ciliberto, G
   Vogt, TF
   Holder, DH
   Toniatti, C
   Thut, CJ
TI Inhibition of retinal and choroidal neovascularization by a novel KDR
   kinase inhibitor
SO MOLECULAR VISION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; PROLIFERATIVE DIABETIC-RETINOPATHY;
   OXYGEN-INDUCED RETINOPATHY; MACULAR DEGENERATION; CELLS; VEGF;
   EXPRESSION; RECEPTORS; ANGIOGENESIS; RAT
AB Purpose: Inhibition of vascular endothelial growth factor (VEGF) signaling has shown great promise for the treatment of ocular neovascular disease. Current anti-VEGF therapies in late-stage development, while efficacious, require dosing by frequent intravitreal injections that are inconvenient to patients. VEGF signaling inhibitors that demonstrate more convenient dosing regimens could lead to the improved treatment of neovascular diseases such as wet age related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR). Here we describe the assessment of a KDR (VEGFR2) kinase inhibitor in two well-established models of ocular neovascularization following oral administration.
   Methods: A novel KDR kinase inhibitor was dosed by oral gavage for 12 days at 0, 10, 30, or 100 mg/kg in an adult male Brown Norway rat laser induced choroidal neovascularization (CNV) model. The areas of CNV lesions were quantitated by fluorescence image analysis of FITC-dextran perfused animals. The kinase inhibitor was also assessed in a rat oxygen induced retinopathy (OIR) model in which neonatal rats were placed in an oxygen chamber that delivered alternating 24 h cycles of 50% and 10% oxygen for 14 days. After 14 days of oxygen treatment, the animals were returned to room air and dosed orally for 7 days with 0, 10, or 30 mg/kg kinase inhibitor. The extent of retinal neovascularization was assessed by counting pre-retinal neovascular nuclei on histological sections.
   Results: At doses of 100 mg/kg, the KDR kinase inhibitor resulted in a 98% reduction in lesion size in the rat CNV model. 30 mg/kg doses of the inhibitor showed a 70% and 80% reduction in lesion size in the laser CNV and OIR models, respectively.
   Conclusions: Oral dosing of the described KDR kinase inhibitor effectively inhibits neovascularization in two well-established animal models of ocular neovascularization. These data suggest that compounds of this class may prove to be useful for the treatment of a variety of ocular neovascular diseases using a convenient oral dosing regimen.
C1 Merck & Co Inc, Dept Ophthalm Res, W Point, PA 19486 USA.
   Merck & Co Inc, Dept Med Chem, W Point, PA 19486 USA.
   Merck & Co Inc, Dept Safety Assessment, W Point, PA 19486 USA.
   Merck & Co Inc, Dept Biometr Res, W Point, PA 19486 USA.
   Merck & Co Inc, Dept Biochem, IRBM, Rome, Italy.
   Merck & Co Inc, Dept Pharmacol, IRBM, Rome, Italy.
   Merck & Co Inc, Dept Mol & Cellular Biol, IRBM, Rome, Italy.
   Merck & Co Inc, Dept Mol Profiling, Rahway, NJ 07065 USA.
C3 Merck & Company; Merck & Company; Merck & Company; Merck & Company;
   Merck & Company; Merck & Company; Merck & Company; Merck & Company
RP Thut, CJ (通讯作者)，Merck & Co Inc, Dept Ophthalm Res, 770 Sumneytown Pike,WP26A-2000, W Point, PA 19486 USA.
EM catherine_thut@merck.com
RI Ciliberto, Gennaro/J-4131-2017
OI Ciliberto, Gennaro/0000-0003-2851-8605; Toniatti,
   Carlo/0000-0001-9493-344X; Spence, Stan/0000-0001-8448-0862
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NR 43
TC 41
Z9 48
U1 0
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD MAY 27
PY 2005
VL 11
IS 43-44
BP 366
EP 373
PG 8
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 934AL
UT WOS:000229678800001
PM 15951738
DA 2022-11-30
ER

PT J
AU Teshome, T
   Melaku, S
   Bayu, S
AF Teshome, T
   Melaku, S
   Bayu, S
TI Pattern of retinal diseases at a teaching eye department, Addis Ababa,
   Ethiopia
SO ETHIOPIAN MEDICAL JOURNAL
LA English
DT Article
ID VEIN OCCLUSION; DIABETIC-RETINOPATHY; VISUAL IMPAIRMENT; DETACHMENT;
   BLINDNESS; PREVALENCE; COMPLICATIONS; EPIDEMIOLOGY; ASSOCIATIONS;
   AFRICAN
AB The purpose of this study was to evaluate the pattern of retinal diseases as seen at a teaching and tertiary eye care center in Addis Ababa. In a descriptive, cross-sectional study, all consecutive patients seen at the retina clinic of Menelik II Hospital during a 19 months period (January 2000 to August 2001) were included in this series. Pertinent demographic and clinical data were recorded for all patients. A total of 1390 new patients with retinal diseases were seen at the retina clinic during the study period, accounting for 12.5% of the total outpatient population of the eye department. The male to female ratio was 1.8:1. The mean age was 45.2 years +/- 17.3years (range 2 months to 92 years) and median of 44.5 years. Two hundred and twenty-four (16.1%) patients were bilaterally blind, 465 (33.5%) patients were unilaterally blind, 280 (20.1%) patients had bilateral visual impairment and 195 (14.0%) patients had unilateral visual impairment, while 213 (15.3%) patients had normal vision. Retinal detachment was the commonest cause of both bilateral (54.9%) and unilateral blindness (41.2%), while diabetic retinopathy and myopia were the leading causes of bilateral visual impairment accounting for 36.8% and 28.2% respectively. Retinal vascular diseases accounted for the largest group of patients (38.1%) of which diabetic retinopathy accounted for 75.1%. Retinal detachment was the second largest group of diseases, accounting for 24.5% of the total. The proportion of patients with age-related macular degeneration was only 2.7%. Most of the patients presented with advanced disease, which required vitreo-retinal surgery. There is a need to improve on the early diagnosis and early referral of retinal diseases at primary and secondary care levels. Selected tertiary care centers should develop capacity to provide laser and vitreo-retinal surgery. The introduction of posterior vitrectomy in Ethiopia is long overdue.
C1 Univ Addis Ababa, Dept Ophthalmol, Fac Med, Addis Ababa, Ethiopia.
C3 Addis Ababa University
RP Teshome, T (通讯作者)，Univ Addis Ababa, Dept Ophthalmol, Fac Med, Addis Ababa, Ethiopia.
RI Bayu, Samson/GQI-3307-2022
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NR 35
TC 10
Z9 10
U1 0
U2 0
PU ETHIOPIAN MED ASSN
PI ADDIS ABABA
PA P O BOX 2179, ADDIS ABABA, ETHIOPIA
SN 0014-1755
J9 ETHIOPIAN MED J
JI Ethiop. Med. J.
PD JUL
PY 2004
VL 42
IS 3
BP 185
EP 193
PG 9
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 875LH
UT WOS:000225421200005
PM 16895036
DA 2022-11-30
ER

PT J
AU Bascuas, T
   Kropp, M
   Harmening, N
   Wong, BM
   Johnen, S
   Izsvak, Z
   Thumann, G
AF Bascuas, Thais
   Kropp, Martina
   Harmening, Nina
   Wong, Brittany M.
   Johnen, Sandra
   Izsvak, Zsuzsanna
   Thumann, Gabriele
TI Isolation, Culture, and Genetic Engineering of Mammalian Primary Pigment
   Epithelial Cells for Non-Viral Gene Therapy
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
ID MACULAR DEGENERATION; BRUCHS MEMBRANE; CHOROID GRAFT; IRIS;
   TRANSPLANTATION; NEOVASCULARIZATION; TRANSLOCATION; SURVIVAL; REMOVAL;
   LAYERS
AB Age-related macular degeneration (AMD) is the most frequent cause of blindness in patients >60 years, affecting similar to 30 million people worldwide. AMD is a multifactorial disease influenced by environmental and genetic factors, which lead to functional impairment of the retina due to retinal pigment epithelial (RPE) cell degeneration followed by photoreceptor degradation. An ideal treatment would include the transplantation of healthy RPE cells secreting neuroprotective factors to prevent RPE cell death and photoreceptor degeneration. Due to the functional and genetic similarities and the possibility of a less invasive biopsy, the transplantation of iris pigment epithelial (IPE) cells was proposed as a substitute for the degenerated RPE. Secretion of neuroprotective factors by a low number of subretinally-transplanted cells can be achieved by Sleeping Beauty (SB100X) transposon-mediated transfection with genes coding for the pigment epithelium-derived factor (PEDF) and/or the granulocyte macrophage-colony stimulating factor (GM-CSF). We established the isolation, culture, and SB100X-mediated transfection of RPE and IPE cells from various species including rodents, pigs, and cattle. Globes are explanted and the cornea and lens are removed to access the iris and the retina. Using a custom-made spatula, IPE cells are removed from the isolated iris. To harvest RPE cells, a trypsin incubation may be required, depending on the species. Then, using RPE-customized spatula, cells are suspended in medium. After seeding, cells are monitored twice per week and, after reaching confluence, transfected by electroporation. Gene integration, expression, protein secretion, and function were confirmed by qPCR, WB, ELISA, immunofluorescence, and functional assays. Depending on the species, 30,000-5 million (RPE) and 10,000-1.5 million (IPE) cells can be isolated per eye. Genetically modified cells show significant PEDF/GM-CSF overexpression with the capacity to reduce oxidative stress and offers a flexible system for ex vivo analyses and in vivo studies transferable to humans to develop ocular gene therapy approaches.
C1 [Bascuas, Thais; Kropp, Martina; Harmening, Nina; Wong, Brittany M.; Thumann, Gabriele] Univ Geneva, Expt Ophthalmol, Geneva, Switzerland.
   [Bascuas, Thais; Kropp, Martina; Harmening, Nina; Thumann, Gabriele] Univ Hosp Geneva, Dept Ophthalmol, Geneva, Switzerland.
   [Johnen, Sandra] Univ Hosp RWTH Aachen, Dept Ophthalmol, Aachen, Germany.
   [Izsvak, Zsuzsanna] Max Delbruck Ctr Mol Med, Berlin, Germany.
C3 University of Geneva; University of Geneva; RWTH Aachen University; RWTH
   Aachen University Hospital; Helmholtz Association; Max Delbruck Center
   for Molecular Medicine
RP Bascuas, T; Kropp, M (通讯作者)，Univ Geneva, Expt Ophthalmol, Geneva, Switzerland.; Bascuas, T; Kropp, M (通讯作者)，Univ Hosp Geneva, Dept Ophthalmol, Geneva, Switzerland.
EM thais.bascuascastillo@unige.ch; martina.kropp@unige.ch
RI Johnen, Sandra/ABA-9955-2020
OI Johnen, Sandra/0000-0003-0028-2557; Wong, Brittany/0000-0002-0837-8492
FU European Commission; Swiss National Sciences Foundation;
   Schmieder-Bohrisch Foundation; European Research Council, ERC
   [ERC-2011-ADG 294742]; Fulbright Research Grant; Swiss Government
   Excellence Scholarship
FX A thank deserves to Gregg Sealy and Alain Conti for their excellent
   technical assistance. This work was supported by the European Commission
   in the context of the Seventh Framework Programme, the Swiss National
   Sciences Foundation, and the Schmieder-Bohrisch Foundation. Z.I.
   received funding from the European Research Council, ERC Advanced
   [ERC-2011-ADG 294742] and B.M.W. from a Fulbright Research Grant and
   Swiss Government Excellence Scholarship.
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NR 47
TC 1
Z9 1
U1 0
U2 3
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD FEB
PY 2021
IS 168
AR e62145
DI 10.3791/62145
PG 21
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA RV9XN
UT WOS:000646178300076
PM 33720134
DA 2022-11-30
ER

PT J
AU Hecht, A
   Pollreisz, A
   Sayegh, R
   Told, R
   Baratsits, M
   Baumann, B
   Pircher, M
   Hitzenberger, CK
   Sacu, S
   Schmidt-Erfurth, U
AF Hecht, Alexander
   Pollreisz, Andreas
   Sayegh, Ramzi
   Told, Reinhard
   Baratsits, Magdalena
   Baumann, Bernhard
   Pircher, Michael
   Hitzenberger, Christoph K.
   Sacu, Stefan
   Schmidt-Erfurth, Ursula
TI Relationship between morphological and vascular alterations in
   geographic atrophy using a multimodal imaging approach
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; choriocapillaris; geographic atrophy;
   multimodal imaging; optical coherence tomography; optical coherence
   tomography angiography; retinal pigment epithelium
ID OPTICAL COHERENCE TOMOGRAPHY; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; IN-VIVO; CHORIOCAPILLARIS; EYES; SPEED; RPE;
   AUTOFLUORESCENCE; FLUORESCENCE
AB Purpose To assess geographic atrophy (GA) using a multimodal imaging approach, focusing on alterations at the level of the retinal pigment epithelium (RPE) and the choriocapillaris (CC) layers, by lesion demarcation, and assessment of morphological alterations within the atrophic area and in the transition zone.
   Methods Fifty-seven eyes of 34 patients with atrophic age-related macular degeneration (AMD) were included in this prospective, observational, cross-sectional study. Multimodal imaging using wide-field polarization-sensitive optical coherence tomography (PS-OCT), optical coherence tomography angiography (OCT-A) and fundus autofluorescence (FAF) was performed. The images were overlaid and used to analyse and compare alterations in the retina and the CC.
   Results Mean atrophic lesion size was 8.15 mm(2) (range: 2.23-17.23 mm(2)). In 52 of 57 eyes (91%), OCT-A displayed focal hypodense areas at the CC level in the transition zone of GA, as well as increased focal depolarizing material (e.g. melanin-containing structures) showed in PS-OCT en face depolarizing material maps. These regions of increased depolarizing material at the transition zone corresponded to the hypodense areas on OCT-A scans. All 57 eyes presented with abnormal FAF patterns at the transition zone. All 57 eyes showed distinct alterations of CC flow pattern architecture. Six eyes (11%) demonstrated reduced and three eyes (5%) a complete loss of CC flow pattern architecture across the entire area of GA, while 48 of 57 eyes (84%) presented with irregular mixed patterns of different focal alterations of CC flow architecture within the area of GA. Reduced CC patterns exceeding GA lesion margins into the transitional zone were found in all eyes.
   Conclusions Optical coherence tomography angiography images revealed different degrees of flow impairment within the atrophic lesion area and its transition zone. Alterations in RPE morphology and tissue integrity resulting in accumulation of depolarizing material, such as melanin, could result in misinterpretation of OCT-A imaging in areas in the shadow of depolarizing material. These changes seem to be partially independent from autofluorescence altering processes.
C1 [Hecht, Alexander; Pollreisz, Andreas; Sayegh, Ramzi; Told, Reinhard; Sacu, Stefan; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
   [Hecht, Alexander; Baratsits, Magdalena; Sacu, Stefan] Med Univ Vienna, Vienna Clin Trial Ctr, Dept Ophthalmol, Vienna, Austria.
   [Baumann, Bernhard; Pircher, Michael; Hitzenberger, Christoph K.] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna; Medical
   University of Vienna
RP Sacu, S (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM stefan.sacu@meduniwien.ac.at
RI Pollreisz, Andreas/AAJ-1538-2021
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311; Told,
   Reinhard/0000-0003-2046-7081
FU Canon Inc Funding Source: Medline
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NR 37
TC 1
Z9 1
U1 1
U2 3
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD SEP
PY 2020
VL 98
IS 6
BP E700
EP E708
DI 10.1111/aos.14352
EA FEB 2020
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA NC0UA
UT WOS:000513856500001
PM 32067383
OA hybrid
DA 2022-11-30
ER

PT J
AU Pi, JJ
   Cheng, Y
   Sun, HM
   Chen, XL
   Zhuang, T
   Liu, J
   Li, YX
   Chang, H
   Zhang, L
   Zhang, YZ
   Tao, T
AF Pi, Jingjiang
   Cheng, Yu
   Sun, Huimin
   Chen, Xiaoli
   Zhuang, Tao
   Liu, Jie
   Li, Yixi
   Chang, Huan
   Zhang, Lin
   Zhang, YuZhen
   Tao, Ting
TI Apln-CreERT:mT/mG reporter mice as a tool for sprouting angiogenesis
   study
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Retina; Sprouting angiogenesis; Membrane tomato red (mT); Membrane GFP
   (mG); Apelin
ID IN-VIVO; EXPRESSION; HYPOXIA; MOUSE; VASCULATURE; RETINOPATHY; ARTERIES;
   CANCER; MODEL
AB Background: Angiogenesis is defined as a new blood vessel sprouting from pre-existing vessels, and the sprouting angiogenesis is the start phase of angiogenesis, which is critical for both physiological and pathological processes, such as embryonic development, organ growth, wound healing, tumor growth, diabetic retinopathy and age-related macular degeneration. Better understanding of the mechanisms of sprout angiogenesis will provide a rationale for the treatments of these angiogenesis related diseases.
   Methods: mT/mG tool mice are crossed with Apln-CreERT mice to generate Apln-CreERT:mT/mG mice, then we used neonatal retinal angiogenesis model to observe the angiogenic pattern of Apln-CreERT:mT/mG mice compared with Cdh5-CreERT:mT/mG mice. FACS analysis was used to sort eGFP and tdTomato endothelial cells (ECs) for measuring Apelin and Cdh5 expression. Retinal sprouting angiogenesis pattern was also observed at different neonatal time when induced by tamoxifen and at hypoxia condition, as well as in vivo tumor in real-time angiogenesis in a dorsal skinfold window chamber in Apln-CreERT:mT/mG mice.
   Results: Apln-CreERT:mT/mG mice exhibited eGFP signal only in the sprouting angiogenesis, with less eGFP expression in the retinal "optic nerve" area than in that of Cdh5-CreERT:mT/mG mice, which might be due to relative mature vessels in the "optic nerve" area. The ECs sorted by FACS confirmed that the Apelin expression level was higher in eGFP ECs than tdTomato ECs of "optic nerve" area. Further we found that GFP-labeled sprouting angiogenesis decreased gradually following tamoxifen administration from P5-P7, but increased significantly during hypoxia in Apln-CreERT:mT/mG mice. At last, using Apln-CreERT:mT/mG mice we found tumor sprouting angiogenesis in dorsal skinfold, but not in the normal skinfold tissue.
   Conclusions: Apln-CreERT:mT/mG mouse line is a useful tool to differentiate sprouting angiogenesis from whole blood vessels in the investigation of retinal and tumor sprouting angiogenesis in vivo.
C1 [Pi, Jingjiang; Sun, Huimin; Chen, Xiaoli; Zhuang, Tao; Liu, Jie; Li, Yixi; Chang, Huan; Zhang, Lin; Zhang, YuZhen] Tongji Univ, Sch Med, Shanghai East Hosp, Minist Educ China,Res Ctr Translat Med,Key Lab Ar, Shanghai 200120, Peoples R China.
   [Cheng, Yu] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Ophthalmol, 197 Ruijin Er Rd, Shanghai 200025, Peoples R China.
   [Li, Yixi; Chang, Huan] Dalian Med Univ, Dalian 116044, Liaoning, Peoples R China.
   [Tao, Ting] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Geriatr, Sch Med, 197 Ruijin Er Rd, Shanghai 200025, Peoples R China.
C3 Ministry of Education, China; Tongji University; Shanghai Jiao Tong
   University; Dalian Medical University; Shanghai Jiao Tong University
RP Tao, T (通讯作者)，Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Geriatr, Sch Med, 197 Ruijin Er Rd, Shanghai 200025, Peoples R China.
EM tt10889@rjh.com.cn
FU Ministry of Science and Technology of National Natural Science
   Foundation of China [91,639,112, 81,470,472, 81,670,234, 81,370,433,
   81,470,393]; Ministry of Science and Technology of People's Republic of
   China [2012CB966803]
FX The study was supported by funds from the Ministry of Science and
   Technology of the National Natural Science Foundation of China
   (91,639,112, 81,470,472, 81,670,234, 81,370,433 and 81,470,393),
   Ministry of Science and Technology of People's Republic of China
   (2012CB966803).
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NR 31
TC 7
Z9 7
U1 2
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD SEP 2
PY 2017
VL 17
AR 163
DI 10.1186/s12886-017-0556-6
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FF6SZ
UT WOS:000409148600002
PM 28865439
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Govindaraju, VK
   Bodas, M
   Vij, N
AF Govindaraju, Viren Kumar
   Bodas, Manish
   Vij, Neeraj
TI Cigarette smoke induced autophagy-impairment regulates AMD pathogenesis
   mechanisms in ARPE-19 cells
SO PLOS ONE
LA English
DT Article
ID UBIQUITIN-PROTEASOME PATHWAY; PIGMENTED EPITHELIAL-CELLS; MACULAR
   DEGENERATION; OXIDATIVE-STRESS; EMPHYSEMA PATHOGENESIS; THERAPEUTIC
   STRATEGIES; PROTEIN AGGREGATION; SENESCENCE; EXPOSURE; DISEASES
AB Age related macular degeneration ( AMD) is one of the leading causes of blindness. Genetics, environmental insult, and age-related factors all play a key role in altering proteostasis, the homeostatic process regulating protein synthesis, degradation and processing. These factors also play a role in the pathogenesis of AMD and it has been well established that cigarette smoking (CS) initiates AMD pathogenic mechanisms. The primary goal of this study is to elucidate whether CS can induce proteostasis/autophagy-impairment in retinal pigment epithelial (RPE) cells. In our preliminary analysis, it was found that cigarette smoke extract (CSE) induces accumulation of ubiquitinated proteins in the insoluble protein fraction (p < 0.01), which was subsequently mitigated through cysteamine (p < 0.01) or fisetin (p < 0.05) treatment. Further, it was verified that these CSE induced ubiquitinated proteins accumulated in the peri-nuclear spaces (p < 0.05) that were cleared-off with cysteamine (p < 0.05) or fisetin (p < 0.05). Moreover, CSE-induced aggresome-formation (LC3B-GFP and Ub-RFP co-localization) and autophagy-flux impairment was significantly (p < 0.01) mitigated by cysteamine (p < 0.05) or fisetin (p < 0.05) treatment, indicating the restoration of CSE-mediated autophagy-impairment. CSE treatment was also found to induce intracellular reactive oxygen species (ROS, p < 0.001) while impacting cell viability (p < 0.001), which was quantified using CMH(2)DCFDA-dye (ROS) and MTS (proliferation) or propodium iodide staining (cell viability) assays, respectively. Moreover, cysteamine and fisetin treatment ameliorated CS-mediated ROS production (p < 0.05) and diminished cell viability (p < 0.05). Lastly, CSE was found to induce cellular senescence (p < 0.001), which was significantly ameliorated by cysteamine (p < 0.001) or fisetin (p < 0.001). In conclusion, our study indicates that CS induced proteostasis/autophagy-impairment regulates mechanisms associated with AMD pathogenesis. Moreover, autophagy-inducing drugs such as cysteamine or fisetin can ameliorate AMD pathogenesis mechanisms that warrant further investigation in pre-clinical murine models.
C1 [Govindaraju, Viren Kumar; Bodas, Manish; Vij, Neeraj] Cent Michigan Univ, Coll Med, Mt Pleasant, MI 48859 USA.
   [Vij, Neeraj] Johns Hopkins Univ, Sch Med, Dept Pediat & Pulm Med, Baltimore, MD 21218 USA.
C3 Central Michigan University; Johns Hopkins University
RP Vij, N (通讯作者)，Cent Michigan Univ, Coll Med, Mt Pleasant, MI 48859 USA.; Vij, N (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Pediat & Pulm Med, Baltimore, MD 21218 USA.
EM neeraj.vij@cmich.edu
RI Bodas, Manish/AAE-4016-2020
OI Bodas, Manish/0000-0002-1046-9799
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NR 47
TC 8
Z9 9
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 2
PY 2017
VL 12
IS 8
AR e0182420
DI 10.1371/journal.pone.0182420
PG 17
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FC3VT
UT WOS:000406768200081
PM 28767736
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Coscas, G
   Lupidi, M
   Coscas, F
   Francais, C
   Cagini, C
   Souied, EH
AF Coscas, Gabriel
   Lupidi, Marco
   Coscas, Florence
   Francais, Catherine
   Cagini, Carlo
   Souied, Eric H.
TI Optical Coherence Tomography Angiography during Follow-Up: Qualitative
   and Quantitative Analysis of Mixed Type I and II Choroidal
   Neovascularization after Vascular Endothelial Growth Factor Trap Therapy
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Optical coherence tomography angiography; Amplitude decorrelation
   angiography; Choroidal neovascularization; Exudative age-related macular
   degeneration; Multimodal imaging
ID FLUORESCEIN ANGIOGRAPHY; MACULAR DEGENERATION; HISTORY
AB Purpose: To report the optical coherence tomography angiography (OCT-A) findings in an exudative age-related macular degeneration (AMD) patient presenting mixed type I and II choroidal neovascularization (CNV) during follow-up after intravitreal vascular endothelial growth factor (VEGF) trap treatment. Methods: The clinical assessment included both traditional multimodal imaging, based on fluorescein angiography (FA), indocyanine green angiography (ICGA) and B-scan OCT, and OCT-A at baseline and follow-up. OCT-A images were obtained using a Spectralis OCT-A prototype able to acquire 70,000 A-scans per second, with a resolution of 7 mu m axially and 14 mu m laterally. An amplitude decorrelation algorithm developed by Heidelberg Engineering was applied to a volume scan, on a 15 x 5 degrees area, which was com- posed of 131 B-scans (35 frames per scan) at a distance of 11 mu m each. The borders of type I and type II CNV were manually outlined and then the areas were analyzed using the provided automated software before and after treatment. Results: The qualitative approach revealed a substantial decrease in the visibility of tiny branching vessels and anastomoses both in type I and type II components of the neovascular complex, associated with persistence of a clear hyperintense signal coming from the larger trunks, which remained well-perfused. Quantitative analysis confirmed a reduction of the lesion area after VEGF trap treatment: the type II component decreased from 0.25 to 0.19 mm(2), while the type I component decreased from 2.03 to 1.80 mm(2). Conclusions: Our study qualitatively and quantitatively demonstrated the response of a mixed type I-II CNV to intravitreal VEGF trap therapy. Although FA remains the gold standard for determining the presence of leakage and OCT easily shows fluid accumulation and its variations, OCT-A offers noninvasive monitoring of the retinal and choriocapillaris microvasculature in patients with CNV, aiding in diagnosis and treatment decisions during follow-up. (C) 2015 S. Karger AG, Basel
C1 [Coscas, Gabriel; Lupidi, Marco; Coscas, Florence; Francais, Catherine] Ctr Odeon, Paris, France.
   [Coscas, Gabriel; Coscas, Florence; Souied, Eric H.] Univ Paris Est, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, Creteil, France.
   [Lupidi, Marco; Cagini, Carlo] Univ Perugia, Dept Biomed & Surg Sci, Sect Ophthalmol, S Maria Misericordia Hosp, I-06100 Perugia, Italy.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil;
   University of Perugia
RP Coscas, G (通讯作者)，Ctr Hosp Intercommunal Creteil, 40 Ave Verdun, FR-94000 Creteil, France.
EM gabriel.coscas@gmail.com
RI Cagini, Carlo/H-3431-2019; Cagini, Carlo/L-2914-2016
OI Cagini, Carlo/0000-0002-3812-9219; Cagini, Carlo/0000-0002-3812-9219;
   Lupidi, Marco/0000-0002-6817-2488
CR Ambati J, 2003, SURV OPHTHALMOL, V48, P257, DOI 10.1016/S0039-6257(03)00030-4
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NR 22
TC 75
Z9 84
U1 0
U2 9
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2015
VL 54
IS 2
BP 57
EP 63
DI 10.1159/000433547
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CQ9KQ
UT WOS:000360933800001
PM 26201877
DA 2022-11-30
ER

PT J
AU Jefferis, JM
   Taylor, JP
   Collerton, J
   Jagger, C
   Kingston, A
   Davies, K
   Kirkwood, T
   Clarke, MP
AF Jefferis, Joanna M.
   Taylor, John-Paul
   Collerton, Joanna
   Jagger, Carol
   Kingston, Andrew
   Davies, Karen
   Kirkwood, Tom
   Clarke, Michael P.
TI The Association between Diagnosed Glaucoma and Cataract and Cognitive
   Performance in very old People: Cross-sectional Findings from the
   Newcastle 85+ Study
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Cataract; cognitive impairment; dementia; elderly; glaucoma; Newcastle;
   85+; older people
ID BLUE MOUNTAINS EYE; MINI-MENTAL-STATE; OPEN-ANGLE GLAUCOMA;
   ALZHEIMERS-DISEASE; RISK-FACTORS; DEMENTIA; IMPAIRMENT; PREVALENCE;
   AUSTRALIA; SURGERY
AB Purpose: Common age-related eye diseases including glaucoma, cataract and age-related macular degeneration (AMD) have been proposed to be associated with dementia. Few studies have examined the relationship between cognition and cataract or glaucoma. We explored the association between cognition and cataract and glaucoma diagnoses in community-dwelling 85-year-olds.
   Methods: Cross-sectional analysis of data from the Newcastle 85+ Study. Diagnoses of eye disease were extracted from family practice records. Cognitive performance was assessed by the standardized mini-mental state examination (sMMSE) and the sMMSE-blind (MMblind). Relationships between glaucoma diagnosis or cataract diagnosis and lower cognition were examined using ordinal logistic regression.
   Results: Complete data were available for 839 participants. Of these, 36.0% (302/839) had recorded previous cataract surgery, 11.2% (94/839) untreated cataract and 7.9% (66/839) diagnosed glaucoma. Glaucoma diagnosis was associated with lower sMMSE results (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.05-2.95); but not lower MMblind (OR 1.17, 95% CI 0.65-2.12). When compared to no cataract, cataract diagnosis (treated and untreated combined) was associated with higher sMMSE (OR 0.55, 95% CI 0.38-0.79) and MMblind (OR 0.51, 95% CI 0.34-0.76). Previously treated cataract was associated with higher sMMSE (OR 0.72, 95% CI 0.59-0.88) and MMblind (OR 0.68, 95% CI 0.55-0.85). Untreated cataract was not significantly associated with sMMSE (OR 0.65, 95% CI 0.36-1.19) or MMblind (OR 0.73, 95% CI 0.39-1.36).
   Conclusions: This large epidemiological study of 85-year-olds found that lower sMMSE but not MMblind was associated with glaucoma diagnosis, suggesting the association may be driven by poor vision. Cataract diagnosis was associated with higher sMMSE and MMblind. Reasons for this observation are unclear but may relate to enhanced help-seeking behavior in people with diagnosed cataract.
C1 [Jefferis, Joanna M.; Taylor, John-Paul; Collerton, Joanna; Jagger, Carol; Kingston, Andrew; Davies, Karen; Kirkwood, Tom] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England.
   [Jefferis, Joanna M.; Clarke, Michael P.] Royal Victoria Infirm, Dept Ophthalmol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
C3 Newcastle University - UK; Newcastle University - UK
RP Jefferis, JM (通讯作者)，Newcastle Univ, Clin & Ageing Res Unit, Campus Ageing & Vital, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England.
EM joanna.jefferis@ncl.ac.uk
RI Taylor, John Paul/D-1480-2009
OI Taylor, John Paul/0000-0001-7958-6558; Jagger,
   Carol/0000-0002-6377-9926; Davies, Karen/0000-0002-2820-9397; Kingston,
   Andrew/0000-0003-4211-7007
FU Medical Research Council; Biotechnology and Biological Sciences Research
   Council [G0500997]; National Institute of Health Research (NIHR)
   [2010-03-071]; UK NIHR Biomedical Research Centre for Ageing and
   Age-Related Disease award; Medical Research Council [G0500997,
   G0700718B] Funding Source: researchfish; National Institute for Health
   Research [ACF-2008-01-014, NF-SI-0508-10260] Funding Source:
   researchfish; MRC [G0500997] Funding Source: UKRI
FX This work was supported by a combined grant from the Medical Research
   Council and Biotechnology and Biological Sciences Research Council
   (grant number G0500997); the National Institute of Health Research
   (NIHR) (Doctoral Research Fellowship 2010-03-071 to JJ); and the UK NIHR
   Biomedical Research Centre for Ageing and Age-Related Disease award to
   the Newcastle upon Tyne Hospitals National Health Service Foundation
   Trust.
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NR 47
TC 23
Z9 23
U1 0
U2 8
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0928-6586
EI 1744-5086
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD APR
PY 2013
VL 20
IS 2
BP 82
EP 88
DI 10.3109/09286586.2012.757626
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 110BZ
UT WOS:000316418400002
PM 23510311
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Lee, MY
   Yoon, J
   Ham, DI
AF Lee, Mee Yon
   Yoon, Jaemoon
   Ham, Don-Il
TI Clinical Characteristics of Reticular Pseudodrusen in Korean Patients
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID SUBRETINAL DRUSENOID DEPOSITS; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; GRADING SYSTEM;
   RISK-FACTORS; PREVALENCE
AB PURPOSE: To clarify the clinical characteristics of reticular pseudodrusen in Korean patients.
   DESIGN: Retrospective, observational, consecutive case series.
   METHODS: A total of 255 eyes of 130 patients diagnosed with reticular pseudodrusen were evaluated. Reticular pseudodrusen were diagnosed by characteristic fundus findings using ophthalmoscopy, color fundus photography with blue-channel examination, near-infrared photography, red-free photography, autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography. Age-related macular degeneration (AMD) was determined by the International Classification and Grading System.
   RESULTS: The mean age was 72.6 +/- 9.0 years (range, 43 to 92 years). Most reticular pseudodrusen patients had bilateral disease (97.7%), with a female preponderance (86.2%). All 3 patients who showed unilateral reticular pseudodrusen had neovascular AMD in the eye with no reticular pseudodrusen. AMD was found in 183 eyes (71.8 %), among which early AMD was found in 115 eyes (45.1%), geographic atrophy was found in 41 eyes (16.1%), and neovascular AMD was found in 27 eyes (10.6%). The mean age of patients with AMD and with no AMD was 73.7 +/- 9.2 years (range, 58 to 92 years) and 69.9 +/- 11.7 years (range, 43 to 90 years), respectively, and there was a statistical difference between these 2 groups (P < .05). Classic choroidal neovascularization was found in 13 eyes (48.1%), and occult choroidal neovascularization was found in 14 eyes (51.9%) in the neovascular AMD group.
   CONCLUSIONS: Reticular pseudodrusen occurs in Koreans, and clinical manifestations of reticular pseudodrusen in Koreans did not differ significantly from those described in white persons. However, our study demonstrated a higher rate of bilaterality compared with those previously reported, and geographic atrophy was found to be associated more commonly with reticular pseudodrusen than with neovascular AMD. Ethnical differences may be associated with these findings, and further studies are required. (Am J Ophthalmol 2012;153:530-535. (C) 2012 by Elsevier Inc. All rights reserved.)
C1 [Lee, Mee Yon; Yoon, Jaemoon; Ham, Don-Il] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul 135710, South Korea.
C3 Sungkyunkwan University (SKKU); Samsung Medical Center
RP Ham, DI (通讯作者)，Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, 50 Ilwondong, Seoul 135710, South Korea.
EM oculus@naver.com
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   Smith RT, 2009, AM J OPHTHALMOL, V148, P733, DOI 10.1016/j.ajo.2009.06.028
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NR 21
TC 49
Z9 51
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD MAR
PY 2012
VL 153
IS 3
BP 530
EP 535
DI 10.1016/j.ajo.2011.08.012
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 907CB
UT WOS:000301394300019
PM 21996310
DA 2022-11-30
ER

PT J
AU Yoshikawa, T
   Ogata, N
   Izuta, H
   Shimazawa, M
   Hara, H
   Takahashi, K
AF Yoshikawa, Tadanobu
   Ogata, Nahoko
   Izuta, Hiroshi
   Shimazawa, Masamitsu
   Hara, Hideaki
   Takahashi, Kanji
TI Increased Expression of Tight Junctions in ARPE-19 Cells Under
   Endoplasmic Reticulum Stress
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Endoplasmic reticulum (ER) stress; Tight junction; Age-related macular
   degeneration (AMD); Retinal pigment epithelium (RPE); Transepithelial
   electrical resistance (TER)
ID UNFOLDED PROTEIN RESPONSE; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; ER STRESS; MOLECULAR CHAPERONES; DIABETIC-RETINOPATHY;
   ALZHEIMERS-DISEASE; ENDOTHELIAL-CELLS; QUALITY-CONTROL; GROWTH-FACTOR
AB Purpose: To investigate the effects of endoplasmic reticulum (ER) stress on the tight junctions of the retinal pigment epithelial (RPE) cells in vitro.
   Materials and Methods: ER stress was induced in cultured ARPE-19 cells, a human RPE cell line, by exposure to tunicamycin (TM) or to thapsigargin (TG). After 6, 12, 24 and 48 hours of exposure, the expressions of GRP78/Bip (Bip), C/EBP-homologous protein (CHOP), vascular endothelial growth factor (VEGF), zonula occludens (ZO)-1, occludin and claudin-1 were determined by real-time RT-PCR. Immunoblot analysis and/or immunohistochemistry for proteins of tight junctions and ER stress markers, viz., Bip, activating transcription factor (ATF) 6, CHOP, and caspase-4, were performed at 48 hours after the exposure. Enzyme-linked immunosorbent assay was used to determine the concentration of VEGF165. Transepithelial electrical resistance (TER) of the ARPE-19 cells was determined to measure the permeability.
   Results: The expressions of the mRNAs and/or proteins of Bip, CHOP, ATF6 and caspase-4 were significantly increased in ARPE-19 cells under ER stress induced by TM and TG. The mRNAs of VEGF were also increased by both TM and TG. However, the concentration of VEGF165 was not significantly increased after 48 hours exposure to TM and TG compared to that of the control in the apical chamber medium. The proteins and mRNAs of occludin and claudin-1 were significantly increased by TM and TG, and that of ZO-1 was significantly increased by TG. Immunohistochemistry showed that the staining of ZO-1, occludin and claudin-1 under ER stress was stronger than that of the control. A significant increase of TER was observed after exposure to TM and TG.
   Conclusions: The increased expressions of tight junction molecules by TM- or TG-exposed ARPE-19 cells indicate that ER stress can alter the function of RPE cells and may be involved in the pathogenesis of age-related macular degeneration.
C1 [Ogata, Nahoko] Nara Med Univ, Dept Ophthalmol, Kashihara, Nara 6348522, Japan.
   [Yoshikawa, Tadanobu] Kansai Med Univ, Takii Hosp, Dept Ophthalmol, Osaka, Japan.
   [Izuta, Hiroshi; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat Mol Pharmacol, Gifu, Japan.
   [Takahashi, Kanji] Kansai Med Univ, Hirakata Hosp, Dept Ophthalmol, Osaka, Japan.
C3 Nara Medical University; Kansai Medical University; Gifu Pharmaceutical
   University; Kansai Medical University
RP Ogata, N (通讯作者)，Nara Med Univ, Dept Ophthalmol, 840 Shijo Cho, Kashihara, Nara 6348522, Japan.
EM ogata@takii.kmu.ac.jp
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NR 55
TC 28
Z9 28
U1 1
U2 15
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0271-3683
J9 CURR EYE RES
JI Curr. Eye Res.
PD DEC
PY 2011
VL 36
IS 12
BP 1153
EP 1163
DI 10.3109/02713683.2011.606592
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 847NR
UT WOS:000296980100011
PM 21978097
DA 2022-11-30
ER

PT J
AU Dong, X
   Li, ZR
   Wang, W
   Zhang, WJ
   Liu, SZ
   Zhang, XM
AF Dong, Xin
   Li, Zhongrui
   Wang, Wei
   Zhang, Wenjie
   Liu, Shuizhong
   Zhang, Xiaomei
TI Protective effect of canolol from oxidative stress-induced cell damage
   in ARPE-19 cells via an ERK mediated antioxidative pathway
SO MOLECULAR VISION
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; INDUCED APOPTOSIS; HEME OXYGENASE-1;
   GLUTATHIONE
AB Purpose: Oxidative stress damage to retinal pigment epithelial (RPE) cells is thought to play a critical role in the pathogenesis of age-related macular degeneration (AMD). This study was conducted to investigate the protective effect of canolol against oxidative stress-induced cell death in ARPE-19 cells and its underlying mechanism.
   Methods: ARPE-19 cells, a human retinal pigment epithelial cell line, were subjected to oxidative stress with 150 mu M t-butyl hydroxide (t-BH) in the presence/absence of canolol in different concentrations. Cell viabilities were monitored by a 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyl tetrazolium bromide (MTT) assay. The apoptosis was measured by flow cytometry using Annexin V-FITC and PI staining and intracellular reactive oxygen species (ROS) levels were measured by a fluorescence spectrophotometer. Gene expression of NF-E2-related factor (Nrf-2), heme oxygenase-1 (HO-1), catalase and glutathione S-transferase-pi (GST-pi) were measured by a reverse transcription polymerase chain reaction (RT-PCR) assay. Activation of the extracellular signal regulated kinase (ERK) protein was evaluated by western blot analysis.
   Results: Canolol showed relatively high safety for ARPE-19 cells and recovered the cell death caused by t-BH dose-dependently at a concentration of 50-200 mu M. Canolol also reduced t-BH-induced intracellular ROS generation and thus protected ARPE-19 cells from cell apoptosis. HO-1, catalase, GST-pi, and Nrf-2 were elevated in ARPE-19 cells after treatment with different concentrations of canolol for 24 h. Finally, canolol was found to activate extracellular signal regulated kinase (ERK) phosphorylation in ARPE-19 cells under the condition, with or without t-BH.
   Conclusions: Canolol protected ARPE-19 cells from t-BH-induced oxidative damage and the protective mechanism was associated, at least partly, with the upregulation (activation) of antioxidative enzymes, probably through an ERK mediated pathway. This suggests that canolol offers a remarkable protective effect against oxidative damage of RPE cells and may have a therapeutic effect on AMD and other oxidative stress-related retinal diseases.
C1 [Dong, Xin; Li, Zhongrui; Wang, Wei; Zhang, Wenjie; Liu, Shuizhong; Zhang, Xiaomei] Harbin Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Harbin 150001, Heilongjiang, Peoples R China.
C3 Harbin Medical University
RP Zhang, XM (通讯作者)，Harbin Med Univ, Dept Ophthalmol, Affiliated Hosp 1, 23 Youzheng St, Harbin 150001, Heilongjiang, Peoples R China.
EM zhangxm66@tom.com
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NR 31
TC 37
Z9 38
U1 0
U2 9
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUL 27
PY 2011
VL 17
IS 222
BP 2040
EP 2048
PG 9
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 807FN
UT WOS:000293881800001
PM 21850179
DA 2022-11-30
ER

PT J
AU Kam, JH
   Lenassi, E
   Jeffery, G
AF Kam, Jaimie Hoh
   Lenassi, Eva
   Jeffery, Glen
TI Viewing Ageing Eyes: Diverse Sites of Amyloid Beta Accumulation in the
   Ageing Mouse Retina and the Up-Regulation of Macrophages
SO PLOS ONE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; COMPLEMENT ACTIVATION; SUBRETINAL MICROGLIA;
   COGNITIVE IMPAIRMENT; ELECTRON-MICROSCOPE; ALZHEIMERS-DISEASE; PRECURSOR
   PROTEIN; PERIPHERAL-NERVE; A-BETA; DRUSEN
AB Background: Amyloid beta (A beta) accumulates in the ageing central nervous system and is associated with a number of age-related diseases, including age-related macular degeneration (AMD) in the eye. AMD is characterised by accumulation of extracellular deposits called drusen in which A beta is a key constituent. A beta activates the complement cascade and its deposition is associated with activated macrophages. So far, little is known about the quantitative measurements of A beta accumulation and definitions of its relative sites of ocular deposition in the normal ageing mouse.
   Methodology/Principal Findings: We have traced A beta accumulation quantitatively in the ageing mouse retina using immunohistochemistry and Western blot analysis. We reveal that it is not only deposited at Bruch's membrane and along blood vessels, but unexpectedly, it also coats photoreceptor outer segments. While A beta is present at all sites of deposition from 3 months of age, it increases markedly from 6 months onward. Progressive accumulation of deposits on outer segments was confirmed with scanning electron microscopy, revealing age-related changes in their morphology. Such progress of accumulation of A beta on photoreceptor outer segments with age was also confirmed in human retinae using immunohistochemistry. We also chart the macrophage response to increases in A beta showing up-regulation in their numbers using both confocal laser imaging of the eye in vivo followed by in vitro immunostaining. With age macrophages become bloated with cellular debris including A beta, however, their increasing numbers fail to stop A beta accumulation.
   Conclusions: Increasing A beta deposition in blood vessels and Bruch's membrane will impact upon retinal perfusion and clearance of cellular waste products from the outer retina, a region of very high metabolic activity. This accumulation of A beta may contribute to the 30% reduction of photoreceptors found throughout life and the shortening of those that remain. The coating of A beta on outer segments may also have an impact upon visual function with age.
C1 [Kam, Jaimie Hoh; Lenassi, Eva; Jeffery, Glen] UCL, Inst Ophthalmol, London, England.
   [Lenassi, Eva] Univ Med Ctr, Hosp Eye, Ljubljana, Slovenia.
C3 University of London; University College London; University Medical
   Centre Ljubljana
RP Kam, JH (通讯作者)，UCL, Inst Ophthalmol, London, England.
EM g.jeffery@ucl.ac.uk
FU Rosetrees Trust
FX Funding was received from Rosetrees Trust. The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 59
TC 93
Z9 93
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 1
PY 2010
VL 5
IS 10
AR e13127
DI 10.1371/journal.pone.0013127
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 656TI
UT WOS:000282359300021
PM 20957206
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Edwards, AO
   Lee, SJ
   Fridley, BL
   Tosakulwong, N
AF Edwards, Albert O.
   Lee, Sung J.
   Fridley, Brooke L.
   Tosakulwong, Nirubol
TI Density of Common Complex Ocular Traits in the Aging Eye: Analysis of
   Secondary Traits in Genome-Wide Association Studies
SO PLOS ONE
LA English
DT Article
AB Genetic association studies are identifying genetic risks for common complex ocular traits such as age-related macular degeneration (AMD). The subjects used for discovery of these loci have been largely from clinic-based, case-control studies. Typically, only the primary phenotype (e.g., AMD) being studied is systematically documented and other complex traits (e.g., affecting the eye) are largely ignored. The purpose of this study was to characterize these other or secondary complex ocular traits present in the cases and controls of clinic-based studies being used for genetic study of AMD. The records of 100 consecutive new patients (of any diagnosis) age 60 or older for which all traits affecting the eye had been recorded systematically were reviewed. The average patient had 3.5 distinct diagnoses. A subset of 10 complex traits was selected for further study because they were common and could be reliably diagnosed. The density of these 10 complex ocular traits increased by 0.017 log-traits/year (P = 0.03), ranging from a predicted 2.74 at age 60 to 4.45 at age 90. Trait-trait association was observed only between AMD and primary vitreomacular traction (P = 0.0009). Only 1% of subjects age 60 or older had no common complex traits affecting the eye. Extrapolations suggested that a study of 2000 similar subjects would have sufficient power to detect genetic association with an odds ratio of 2.0 or less for 4 of these 10 traits. In conclusion, the high prevalence of complex traits affecting the aging eye and the inherent biases in referral patterns leads to the potential for confounding by undocumented secondary traits within case-control studies. In addition to the primary trait, other common ocular phenotypes should be systematically documented in genetic association studies so that adjustments for potential trait-trait associations and other bias can be made and genetic risk variants identified in secondary analyses.
C1 [Edwards, Albert O.; Lee, Sung J.; Tosakulwong, Nirubol] Mayo Clin, Dept Ophthalmol, Rochester, MN 55905 USA.
   [Fridley, Brooke L.] Mayo Clin, Div Biostat, Rochester, MN USA.
C3 Mayo Clinic; Mayo Clinic
RP Edwards, AO (通讯作者)，Mayo Clin, Dept Ophthalmol, Rochester, MN 55905 USA.
EM edwardslab@mayo.edu
RI Fridley, Brooke L/D-8315-2015
OI Fridley, Brooke L/0000-0001-7739-7956
FU Foundation Fighting Blindness, Owing Mills, MD [EY014467]; American
   Health Assistance Foundation, Clarksburg, MD; Research to Prevent
   Blindness, New York, NY; Mayo Clinic Foundation; NATIONAL EYE INSTITUTE
   [R01EY014467] Funding Source: NIH RePORTER
FX The research was supported by EY014467, the Foundation Fighting
   Blindness, Owing Mills, MD, the American Health Assistance Foundation,
   Clarksburg, MD, unrestricted departmental grants from Research to
   Prevent Blindness, New York, NY, and the Mayo Clinic Foundation. The
   sole role of the sponsors was to provide funding.
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NR 67
TC 2
Z9 2
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 25
PY 2008
VL 3
IS 6
AR e2510
DI 10.1371/journal.pone.0002510
PG 7
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 406IK
UT WOS:000263288000029
PM 18575587
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Hirata, Y
   Nishlwaki, H
AF Hirata, Y
   Nishlwaki, H
TI The choroidal circulation assessed by laser-targeted anglography
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
ID ENTRAPPED CIS-BIS-NEODECANOATO-TRANS-R,R-1,2-DIAMINOCYCLOHEXANE
   PLATINUM(II); INDOCYANINE GREEN VIDEOANGIOGRAPHY; INCLUDING FLOW
   DETERMINATIONS; LIPOSOMAL-AMPHOTERICIN-B; BLOOD-FLOW; DYE DELIVERY;
   DOPPLER FLOWMETRY; NONINVASIVE VISUALIZATION; FLUORESCEIN ANGIOGRAPHY;
   INTRAOCULAR-PRESSURE
AB The choroid plays an important role in supplying nutrients to and removing waste products from the outer region of the retina. Abnormal choroidal blood flow can disrupt normal retinal function and lead to alterations in visual function. Visualization of the choriocapillaris in vivo is a great challenge to understanding its normal physiology and involvement in the disease process. Laser-targeted angiography (LTA) is a relatively new method used to visualize and analyze the choroidal circulation. Carboxyfluorescein (CF), encapsulated in heat-sensitive liposomes, is released locally in the choroid through the application of a heat beam provided by an infrared laser. Video angiograms are generated with excitation illumination provided by an argon laser. Obtained images are highly selective to the choriocapillaris and are sharply contrasted against underlying and overlying structures. The images can be obtained repetitively, during which period the circulating liposome concentration is sufficient to generate adequate angiograms. These high-quality images have revealed three distinct phases (filling, plateau, and draining) of the choriocapillaris, In the plateau phase, a cluster of lobules fed by a common arteriole has been uniformly illuminated. This defined Cluster area does not change in size while an infrared laser is continuously applied to the same spot, which demonstrates that each cluster is functionally independent and no physiological communication exists between them. Only in posterior regions do the angiograms demonstrate during the filling and draining phases that each lobule is filled from a central spot and drained along a peripheral ring, showing honeycomb flow patterns. The regional differences in choriocapillaris flow patterns revealed by LTA suggests that the choriocapillaris provides a more highly efficient system of outflow in posterior regions than in peripheral regions. LTA is useful in analyzing choroidal circulation in vivo and has the potential for clinical application in the future. Additionally, LTA has a unique capability to image choroidal neovascularization in animal models and it promises potential application in age-related macular degeneration (AMD). (c) 2005 Elsevier Ltd. All rights reserved.
C1 Kyoto Univ, Grad Sch Med, Dept Ophthalmol, Sakyo Ku, Kyoto 6068507, Japan.
C3 Kyoto University
RP Nishlwaki, H (通讯作者)，Kyoto Univ, Grad Sch Med, Dept Ophthalmol, Sakyo Ku, 54 Shogoinkawahara Cho, Kyoto 6068507, Japan.
EM nishiwak@kuhp.kyoto-u.ac.jp
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NR 81
TC 12
Z9 14
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD MAR
PY 2006
VL 25
IS 2
BP 129
EP 147
DI 10.1016/j.preteyeres.2005.08.001
PG 19
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 023ZP
UT WOS:000236165000001
PM 16226483
DA 2022-11-30
ER

PT J
AU Bourne, RRA
   Dineen, B
   Ali, SM
   Huq, DMN
   Johnson, GJ
AF Bourne, RRA
   Dineen, B
   Ali, SM
   Huq, DMN
   Johnson, GJ
TI The National Blindness and Low Vision Prevalence Survey of Bangladesh:
   Research ophthalmic epidemiology design, eye examination methodology and
   results of the pilot study
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE blindness; low vision; pilot study methodology; underdeveloped
   countries; Bangladesh
ID QUALITY-OF-LIFE; CATARACT
AB PURPOSE To describe the research design and eye examination protocol of The National Blindness and Low Vision Prevalence Survey of Bangladesh and to present the main results of the rural pilot study.
   METHODS A thorough description of the sampling strategy, eye examination protocol and operational definitions are presented. Multi-stage stratified (rural/urban) cluster random sampling, with probability proportional-to-size procedures, will be used for selection of a cross-sectional, nationally representative sample (112,900 subjects) of the population aged greater than or equal to30 years. Each subject will be tested for visual acuity, auto-refracted and undergo optic disc examination. Those with <6/12 visual acuity in either eye will be re-tested with their refractive correction, dilated and examined for anterior and posterior segment disease.
   A preliminary, separate rural pilot survey sample was conducted according to the eye examination procedures, with results reported herein.
   RESULTS Two-hundred-and-four (73.1%) Of 279 eligible subjects were examined for the rural pilot. Forty-eight persons had presenting visual acuity worse than 6/12 in either eye: The presenting visual acuity of the better eye was used to group the subjects into the following WHO categories (brackets enclose the number of subjects after refractive correction): Blind: 4 [4]; Visually impaired: 29 [14]; Sighted: 171 [186], of whom 3 [3] were unilaterally blind. Cataract was the main cause of visual acuity of less than 6/12, followed by refractive error, and age-related macular degeneration.
   CONCLUSIONS The pilot survey demonstrated that the proposed examination process for the main survey was both feasible and appropriate for the purposes of this study. Particular strengths of the pilot and subsequent main survey include the use of logMAR visual acuity testing and auto-refraction of all subjects. The pilot study reveals the burden of cataract and refractive error, which are two of the five diseases specifically targeted by the WHO global blindness initiative 'Vision 2020'.
C1 UCL, Inst Ophthalmol, Int Ctr Eye Hlth, Dept Epidemiol & Int Eye Hlth, London EC1V 9EL, England.
   Bangladesh Natl Council Blind, Natl Inst Ophthalmol, Dhaka, Bangladesh.
C3 University of London; London School of Hygiene & Tropical Medicine;
   University College London
RP Bourne, RRA (通讯作者)，UCL, Inst Ophthalmol, Int Ctr Eye Hlth, Dept Epidemiol & Int Eye Hlth, 11-43 Bath St, London EC1V 9EL, England.
EM rupert_bourne@hotmail.com
OI Dineen, Brendan/0000-0002-9619-8044
CR [Anonymous], 1997, HUM DEV REP 1997
   *BANGL BUR STAT, 1993, BANGL POP CENS 1991, V2
   *BANGL BUR STAT, 1997, STAT POCK BANGL 1997
   *BANGL BUR STAT, 1997, BANGL POP CENS 1991, V3
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   Dunn G., 1989, DESIGN ANAL RELIABIL
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   World Health Organization, 1997, WORLD HLTH REP 1996, P1
NR 20
TC 23
Z9 26
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0928-6586
EI 1744-5086
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD APR
PY 2002
VL 9
IS 2
BP 119
EP 132
DI 10.1076/opep.9.2.119.1520
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 606EY
UT WOS:000178722200004
PM 11821977
DA 2022-11-30
ER

PT J
AU Tsai, CH
   Hoang, LN
   Lin, CC
   Pan, LC
   Wu, CL
   Lin, IC
   Wang, PY
   Tseng, CL
AF Tsai, Cheng-Han
   Hoang, Le Ngoc
   Lin, Chun Che
   Pan, Liang-Chen
   Wu, Chiao-Li
   Lin, I-Chan
   Wang, Peng-Yuan
   Tseng, Ching-Li
TI Evaluation of Topical and Subconjunctival Injection of Hyaluronic
   Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye
SO PHARMACEUTICS
LA English
DT Article
DE posterior eye; hyaluronic acid; surface charges; nanoparticles; drug
   delivery; eyedrops; subconjunctival injection; retina
ID SEGMENT; RETINA
AB Posterior eye diseases, such as age-related macular degeneration and diabetic retinopathy, are difficult to treat due to ineffective drug delivery to affected areas. Intravitreal injection is the primary method for posterior eye drug delivery; however, it is usually accompanied by complications. Therefore, an effective and non-invasive method is required. Self-assembling nanoparticles (NPs) made from gelatin-epigallocatechin gallate (EGCG) were synthesized (GE) and surface-decorated with hyaluronic acid (HA) for drug delivery to the retinal/choroidal area. Different HA concentrations were used to prepare NPs with negative (GEH-) or positive (GEH+) surface charges. The size/zeta potential and morphology of the NPs were characterized by a dynamic light scattering (DLS) system and transmission electron microscope (TEM). The size/zeta potential of GEH+ NPs was 253.4 nm and 9.2 mV. The GEH- NPs were 390.0 nm and -35.9 mV, respectively. The cytotoxicity was tested by adult human retinal pigment epithelial cells (ARPE-19), with the results revealing that variant NPs were non-toxicity at 0.2-50 mu g/mL of EGCG, and that the highest amount of GEH+ NPs was accumulated in cells examined by flowcytometry. Topical delivery (eye drops) and subconjunctival injection (SCI) methods were used to evaluate the efficiency of NP delivery to the posterior eyes in a mouse model. Whole eyeball cryosections were used to trace the location of fluorescent NPs in the eyes. The area of fluorescent signal obtained in the posterior eyes treated with GEH+ NPs in both methods (eye drops: 6.89% and SCI: 14.55%) was the greatest when compared with other groups, especially higher than free dye solution (2.79%). In summary, GEH+ NPs can be transported to the retina by eye drops and SCI; in particular, eye drops are a noninvasive method. Furthermore, GEH+ NPs, characterized by a positive surface and HA decoration, could facilitate drug delivery to the posterior eye as a useful drug carrier.
C1 [Tsai, Cheng-Han; Hoang, Le Ngoc; Tseng, Ching-Li] Taipei Med Univ, Grad Inst Biomed Mat & Tissue Engn, Coll Biomed Engn, 250 Wu Hsing St, Taipei 11031, Taiwan.
   [Lin, Chun Che] Natl Taipei Univ Technol, Inst Organ & Polymer Mat, Taipei 106344, Taiwan.
   [Lin, Chun Che] Natl Taipei Univ Technol, Res & Dev Ctr Smart Text Technol, Taipei 106344, Taiwan.
   [Pan, Liang-Chen; Wu, Chiao-Li] Taipei Med Univ, Sch Biomed Engn, Coll Biomed Engn, 250 Wu Hsing St, Taipei 11031, Taiwan.
   [Lin, I-Chan] Taipei Med Univ, Shuang Ho Hosp, Dept Ophthalmol, New Taipei 23561, Taiwan.
   [Lin, I-Chan] Taipei Med Univ, Sch Med, Dept Ophthalmol, Coll Med, Taipei 11031, Taiwan.
   [Wang, Peng-Yuan] Wenzhou Med Univ, Inst Aging, Oujiang Lab, Key Lab Alzheimers Dis Zhejiang Prov, Wenzhou 325000, Peoples R China.
   [Wang, Peng-Yuan; Tseng, Ching-Li] Taipei Med Univ, Coll Biomed Engn, Int PhD Program Biomed Engn, Taipei 11031, Taiwan.
C3 Taipei Medical University; National Taipei University of Technology;
   National Taipei University of Technology; Taipei Medical University;
   Taipei Medical University; Shuang Ho Hospital; Taipei Medical
   University; Wenzhou Medical University; Taipei Medical University
RP Tseng, CL (通讯作者)，Taipei Med Univ, Grad Inst Biomed Mat & Tissue Engn, Coll Biomed Engn, 250 Wu Hsing St, Taipei 11031, Taiwan.; Wang, PY (通讯作者)，Wenzhou Med Univ, Inst Aging, Oujiang Lab, Key Lab Alzheimers Dis Zhejiang Prov, Wenzhou 325000, Peoples R China.; Wang, PY; Tseng, CL (通讯作者)，Taipei Med Univ, Coll Biomed Engn, Int PhD Program Biomed Engn, Taipei 11031, Taiwan.
EM joyo4180@gmail.com; lengochoang252@gmail.com;
   cclin0530@mail.ntut.edu.tw; b812107043@tmu.edu.tw;
   b812107032@tmu.edu.tw; ichanlin@gmail.com; py.wang@ojlab.ac.cn;
   chingli@tmu.edu.tw
OI Le, Ngoc Hoang/0000-0003-4778-3527; Tseng, Ching-Li/0000-0001-9446-4030
FU Ministry of Science and Technology, Taiwan [MOST 106-2628-E-038-001-MY3,
   MOST 110-2314-B-038-044-MY2]; National Health Research Institute, Taiwan
   [NHRI-EX111-10933SI]
FX This research was funded by grants from the Ministry of Science and
   Technology, Taiwan (MOST 106-2628-E-038-001-MY3, MOST
   110-2314-B-038-044-MY2). In addition, this research was partly funded by
   the integrated research grant in health and medical sciences from the
   National Health Research Institute, Taiwan (NHRI-EX111-10933SI).
CR Battaglia L, 2018, LIPID NANOCARRIERS FOR DRUG TARGETING, P269, DOI 10.1016/B978-0-12-813687-4.00007-4
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NR 38
TC 0
Z9 0
U1 9
U2 9
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1999-4923
J9 PHARMACEUTICS
JI Pharmaceutics
PD JUN
PY 2022
VL 14
IS 6
AR 1253
DI 10.3390/pharmaceutics14061253
PG 17
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 2N1QB
UT WOS:000818161600001
PM 35745825
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Ortiz, D
   Lawson, T
   Jarrett, R
   Ring, A
   Scoles, KL
   Hoverman, L
   Rocheford, E
   Karcher, DM
   Rocheford, T
AF Ortiz, Darwin
   Lawson, Tyler
   Jarrett, Rachel
   Ring, Ashley
   Scoles, Kailynn L.
   Hoverman, Lisa
   Rocheford, Evan
   Karcher, Darrin M.
   Rocheford, Torbert
TI Biofortified orange corn increases xanthophyll density and yolk
   pigmentation in egg yolks from laying hens
SO POULTRY SCIENCE
LA English
DT Article
DE orange corn; macular carotenoids; yolk color; eggs; laying hens
ID ALZHEIMERS-DISEASE; CAROTENOIDS; IDENTIFICATION; PREVENTION; RETINOIDS;
   QUANTIFICATION; DEPOSITION; ZEAXANTHIN; LUTEIN
AB Plant breeding has developed corn genotypes with grain higher in levels of carotenoids. Dietary consumption of specific carotenoids by humans has been associated with improved eye health, notably with some protection against age-related macular degeneration. Increasing dietary sources of macular carotenoids in the standard American diet might be accomplished by using high carotenoid Orange Corn in poultry diets to increase macular carotenoid concentrations in egg yolks. Three hundred sixty laying hens (Novogen White) were fed three different diets over 31 days. Each diet had six replicates of 20 hens housed in enrichable colony cages. The only difference was the type of corn included - white, yellow, and orange, in order to assess the impact of each type of corn on egg production, yolk pigmentation, and carotenoid deposition. This study assessed yolk color and carotenoid densities using a portable colorimeter and the DSM YolkFan, and by high performance liquid chromatography (HPLC) on eggs from the feeding study and on 43 cartons of 12 eggs commercially available and produced in various production settings: conventional cage, cage-free, cage-free organic, free-range/pasture, and free-range/pasture organic. Yolks from hens fed with the Orange Corn diet produced eggs with higher (P < 0.01) DSM yolk color (6 to 10) and total xanthophylls (23.5 to 35.3 mu g/g of egg yolk) compared to the yellow diet (5 to 6 DSM and 12.3 to 17.7 mu g/g xanthophylls) and white diet (1 to 2 DSM and 2.5 to 3.0 mu g/g xanthophylls). Egg yolks reached a maximum xanthophyll accumulation with the Orange Corn diet (35.3 mu g/g of egg yolk) after twelve days of treatment and maintained steady levels at subsequent time points. In general, xanthophyll levels in yolks from the Orange Corn diet were superior (30-61% higher) to any of the commercial egg brands, suggesting that feeding high carotenoid Orange Corn increases xanthophyll density in eggs.
C1 [Ortiz, Darwin; Rocheford, Torbert] Purdue Univ, Dept Agron, W Lafayette, IN 47907 USA.
   [Jarrett, Rachel; Ring, Ashley; Scoles, Kailynn L.; Karcher, Darrin M.] Purdue Univ, Dept Anim Sci, W Lafayette, IN 47907 USA.
   [Lawson, Tyler; Hoverman, Lisa; Rocheford, Evan] NutraMaize, W Lafayette, IN USA.
C3 Purdue University System; Purdue University; Purdue University West
   Lafayette Campus; Purdue University System; Purdue University; Purdue
   University West Lafayette Campus
RP Ortiz, D (通讯作者)，Purdue Univ, Dept Agron, W Lafayette, IN 47907 USA.
EM dortizos@purdue.edu
RI Ortiz, Darwin/B-5659-2018
OI Ortiz, Darwin/0000-0003-4321-1273
FU USDA SBIR grant [2017-33610-26980]; Patterson Chair funds; USDA National
   Institute of Food and Agriculture, Hatch project [1024772]
FX Special thanks to Jason Fields and his staff at the Purdue University
   ASREC Poultry Unit for day-to-day daily assistance at the farm, and
   Marsha Kern for assistance in producing and handling the corn for the
   diets. This project was supported by a USDA SBIR grant awarded to
   NutraMaize (Award Number 2017-33610-26980) with a subaward to Purdue,
   Patterson Chair funds, and the USDA National Institute of Food and
   Agriculture, Hatch project 1024772. Any opinions, findings, and
   conclusions or recommendations expressed in this material are those of
   the authors and do not necessarily reflect the views of the funding
   organizations.
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NR 47
TC 6
Z9 6
U1 1
U2 10
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
EI 1525-3171
J9 POULTRY SCI
JI Poult. Sci.
PD JUL
PY 2021
VL 100
IS 7
AR 101117
DI 10.1016/j.psj.2021.101117
PG 9
WC Agriculture, Dairy & Animal Science
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Agriculture
GA TB9EF
UT WOS:000668246700017
PM 34102484
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Feng, L
   Cao, LN
   Zhang, Y
   Wang, F
AF Feng, Le
   Cao, Lining
   Zhang, Yao
   Wang, Fang
TI Detecting A beta Deposition and RPE Cell Senescence in the Retinas of
   SAMP8 Mice
SO DISCOVERY MEDICINE
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; AMYLOID-BETA; FUNDUS AUTOFLUORESCENCE; MACULAR
   DEGENERATION; IN-VIVO; INFLAMMATORY NETWORKS; SECRETORY PHENOTYPE;
   GEOGRAPHIC ATROPHY; DRUSEN; STIMULATION
AB Aim: Our previous study indicated that A beta-induced Retinal Pigment Epithelial (RPE) cell senescence may be associated with chronic inflammation in age-related macular degeneration (AMD). The present study was designed to explore whether A beta deposition and RPE senescence could be found in the senescence-prone mouse strain 8 (SAMP8), which is an animal model for AMD. Methods: Eyes of both SAMP8 and age-matched SAMR1 (SAM resistant) mice were examined in vivo by fundus photography and electroretinography (ERG). Retinal morphological features were assessed using light and electron microscopy. A beta deposition and p16-positive senescent RPE cells were traced using immunofluorescence labeling. P16 expression was detected using western blot. Expressions of IL-6 and IL-8 in RPE/choroid were analyzed using RT-PCR. Results: In fundus of SAMP8, age-dependent increase of drusen-like lesions and the increase of granular autofluorescent spots were respectively detected using IR (near-infrared) and AF (autofluorescence) imaging of confocal scanning laser ophthalmoscope. The amplitude of the ERGs declined with age in SAMP8 and these changes were paralleled with the significant changes in retinal morphological features examined by funduscopy. Histopathological analysis found significant loss of photoreceptor outer segments (OS) and abnormal localization of RPE cells in aged SAMP8 mice. Degenerative changes in RPE cells of aged SAMP8 mice, including massive vacuoles, thickened Bruch's membrane (BrM), and loss of basal infoldings were further confirmed by electron microscopy. Increased A beta deposits in OS layer and p16-positive senescent RPE cells were observed using immunofluorescence microscopy. Western blot confirmed that P16 expression was significantly increased in RPE cells of aged SAMP8 mice. Proinflammatory IL-6 and IL-8 expressions were significantly upregulated in RPE/choroid of aged SAMP8 mice. Conclusions: Our results showed that aged SAMP8 mice developed ocular pathology similar to some features of human AMD. In this AMD mouse model, A beta deposition and RPE senescence may be associated with AMD development, and RPE senescence is likely a mechanistic link between A beta deposition and inflammation.
C1 [Feng, Le; Cao, Lining; Zhang, Yao; Wang, Fang] Tongji Univ, Shanghai Peoples Hosp, Dept Ophthalmol, Shanghai 200072, Peoples R China.
C3 Tongji University
RP Wang, F (通讯作者)，Tongji Univ, Shanghai Peoples Hosp, Dept Ophthalmol, Shanghai 200072, Peoples R China.
EM 1433762@tongji.edu.cn
FU Outstanding Youths Program of Shanghai Tongji University [1501219059];
   Specialized Research Fund for the Doctoral Program of Higher Education
   [20130072120054]; National Natural Science Foundation of China
   [81400417]
FX We thank the Biochemistry and Molecular Biology Institute of Shanghai
   Tenth People's Hospital for their technological support. This work was
   supported by Outstanding Youths Program of Shanghai Tongji University
   (1501219059), Specialized Research Fund for the Doctoral Program of
   Higher Education (20130072120054), and the National Natural Science
   Foundation of China (81400417).
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NR 44
TC 14
Z9 15
U1 0
U2 4
PU DISCOVERY MEDICINE
PI TIMONIUM
PA 10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA
SN 1539-6509
EI 1944-7930
J9 DISCOV MED
JI Discov. Med.
PD MAR
PY 2016
VL 21
IS 115
BP 149
EP 158
PG 10
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA DM5QX
UT WOS:000376406200001
PM 27115165
DA 2022-11-30
ER

PT J
AU Chen, Q
   Niu, SJ
   Shen, HL
   Leng, T
   de Sisternes, L
   Rubin, DL
AF Chen, Qiang
   Niu, Sijie
   Shen, Honglie
   Leng, Theodore
   de Sisternes, Luis
   Rubin, Daniel L.
TI Restricted Summed-Area Projection for Geographic Atrophy Visualization
   in SD-OCT Images
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE geographic atrophy visualization; spectral domain optical coherence
   tomography; restricted summed-area projection; choroidal vasculature;
   geographic separability
ID OPTICAL COHERENCE TOMOGRAPHY; FUNDUS AUTOFLUORESCENCE; DRUSEN;
   CLASSIFICATION; PROGRESSION; RPE
AB Purpose: To enhance the rapid assessment of geographic atrophy (GA) across the macula in a single projection image generated from three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) scans by introducing a novel restricted summed-area projection (RSAP) technique.
   Methods: We describe a novel en face GA visualization technique, the RSAP, by restricting the axial projection of SD-OCT images to the regions beneath the Bruch's membrane (BM) boundary and also considering the choroidal vasculature's influence on GA visualization. The technique analyzes the intensity distribution beneath the retinal pigment epithelium (RPE) layer to fit a cross-sectional surface in the sub-RPE region. The area is taken as the primary GA projection. A median filter is then adopted to smooth the generated GA projection image. The RSAP technique was evaluated in 99 3D SD-OCT data sets from 27 eyes of 21 patients presenting with advanced nonexudative age-related macular degeneration and GA. We used the mean difference between GA and background regions and GA separability metric to measure GA contrast and distinction in the generated images, respectively. We compared our results with two existing GA projection techniques, the summed-voxel projection (SVP) and Sub-RPE Slab techniques.
   Results: Comparative results demonstrate that the RSAP technique is more effective in displaying GA than the SVP and Sub-RPE Slab. The average of the mean difference between GA and background regions and the GA separability based on SVP, Sub-RPE Slab, and RSAP were 0.129/0.880, 0.238/0.919, and 0.276/0.938, respectively.
   Conclusions: The RSAP technique was more effective for GA visualization than the conventional SVP and Sub-RPE Slab techniques. Our technique decreases choroidal vasculature influence on GA projection images by analyzing the intensity distribution characteristics in sub-RPE regions. The generated GA projection image with the RSAP technique has improved contrast and distinction.
   Translational Relevance: Our method for automated generation of GA projection images from SD-OCT images may improve the visualization of the macular abnormalities and the management of GA.
C1 [Chen, Qiang; Niu, Sijie; Shen, Honglie] Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, 200 Xiao Ling Wei, Nanjing 210094, Jiangsu, Peoples R China.
   [de Sisternes, Luis; Rubin, Daniel L.] Stanford Univ, Sch Med, Biomed Informat Res, Dept Radiol & Med, Stanford, CA 94305 USA.
   [Leng, Theodore] Stanford Univ, Sch Med, Byers Eye Inst Stanford, Palo Alto, CA 94304 USA.
C3 Nanjing University of Science & Technology; Stanford University;
   Stanford University
RP Chen, Q (通讯作者)，Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, 200 Xiao Ling Wei, Nanjing 210094, Jiangsu, Peoples R China.
EM chen2qiang@njust.edu.cn
RI chen, qiang/GWZ-7308-2022; Leng, Theodore/AAQ-7459-2020
FU Fundamental Research Funds for the Central Universities
   [30920140111004]; Jiangsu Province [2014-SWYY-024]; Qing Lan Project;
   Bio-X Interdisciplinary Initiatives Program of Stanford University;
   Spectrum-SPADA innovation grant from Stanford University
   (NIH-NCATS-CTSA-SPECTRUM)
FX Supported by a grant from the Fundamental Research Funds for the Central
   Universities (30920140111004), a six talent peaks project in Jiangsu
   Province (2014-SWYY-024), the Qing Lan Project, the Bio-X
   Interdisciplinary Initiatives Program of Stanford University, and a
   Spectrum-SPADA innovation grant from Stanford University
   (NIH-NCATS-CTSA-SPECTRUM).
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NR 30
TC 15
Z9 16
U1 1
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD SEP
PY 2015
VL 4
IS 5
AR 2
DI 10.1167/tvst.4.5.2
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ED2GJ
UT WOS:000388661700002
PM 26347016
OA Green Published
DA 2022-11-30
ER

PT J
AU Chang, Q
   Berdyshev, E
   Cao, DC
   Bogaard, JD
   White, JJ
   Chen, SQ
   Shah, R
   Mu, WB
   Grantner, R
   Bettis, S
   Grassi, MA
AF Chang, Qing
   Berdyshev, Evgeny
   Cao, Dingcai
   Bogaard, Joseph D.
   White, Jerry J.
   Chen, Siquan
   Shah, Ravi
   Mu, Wenbo
   Grantner, Rita
   Bettis, Sam
   Grassi, Michael A.
TI Cytochrome P450 2C Epoxygenases Mediate Photochemical Stress-induced
   Death of Photoreceptors
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Apoptosis; Calcium; Cytochrome P450; Drug Screening; Eicosanoid; Fatty
   Acid; Necrosis (Necrotic Death)
ID INDUCED RETINAL DEGENERATION; MACULAR DEGENERATION;
   RETINITIS-PIGMENTOSA; ARACHIDONIC-ACID; LIGHT DAMAGE; CELL-DEATH;
   DOCOSAHEXAENOIC ACID; ROD PHOTORECEPTORS; RAT RETINA; VISUAL IMPAIRMENT
AB Background: New pharmacological entities are actively sought for treatment of inherited and age-related retinal degenerative diseases. Results: Sulfaphenazole, a selective inhibitor of human cytochrome P450 (CYP) 2C9 enzyme, was identified as a novel cytoprotective agent against light-induced death of photoreceptors. Conclusion: Cytochrome P450 CYP2C epoxygenases mediate photochemical stress-induced death of photoreceptors. Significance: The CYP monooxygenase system is a risk factor for retinal photodamage.
   Degenerative loss of photoreceptors occurs in inherited and age-related retinal degenerative diseases. A chemical screen facilitates development of new testing routes for neuroprotection and mechanistic investigation. Herein, we conducted a mouse-derived photoreceptor (661W cell)-based high throughput screen of the Food and Drug Administration-approved Prestwick drug library to identify putative cytoprotective compounds against light-induced, synthetic visual chromophore-precipitated cell death. Different classes of hit compounds were identified, some of which target known genes or pathways pathologically associated with retinitis pigmentosa. Sulfaphenazole (SFZ), a selective inhibitor of human cytochrome P450 (CYP) 2C9 isozyme, was identified as a novel and leading cytoprotective compound. Expression of CYP2C proteins was induced by light. Gene-targeted knockdown of CYP2C55, the homologous gene of CYP2C9, demonstrated viability rescue to light-induced cell death, whereas stable expression of functional CYP2C9-GFP fusion protein further exacerbated light-induced cell death. Mechanistically, SFZ inhibited light-induced necrosis and mitochondrial stress-initiated apoptosis. Light elicited calcium influx, which was mitigated by SFZ. Light provoked the release of arachidonic acid from membrane phospholipids and production of non-epoxyeicosatrienoic acid metabolites. Administration of SFZ further stimulated the production of non-epoxyeicosatrienoic acid metabolites, suggesting a metabolic shift of arachidonic acid under inhibition of the CYP2C pathway. Together, our findings indicate that CYP2C genes play a direct causative role in photochemical stress-induced death of photoreceptors and suggest that the CYP monooxygenase system is a risk factor for retinal photodamage, especially in individuals with Stargardt disease and age-related macular degeneration that deposit condensation products of retinoids.
C1 [Chang, Qing; Cao, Dingcai; Bogaard, Joseph D.; Shah, Ravi; Mu, Wenbo; Grassi, Michael A.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA.
   [White, Jerry J.] Univ Illinois, Res Resources Ctr, Chicago, IL 60612 USA.
   [Berdyshev, Evgeny] Univ Illinois, Sect Pulm Crit Care Sleep & Allergy, Chicago, IL 60612 USA.
   [Chen, Siquan; Grantner, Rita; Bettis, Sam] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
C3 University of Illinois System; University of Illinois Chicago;
   University of Illinois Chicago Hospital; University of Illinois System;
   University of Illinois Chicago; University of Illinois Chicago Hospital;
   University of Illinois System; University of Illinois Chicago;
   University of Illinois Chicago Hospital; University of Chicago
RP Chang, Q (通讯作者)，Univ Illinois, Dept Ophthalmol & Visual Sci, 1905 West Taylor St, Chicago, IL 60612 USA.
EM changq@uic.edu; grassim@uic.edu
FU National Institutes of Health, NEI [EY001792]; Hope for Vision;
   Foundation Fighting Blindness; Parent Petroleum; Research to Prevent
   Blindness; NATIONAL EYE INSTITUTE [P30EY001792] Funding Source: NIH
   RePORTER
FX This work was supported, in whole or in part, by National Institutes of
   Health Grant EY001792, an NEI core grant. This work was also supported
   by funding from Hope for Vision, Foundation Fighting Blindness, Parent
   Petroleum, and Research to Prevent Blindness.
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NR 90
TC 13
Z9 13
U1 0
U2 15
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 21
PY 2014
VL 289
IS 12
BP 8337
EP 8352
DI 10.1074/jbc.M113.507152
PG 16
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA AD3PG
UT WOS:000333157500027
PM 24519941
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Anderson, OA
   Finkelstein, A
   Shima, DT
AF Anderson, Owen A.
   Finkelstein, Arthur
   Shima, David T.
TI A2E Induces IL-1 beta Production in Retinal Pigment Epithelial Cells via
   the NLRP3 Inflammasome
SO PLOS ONE
LA English
DT Article
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; LIPOFUSCIN FLUOROPHORE;
   NALP3 INFLAMMASOME; BRUCHS MEMBRANE; HUMAN RPE; CHOROIDAL
   NEOVASCULARIZATION; PHOTOOXIDATION PRODUCTS; COMPLEMENT ACTIVATION;
   ALZHEIMERS-DISEASE
AB Aims: With ageing extracellular material is deposited in Bruch's membrane, as drusen. Lipofuscin is deposited in retinal pigment epithelial cells. Both of these changes are associated with age related macular degeneration, a disease now believed to involve chronic inflammation at the retinal-choroidal interface. We hypothesise that these molecules may act as danger signals, causing the production of inflammatory chemokines and cytokines by the retinal pigment epithelium, via activation of pattern recognition receptors.
   Methods: ARPE-19 cells were stimulated in vitro with the following reported components of drusen: amyloid-beta (1-42), Carboxyethylpyrrole (CEP) modified proteins (CEP-HSA), N epsilon-(Carboxymethyl)lysine (CML) modified proteins and aggregated vitronectin. The cells were also stimulated with the major fluorophore of lipofuscin: N-retinylidene-N-retinylethanolamine (A2E). Inflammatory chemokine and cytokine production was assessed using Multiplex assays and ELISA. The mechanistic evaluation of the NLRP3 inflammasome pathway was assessed in a stepwise fashion.
   Results: Of all the molecules tested only A2E induced inflammatory chemokine and cytokine production. 25 mu M A2E induced the production of significantly increased levels of the chemokines IL-8, MCP-1, MCG and MIP-1 alpha, the cytokines IL-1 beta, IL-2, IL-6, and TNF-alpha, and the protein VEGF-A. The release of IL-1 beta was studied further, and was determined to be due to NLRP3 inflammasome activation. The pathway of activation involved endocytosis of A2E, and the three inflammasome components NLRP3, ASC and activated caspase-1. Immunohistochemical staining of ABCA4 knockout mice, which show progressive accumulation of A2E levels with age, showed increased amounts of IL-1 beta proximal to the retinal pigment epithelium.
   Conclusions: A2E has the ability to stimulate inflammatory chemokine and cytokine production by RPE cells. The pattern recognition receptor NLRP3 is involved in this process. This provides further evidence for the link between A2E, inflammation, and the pathogenesis of AMD. It also supports the recent discovery of NLRP3 inflammasome activation in AMD.
C1 [Anderson, Owen A.; Finkelstein, Arthur; Shima, David T.] UCL Inst Ophthalmol Ocular Biol & Therapeut, London, England.
C3 University of London; University College London
RP Shima, DT (通讯作者)，UCL Inst Ophthalmol Ocular Biol & Therapeut, London, England.
EM d.shima@ucl.ac.uk
FU Department of Health; UCL Institute of Ophthalmology for a Biomedical
   Research Centre for Ophthalmology; MRC [G0800946] Funding Source: UKRI;
   Medical Research Council [G0800946] Funding Source: researchfish
FX The authors acknowledge (a proportion of their) financial support from
   the Department of Health through the award made by the National
   Institute for Health Research to Moorfields Eye Hospital NHS Foundation
   Trust and UCL Institute of Ophthalmology for a Biomedical Research
   Centre for Ophthalmology. The views expressed in this publication are
   those of the authors and not necessarily those of the Department of
   Health (http://www.nihr.ac.uk/Pages/default.aspx). The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.
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NR 68
TC 109
Z9 110
U1 0
U2 17
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 28
PY 2013
VL 8
IS 6
AR e67263
DI 10.1371/journal.pone.0067263
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 174IH
UT WOS:000321148400050
PM 23840644
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Friberg, TR
   Bilonick, RA
   Brennen, P
AF Friberg, Thomas R.
   Bilonick, Richard A.
   Brennen, Peter
TI Is Drusen Area Really So Important? An Assessment of Risk of Conversion
   to Neovascular AMD Based on Computerized Measurements of Drusen
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID FACTOR-H POLYMORPHISM; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION;
   PROGNOSIS; EYES
AB PURPOSE. To assess the relative risk of an eye's conversion to wet age-related macular degeneration (AMD) based primarily on drusen measurements obtained from analysis of digitized images.
   METHODS. Four hundred forty-four subjects (820 eyes) enrolled in the Age-Related Eye Disease Study (AREDS I) and 78 subjects (129 eyes) from the Prophylactic Treatment of AMD trial (PTAMD) were studied retrospectively. Drusen size, distribution, drusen area, and hyperpigmentation in two central macular regions on baseline fundus images were determined using an image analysis algorithm. The relative risk for choroidal neovascularization (CNV) based on drusen area, presence of one or five large drusen, hyperpigmentation, and fellow eye status was calculated.
   RESULTS. Odds ratios (ORs) for measured drusen area within the 1000- and 3000-mu m regions were 1.644* (1.251-2.162) and 1.278 (0.927-1.762) for AREDS eyes and 0.832 (0.345-2.005) and 1.094 (0.524-2.283) for PTAMD eyes (*P < 0.05). In the 1000-mu m region, respective ORs for the presence of a large druse, hyperpigmentation, and fellow eye affected were 2.60, 1.71, and 6.44* for AREDS eyes and 8.24, 1.37, and 17.56* for PTAMD eyes; for the 3000-mu m region, ORs were 3.45*, 3.40*, and 4.59* for AREDS and nonsignificant, 6.58, and 11.62* for PTAMD eyes, respectively.
   CONCLUSIONS. Total drusen area, presence of large drusen, and the presence of hyperpigmentation were not consistent risk factors for an eye's development of CNV. Risk depended on study cohort as well as location. Having an affected fellow eye was the strongest and most consistent risk factor across all models. A larger drusen area does not necessarily increase an eye's risk of conversion to CNV. (Invest Ophthalmol Vis Sci. 2012;53:1742-1751) DOI:10.1167/iovs.11-9338
C1 [Friberg, Thomas R.] Univ Pittsburgh, UPMC Eye Ctr, Dept Ophthalmol & Bioengn, Pittsburgh, PA 15213 USA.
   [Friberg, Thomas R.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15213 USA.
   [Bilonick, Richard A.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15213 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; Pennsylvania Commonwealth System of Higher Education
   (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of
   Higher Education (PCSHE); University of Pittsburgh
RP Friberg, TR (通讯作者)，Univ Pittsburgh, UPMC Eye Ctr, Dept Ophthalmol & Bioengn, 203 Lothrop St,Suite 824, Pittsburgh, PA 15213 USA.
EM friberg@pitt.edu
FU Eye and Ear Foundation of Pittsburgh, Pennsylvania; Research to Prevent
   Blindness; National Institutes of Health [P30 EY008098]; NATIONAL EYE
   INSTITUTE [P30EY008098] Funding Source: NIH RePORTER
FX Supported by The Eye and Ear Foundation of Pittsburgh, Pennsylvania; an
   unrestricted grant from the Research to Prevent Blindness; and National
   Institutes of Health CORE grant P30 EY008098.
CR Ambati J, 2003, SURV OPHTHALMOL, V48, P257, DOI 10.1016/S0039-6257(03)00030-4
   Au Eong KG, 2002, AGE RELATED MACULAR, P389
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NR 25
TC 13
Z9 13
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2012
VL 53
IS 4
BP 1742
EP 1751
DI 10.1167/iovs.11-9338
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 937PC
UT WOS:000303669400006
PM 22395875
OA Green Published
DA 2022-11-30
ER

PT J
AU Vogt, SD
   Curcio, CA
   Wang, L
   Li, CM
   McGwin, G
   Medeiros, NE
   Philp, NJ
   Kimble, JA
   Read, RW
AF Vogt, Susan D.
   Curcio, Christine A.
   Wang, Lan
   Li, Chuan-Ming
   McGwin, Gerald, Jr.
   Medeiros, Nancy E.
   Philp, Nancy J.
   Kimble, James A.
   Read, Russell W.
TI Retinal pigment epithelial expression of complement regulator CD46 is
   altered early in the course of geographic atrophy
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; geographic atrophy; complement; CD46;
   inflammation; immunohistochemistry; histopathology; human
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; BRUCHS-MEMBRANE;
   CHORIORETINAL ATROPHY; COMPONENT 2; DRUSEN; RPE; FEATURES; PROTEIN;
   MODULATION
AB In geographic atrophy (GA), the non-neovascular end stage of age-related macular degeneration (AMD), the macular retinal pigment epithelium (RPE) progressively degenerates. Membrane cofactor protein (MCP. CD46) is the only membrane-bound regulator of complement expressed on the human RPE basolateral surface. Based on evidence of the role of complement in AMD, we hypothesized that altered CD46 expression on the RPE would be associated with GA development and/or progression. Here we report the timeline of CD46 protein expression changes across the GA transition zone, relative to control eyes, and relative to events in other chorioretinal layers. Eleven donor eyes (mean age 87.0 +/- 4.1 yr) with GA and 5 control eyes (mean age 84.0 +/- 8.9 yr) without GA were evaluated. Macular cryosections were stained with PASH for basal deposits, von Kossa for calcium, and for CD46 immunoreactivity. Internal controls for protein expression were provided by an independent basolateral protein, monocarboxylate transporter 3 (MCT3) and an apical protein, ezrin. Within zones defined by 8 different semi-quantitative grades of RPE morphology, we determined the location and intensity of immunoreactivity, outer segment length, and Bruch's membrane calcification. Differences between GA and control eyes and between milder and more severe RPE stages in GA eyes were assessed statistically. Increasing grades of RPE degeneration were associated with progressive loss of polarity and loss of intensity of staining of CD46, beginning with the stages that are considered normal aging (grades 0-1). Those GA stages with affected CD46 immunoreactivity exhibited basal laminar deposit, still-normal photoreceptors, and concomitant changes in control protein expression. Activated or anteriorly migrated RPE (grades 2-3) exhibited greatly diminished CD46. Changes in RPE CD46 expression thus occur early in GA, before there is evidence of morphological RPE change. At later stages of degeneration, CD46 alterations occur within a context of altered RPE polarity. These changes precede degeneration of the overlying retina and suggest that therapeutic interventions be targeted to the RPE. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Vogt, Susan D.; Curcio, Christine A.; Wang, Lan; Li, Chuan-Ming; McGwin, Gerald, Jr.; Kimble, James A.; Read, Russell W.] Univ Alabama Birmingham, Sch Med, Dept Ophthalmol, Birmingham, AL 35233 USA.
   [McGwin, Gerald, Jr.] Univ Alabama Birmingham, Sch Med, Dept Surg, Birmingham, AL 35233 USA.
   [Read, Russell W.] Univ Alabama Birmingham, Sch Med, Dept Pathol, Birmingham, AL 35233 USA.
   [McGwin, Gerald, Jr.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA.
   [Medeiros, Nancy E.] Retina Specialists N Alabama, Huntsville, AL USA.
   [Philp, Nancy J.] Thomas Jefferson Univ, Dept Pathol, Philadelphia, PA 19107 USA.
   [Kimble, James A.] Retina Specialists Alabama, Birmingham, AL USA.
C3 University of Alabama System; University of Alabama Birmingham;
   University of Alabama System; University of Alabama Birmingham;
   University of Alabama System; University of Alabama Birmingham;
   University of Alabama System; University of Alabama Birmingham;
   Jefferson University
RP Read, RW (通讯作者)，Univ Alabama Birmingham, Sch Med, Dept Ophthalmol, 700 S 18th St,Suite 601, Birmingham, AL 35233 USA.
EM rwr@uab.edu
OI Philp, Nancy/0000-0001-7028-0448
FU International Retinal Research Foundation; EyeSight Foundation of
   Alabama [FY2006-07-31]; NIH [EY06109, EY012042]; Prevent Blindness,
   Inc.; NATIONAL EYE INSTITUTE [R01EY006109, R56EY012042, R01EY012042]
   Funding Source: NIH RePORTER
FX Support: International Retinal Research Foundation (no grant #) (SDV,
   CAC, RWR); EyeSight Foundation of Alabama grant FY2006-07-31 (SDV, RWR);
   NIH grant EY06109 (CAC); NIH grant EY012042 (NJP); and unrestricted
   funds to the Department of Ophthalmology from Research to Prevent
   Blindness, Inc., and EyeSight Foundation of Alabama. Dr. Read is a
   Research to Prevent Blindness Physician-Scientist.
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NR 79
TC 79
Z9 80
U1 0
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD OCT
PY 2011
VL 93
IS 4
BP 413
EP 423
DI 10.1016/j.exer.2011.06.002
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 853TZ
UT WOS:000297449900012
PM 21684273
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Benny, O
   Nakai, K
   Yoshimura, T
   Bazinet, L
   Akula, JD
   Nakao, S
   Hafezi-Moghadam, A
   Panigrahy, D
   Pakneshan, P
   D'Amato, RJ
AF Benny, Ofra
   Nakai, Kei
   Yoshimura, Takeru
   Bazinet, Lauren
   Akula, James D.
   Nakao, Shintaro
   Hafezi-Moghadam, Ali
   Panigrahy, Dipak
   Pakneshan, Pouya
   D'Amato, Robert J.
TI Broad Spectrum Antiangiogenic Treatment for Ocular Neovascular Diseases
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; CYTOKINE EXPRESSION;
   ACTIVATION STEPS; PHOTOTRANSDUCTION; ANGIOGENESIS; RANIBIZUMAB;
   RETINOPATHY; RPE; ROD
AB Pathological neovascularization is a hallmark of late stage neovascular (wet) age-related macular degeneration (AMD) and the leading cause of blindness in people over the age of 50 in the western world. The treatments focus on suppression of choroidal neovascularization (CNV), while current approved therapies are limited to inhibiting vascular endothelial growth factor (VEGF) exclusively. However, this treatment does not address the underlying cause of AMD, and the loss of VEGF's neuroprotective can be a potential side effect. Therapy which targets the key processes in AMD, the pathological neovascularization, vessel leakage and inflammation could bring a major shift in the approach to disease treatment and prevention. In this study we have demonstrated the efficacy of such broad spectrum antiangiogenic therapy on mouse model of AMD. Methods and Findings: Lodamin, a polymeric formulation of TNP-470, is a potent broad-spectrum antiangiogenic drug. Lodamin significantly reduced key processes involved in AMD progression as demonstrated in mice and rats. Its suppressive effects on angiogenesis, vascular leakage and inflammation were studied in a wide array of assays including; a Matrigel, delayed-type hypersensitivity (DTH), Miles assay, laser-induced CNV and corneal micropocket assay. Lodamin significantly suppressed the secretion of various pro-inflammatory cytokines in the CNV lesion including monocyte chemotactic protein-1 (MCP-1/Ccl2). Importantly, Lodamin was found to regress established CNV lesions, unlike soluble fms-like tyrosine kinase-1 (sFlk-1). The drug was found to be safe in mice and have little toxicity as demonstrated by electroretinography (ERG) assessing retinal and by histology.
   Conclusions: Lodamin, a polymer formulation of TNP-470, was identified as a first in its class, broad-spectrum antiangiogenic drug that can be administered orally or locally to treat corneal and retinal neovascularization. Several unique properties make Lodamin especially beneficial for ophthalmic use. Our results support the concept that broad spectrum antiangiogenic drugs are promising agents for AMD treatment and prevention.
C1 [Benny, Ofra; Nakai, Kei; Yoshimura, Takeru; Bazinet, Lauren; Panigrahy, Dipak; Pakneshan, Pouya; D'Amato, Robert J.] Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program, Boston, MA 02115 USA.
   [Benny, Ofra; Nakai, Kei; Yoshimura, Takeru; Bazinet, Lauren; Panigrahy, Dipak; Pakneshan, Pouya; D'Amato, Robert J.] Harvard Univ, Sch Med, Dept Surg, Childrens Hosp Boston, Boston, MA 02115 USA.
   [Benny, Ofra; Nakai, Kei; Yoshimura, Takeru; Bazinet, Lauren; Akula, James D.; Pakneshan, Pouya; D'Amato, Robert J.] Harvard Univ, Sch Med, Dept Ophthalmol, Childrens Hosp Boston, Boston, MA USA.
   [Nakao, Shintaro; Hafezi-Moghadam, Ali] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
C3 Harvard University; Boston Children's Hospital; Harvard Medical School;
   Harvard University; Boston Children's Hospital; Harvard Medical School;
   Harvard University; Boston Children's Hospital; Harvard Medical School;
   Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary
RP Benny, O (通讯作者)，Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program, Boston, MA 02115 USA.
EM ofra.bennyratsaby@childrens.harvard.edu
RI Benny, Ofra/AAB-3294-2021
OI Akula, James/0000-0001-8049-1812; Yoshimura, Takeru/0000-0002-5983-7193;
   Hafezi-Moghadam, Ali/0000-0002-5336-0697
FU Departmental support fund
FX Departmental support fund. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 32
TC 22
Z9 23
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 1
PY 2010
VL 5
IS 9
AR e12515
DI 10.1371/journal.pone.0012515
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 645KT
UT WOS:000281456100016
PM 20824139
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Alster, Y
   Bressler, NM
   Bressler, SB
   Brimacombe, JA
   Crompton, RM
   Duh, YJ
   Gabel, VP
   Heier, JS
   Ip, MS
   Loewenstein, A
   Packo, KH
   Stur, M
   Toaff, T
AF Alster, Y
   Bressler, NM
   Bressler, SB
   Brimacombe, JA
   Crompton, RM
   Duh, YJ
   Gabel, VP
   Heier, JS
   Ip, MS
   Loewenstein, A
   Packo, KH
   Stur, M
   Toaff, T
CA Preferential Hyperacuity Perimetry
TI Preferential hyperacuity perimeter (PreView PHP) for detecting choroidal
   neovascularization study
SO OPHTHALMOLOGY
LA English
DT Article
AB Purpose: To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD.
   Design: Prospective, comparative, concurrent, nonrandomized, multicenter study. Participants: Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD.
   Methods: After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD.
   Main Outcome Measures: A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%.
   Results: Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% Cl, 76%-95%).
   Conclusions: Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the intermediate stage of AMD.
C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol,Retina Div, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Bressler, NM (通讯作者)，5160 Hacienda Dr, Dublin, CA 94568 USA.
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   [No title captured]
NR 22
TC 68
Z9 71
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD OCT
PY 2005
VL 112
IS 10
BP 1758
EP 1765
DI 10.1016/j.ophtha.2005.06.008
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 970IS
UT WOS:000232299200016
PM 16154198
DA 2022-11-30
ER

PT J
AU Kaczynski, TJ
   Au, ED
   Farkas, MH
AF Kaczynski, Tadeusz J.
   Au, Elizabeth D.
   Farkas, Michael H.
TI Oxidative stress alters transcript localization of disease-associated
   genes in the retinal pigment epithelium
SO MOLECULAR VISION
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; NUCLEAR RETENTION; MESSENGER-RNA;
   STEM-CELLS; EXPRESSION; AUTOPHAGY; HIKESHI; RPE
AB Purpose: Nuclear retention is a mechanism whereby excess RNA transcripts are stored in the event that a cell needs to quickly respond to a stimulus; maintaining proper nuclear-to-cytoplasmic balance is important for cellular homeostasis and cell function. There are many mechanisms that are employed to determine whether to retain a transcript or export it to the cytoplasm, although the extent to which tissue or cell type, internal and external stressors, and disease pathogenesis affect this process is not yet clear. As the most biochemically active tissue in the body, the retina must mitigate endogenous and exogenous stressors to maintain cell health and tissue function. Oxidative stress, believed to contribute to the pathogenesis or progression of age-related macular degeneration (AMD) and inherited retinal dystrophies (IRDs), is produced both internally from biochemical processes as well as externally from environmental insult. Here, we evaluate the effect of oxidative stress on transcript localization in the retinal pigment epithelium (RPE), with specific focus on transcripts related to RPE function and disease.Methods: We performed poly(A) RNA sequencing on nuclear and cytoplasmic fractions from human induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) cells exposed to hydrogen peroxide (H2O2), as well as on untreated controls. Results: Under normal conditions, the number of mRNA transcripts retained in the nucleus exceeded that found in studies on other tissues. Further, the nuclear-to-cytoplasmic ratio of transcripts was altered following oxidative stress, as was the retention of genes associated with AMD and IRDs, as well as those that are important for RPE physiology.Conclusions: These results provide a localization catalog of all expressed mRNA in iPSC-RPE under normal conditions and after exposure to H2O2, shedding light on the extent to which H2O2 alters transcript localization and potentially offering insight into one mechanism through which oxidative stress may contribute to the progression of visual disorders.
C1 [Kaczynski, Tadeusz J.; Au, Elizabeth D.; Farkas, Michael H.] SUNY Buffalo, Dept Ophthalmol, Buffalo, NY USA.
   [Kaczynski, Tadeusz J.; Farkas, Michael H.] VA Med Ctr, Res Serv, Buffalo, NY USA.
   [Farkas, Michael H.] SUNY Buffalo, Dept Biochem, Buffalo, NY USA.
   [Farkas, Michael H.] VA Med Ctr Buffalo, 3495 Bailey Ave,Bldg 20,Rm 239, Buffalo, NY 14214 USA.
C3 State University of New York (SUNY) System; State University of New York
   (SUNY) Buffalo; State University of New York (SUNY) System; State
   University of New York (SUNY) Buffalo
RP Farkas, MH (通讯作者)，VA Med Ctr Buffalo, 3495 Bailey Ave,Bldg 20,Rm 239, Buffalo, NY 14214 USA.
EM mhfarkas@buffalo.edu
FU NIH/NEI [R01EY028553]; BrightFocus Foundation [M2019108]; VA Merit/BLRD
   Service [I01 BX004695]
FX This work was supported by grants R01EY028553 (NIH/NEI) , M2019108
   (BrightFocus Foundation) , I01 BX004695 (VA Merit/BLR & D Service) to
   MHF.
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NR 47
TC 0
Z9 0
U1 0
U2 0
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD OCT 2
PY 2022
VL 28
BP 340
EP 351
DI 10.1101/2021.01.07.425741
PG 12
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 5K4ZU
UT WOS:000869736800001
PM 36338668
DA 2022-11-30
ER

PT J
AU Liisborg, C
   Skov, V
   Kjaer, L
   Hasselbalch, HC
   Sorensen, TL
AF Liisborg, Charlotte
   Skov, Vibe
   Kjaer, Lasse
   Hasselbalch, Hans Carl
   Sorensen, Torben Lykke
TI Lower CXCR3 expression in both patients with neovascular AMD and
   advanced stages of chronic myeloproliferative blood cancers
SO PLOS ONE
LA English
DT Article
ID INDUCIBLE PROTEIN-10; MACULAR DEGENERATION; INHIBITION; CHEMOKINES;
   MONOCYTES; CELLS; IP-10; INFLAMMATION; ACTIVATION; LEUKOCYTES
AB Purpose
   Peripheral T cell CXCR3 expression has been found uniquely lower in patients having neovascular age-related macular degeneration (nAMD) than in healthy individuals. The CXCR3-axis has been shown to have angiostatic and antifibrotic properties. We have recently investigated systemic markers in patients with myeloproliferative neoplasms (MPNs) because of their higher prevalence of AMD, and we have observed higher systemic chronic low-grade inflammation and immunosenescence signs in MPNs with drusen (MPNd) compared to those with normal retinas (MPNn). The MPNs evolve in a biological continuum from early cancer-stages (essential thrombocytosis, polycythemia vera) to the advanced myelofibrosis stage. Especially myelofibrosis is characterized by bone marrow angiogenesis and fibrosis, similarly to retinal observations in nAMD. We speculate if we can find lower CXCR3 expression in MPNs, particularly myelofibrosis and if differences are seen between MPNd and MPNn. We also wanted to compare expression in nAMD and intermediate (i)AMD.
   Methods
   Patients in this cross-sectional study were 29 nAMD, 28 iAMD, 35 MPNd, and 27 MPNn. We performed flowcytometry on blood to measure CXCR3 expression.
   Results
   CD8+CXCR3 expression in nAMD was 6,1%, significantly lower than in iAMD 16%, MPNd 11%, MPNn 12% (p-values<0.05). Similar results were seen for CD4+CXCR3 expression. We also found CXCR3 expression decreasing over the MPN-continuum. For instance, in myelofibrosis, intermediate monocytes expression was 6.2%, significantly lower than 18% in ET and 18% in PV (p-values<0.05).
   Conclusions
   We find CXCR3 downregulation on T-cells and some monocyte subset in nAMD compared to iAMD, MPNd, and MPNn, in line with previous nAMD studies. We also find CXCR3 downregulation in most monocyte subsets over the MPN continuum. Systemic leukocyte CXCR3 expression could both be involved in changes seen in the retina and the bone marrow. Further understanding the CXCR3-axis in AMD and MPNs may elucidate underlying pathogenic mechanisms and reveal new targets for treatment.
C1 [Liisborg, Charlotte; Sorensen, Torben Lykke] Zealand Univ Hosp, Dept Ophthalmol, Roskilde, Denmark.
   [Liisborg, Charlotte; Hasselbalch, Hans Carl; Sorensen, Torben Lykke] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
   [Skov, Vibe; Kjaer, Lasse; Hasselbalch, Hans Carl] Zealand Univ Hosp, Dept Hematol, Roskilde, Denmark.
C3 University of Copenhagen
RP Liisborg, C (通讯作者)，Zealand Univ Hosp, Dept Ophthalmol, Roskilde, Denmark.; Liisborg, C (通讯作者)，Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
EM liisborg@c.dk
OI Liisborg, Charlotte/0000-0002-6353-6027
FU Fight for Sight, Denmark; Region Zealand's Research Promotion Fund,
   Denmark
FX The first author CL is a Ph.D. candidate at the University of Copenhagen
   (UCPH). The Ph.D. project was funded by "Fight for Sight, Denmark" and
   Region Zealand's Research Promotion Fund, Denmark. This work submitted
   is a partial requirement for a Ph.D. at UCPH. The sponsors are public
   and non-profit organizations. They had no role in the study's design and
   conduct; collection,
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NR 58
TC 1
Z9 1
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PY 2022
VL 17
IS 6
AR e0269960
DI 10.1371/journal.pone.0269960
PG 16
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 3Y3FU
UT WOS:000843613300101
PM 35709177
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Wu, J
   Gao, G
   Shi, FJ
   Xie, H
   Yang, Q
   Liu, DD
   Qu, SC
   Qin, HF
   Zhang, CY
   Xu, GT
   Liu, F
   Zhang, JF
AF Wu, Jing
   Gao, Ge
   Shi, Fanjun
   Xie, Hai
   Yang, Qian
   Liu, Dandan
   Qu, Sichang
   Qin, Haifeng
   Zhang, Chaoyang
   Xu, Guo-Tong
   Liu, Fang
   Zhang, Jingfa
TI Activated microglia-induced neuroinflammatory cytokines lead to
   photoreceptor apoptosis in A beta-injected mice
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE Age-related macular degeneration; Microglia; Photoreceptor;
   Neuroinflammatory cytokines
ID ALZHEIMERS-DISEASE; MACULAR DEGENERATION; MOUSE MODEL; PROTEIN
   AGGREGATION; RETINAL MICROGLIA; OXIDATIVE STRESS; INFLAMMATION;
   ACCUMULATION; DEPOSITION; IMPAIRMENT
AB Age-related macular degeneration (AMD) is mainly characterized by the progressive accumulation of drusen deposits and loss of photoreceptors and retinal pigment epithelial (RPE) cells. Because amyloid beta (A beta) is the main component of drusen, A beta-induced activated microglia most likely lead to neuroinflammation and play a critical role in the pathogenesis of AMD. However, the relationship between activated microglia-mediated neuroinflammatory cytokines and photoreceptor death has not been clarified. By subretinal injection of A beta(42) in mice, we mimicked an inflammatory milieu of AMD to better understand how activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in the AMD progression. We demonstrated that subretinal injection of A beta(42) induces microglial activation and increases inflammatory cytokine release, which gives rise to photoreceptor apoptosis in mice. Our results were verified in vitro by co-culture of A beta(42) activated primary microglia and the photoreceptor cell line 661W. We also demonstrated that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was involved in A beta(42)-induced microglial activation and inflammatory cytokine release. Overall, our findings indicate that activated microglia-derived neuroinflammatory cytokines could contribute to photoreceptor apoptosis under the stimulation of A beta(42). Moreover, this study may provide a potential therapeutic approach for AMD. Key messages
   Further explore the association between activated microglia-derived neuroinflammatory cytokine secretion and photoreceptor apoptosis under the stimulation of A beta 42. Subretinal injection of A beta 42 induces the activation of microglia and increases proinflammatory cytokines IL-1 beta and COX-2 expression in the retina, which could give rise to the deterioration of visual function and aggravate photoreceptor apoptosis in mice. Primary microglial are activated and the levels of proinflammatory cytokines are increased by A beta 42 stimulation which could increase the apoptosis of photoreceptor cell line 661W in vitro. The p38 MAPK signaling pathway is involved in microglial activation and photoreceptor apoptosis under A beta 42 treatment.
C1 [Wu, Jing; Qu, Sichang; Liu, Fang; Zhang, Jingfa] Tongji Univ, Shanghai Peoples Hosp 10, Dept Ophthalmol, Sch Med, Shanghai, Peoples R China.
   [Gao, Ge] Tongji Univ, Shanghai Peoples Hosp 10, Ctr Translat Neurodegenerat & Regenerat Therapy, Sch Med, Shanghai, Peoples R China.
   [Shi, Fanjun] Soochow Univ, Dept Ophthalmol, Affiliated Hosp 2, Suzhou, Peoples R China.
   [Xie, Hai; Yang, Qian; Liu, Dandan; Xu, Guo-Tong; Zhang, Jingfa] Tongji Univ, Dept Regenerat Med, Sch Med, Shanghai, Peoples R China.
   [Xie, Hai; Yang, Qian; Liu, Dandan; Xu, Guo-Tong; Zhang, Jingfa] Tongji Univ, Dept Pharmacol, Sch Med, Shanghai, Peoples R China.
   [Qin, Haifeng] Shanghai Changhai Hosp, Dept Ophthalmol, Shanghai, Peoples R China.
   [Zhang, Chaoyang; Zhang, Jingfa] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Ophthalmol, Shanghai Peoples Hosp 1, Shanghai, Peoples R China.
   [Zhang, Chaoyang; Zhang, Jingfa] Natl Clin Res Ctr Eye Dis, Shanghai, Peoples R China.
   [Zhang, Chaoyang; Zhang, Jingfa] Shanghai Key Lab Ocular Fundus Dis, Shanghai, Peoples R China.
   [Zhang, Chaoyang; Zhang, Jingfa] Shanghai Engn Ctr Precise Diag & Treatment Eye Di, Shanghai Engn Ctr Visual Sci & Photomed, Shanghai, Peoples R China.
C3 Tongji University; Tongji University; Soochow University - China; Tongji
   University; Tongji University; Naval Medical University; Shanghai Jiao
   Tong University
RP Liu, F; Zhang, JF (通讯作者)，Tongji Univ, Shanghai Peoples Hosp 10, Dept Ophthalmol, Sch Med, Shanghai, Peoples R China.; Zhang, JF (通讯作者)，Tongji Univ, Dept Regenerat Med, Sch Med, Shanghai, Peoples R China.; Zhang, JF (通讯作者)，Tongji Univ, Dept Pharmacol, Sch Med, Shanghai, Peoples R China.; Zhang, JF (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Ophthalmol, Shanghai Peoples Hosp 1, Shanghai, Peoples R China.; Zhang, JF (通讯作者)，Natl Clin Res Ctr Eye Dis, Shanghai, Peoples R China.; Zhang, JF (通讯作者)，Shanghai Key Lab Ocular Fundus Dis, Shanghai, Peoples R China.; Zhang, JF (通讯作者)，Shanghai Engn Ctr Precise Diag & Treatment Eye Di, Shanghai Engn Ctr Visual Sci & Photomed, Shanghai, Peoples R China.
EM fangliu_2004@yahoo.com; 13917311571@139.com
FU National Natural Science Foundation of China [81570852, 81870667,
   81970810, 81970811]; Science and Technology Commission of Shanghai
   Municipality [19495800700]; Clinical Research and Cultivation Project of
   Shanghai Municipal Hospital, China [SHDC12019X30]
FX This work was supported by the National Natural Science Foundation of
   China (81570852, 81870667, 81970810, 81970811), the Science and
   Technology Commission of Shanghai Municipality (19495800700), and the
   Clinical Research and Cultivation Project of Shanghai Municipal
   Hospital, China (SHDC12019X30).
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NR 65
TC 6
Z9 6
U1 6
U2 12
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0946-2716
EI 1432-1440
J9 J MOL MED
JI J. Mol. Med.
PD MAY
PY 2021
VL 99
IS 5
BP 713
EP 728
DI 10.1007/s00109-021-02046-6
EA FEB 2021
PG 16
WC Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Research & Experimental Medicine
GA RO7YT
UT WOS:000617113200002
PM 33575853
DA 2022-11-30
ER

PT J
AU Zhang, JH
   Zhou, HT
   Chen, JL
   Lv, XY
   Liu, HS
AF Zhang, Junhui
   Zhou, Haitao
   Chen, Juanli
   Lv, Xiaoyan
   Liu, Hongsong
TI Aloperine protects human retinal pigment epithelial cells against
   hydrogen peroxide-induced oxidative stress and apoptosis through
   activation of Nrf2/HO-1 pathway
SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
LA English
DT Article
DE Age-related macular degeneration (AMD); retinal pigment epithelium
   (RPE); oxidative stress; aloperine; Nrf2; HO-1 signaling pathway
AB Age-related macular degeneration (AMD) is a complex multifactorial disease associated with the dysfunction of retinal pigment epithelium (RPE). Aloperine is a quinolizidine alkaloid that has been proven to possess broad pharmacological activities. However, the effects of aloperine on AMD remain unclear. In the present study, we used hydrogen peroxide (H2O2) to induce oxidative injury in human RPE cells (ARPE-19 cells). ARPE-19 cells were pretreated with different concentrations of aloperine for 2 h, followed by H2O2 exposure. Cell cytotoxicity was determined using lactate dehydrogenase (LDH) release assay. Cell viability was measured using Cell Counting Kit-8 (CCK-8) assay. The reactive oxygen species (ROS) generation, malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-PX) activity were detected to reflect oxidative status. Western blot was performed to detect the expressions of bcl-2, bax, nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). The activity of caspase-3 was also assessed to indicate cell apoptosis. In addition, ARPE-19 cells were transfected with siNrf2 to knock down Nrf2. Our results showed that pretreatment with aloperine elevated the reduced cell viability of H2O2-induced ARPE-19 cells in a dose-dependent manner. Aloperine greatly decreased the production of ROS and MDA, and increased the activities of SOD and GSH-PX in H2O2-stimulated ARPE-19 cells. H2O2-caused a decrease in bcl-2 expression and increases in bax expression and caspase-3 activity were mitigated by aloperine. Moreover, aloperine treatment enhanced the expression levels of Nrf2 in nuclear fraction and the HO-1 expression in lysates. Knockdown of Nrf2 reversed the protective effects of aloperine on H2O2-induced ARPE-19 cells. In conclusion, these findings demonstrated that aloperine protected ARPE-19 cells from H2O2-induced oxidative stress and apoptosis in part via activating the Nrf2/HO-1 signaling pathway. The findings suggested a therapeutic potential of aloperine for the treatment of ADM.
C1 [Zhang, Junhui; Zhou, Haitao] HuZhou Univ, Huzhou Cent Hosp, Dept Ophthalmol, Affiliated Cent Hosp, Huzhou, Peoples R China.
   [Chen, Juanli; Lv, Xiaoyan; Liu, Hongsong] HuZhou Univ, Affiliated Cent Hosp, Huzhou Cent Hosp, Operating Room, 198 Hongqi Rd, Huzhou 313000, Peoples R China.
C3 Huzhou University; Huzhou University
RP Liu, HS (通讯作者)，HuZhou Univ, Affiliated Cent Hosp, Huzhou Cent Hosp, Operating Room, 198 Hongqi Rd, Huzhou 313000, Peoples R China.
EM hongsong_liuhz@163.com
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   Xu YQ, 2014, BIOCHEM BIOPH RES CO, V451, P568, DOI 10.1016/j.bbrc.2014.08.025
   Yang Y, 2015, SCAND J PAIN, V8, P28, DOI 10.1016/j.sjpain.2015.04.001
   Zhao J, 2018, BIOMED PHARMACOTHER, V108, P137, DOI 10.1016/j.biopha.2018.09.008
   Zhao ZY, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0019456
NR 28
TC 4
Z9 4
U1 0
U2 7
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1079-9893
EI 1532-4281
J9 J RECEPT SIG TRANSD
JI J. Recept. Signal Transduct.
PD JAN 2
PY 2022
VL 42
IS 1
BP 88
EP 94
DI 10.1080/10799893.2020.1850787
EA NOV 2020
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA YX0ML
UT WOS:000596220200001
PM 33256538
DA 2022-11-30
ER

PT J
AU Braimah, IZ
   Kenu, E
   Amissah-Arthur, KN
   Akafo, S
   Kwarteng, KO
   Amoaku, WM
AF Braimah, Imoro Zeba
   Kenu, Ernest
   Amissah-Arthur, Kwesi N.
   Akafo, Stephen
   Kwarteng, Kwaku Oppong
   Amoaku, Winfried M.
TI Safety of intravitreal ziv-aflibercept in choroido-retinal vascular
   diseases: A randomised double-blind intervention study
SO PLOS ONE
LA English
DT Article
ID DIABETIC MACULAR EDEMA; SHORT-TERM SAFETY; ANGIOGENESIS; OUTCOMES
AB Aim
   To evaluate the safety of 1.25mg and 2mg intravitreal ziv-aflibercept (IVZ) in Ghanaian eyes with choroido-retinal vascular diseases.
   Design
   Prospective, randomised, double blind, interventional study.
   Methods
   Twenty patients with centre involving macular oedema in diabetic retinopathy, retinal vein occlusion, and neovascular age-related macular degeneration were assigned to 2 groups receiving 3 doses of 1.25mg/0.05m1 (group 1) and 2mg/0.08m1 IVZ (Group 2) at 4 weekly intervals. Safety data was collected after 30 minutes, 1 and 7 days, and 4, 8 and 12 weeks after injection. Changes in continuous variables were compared using paired t-test and categorical variables were compared using chi-square test of proportions. Repeated-Measures ANOVA with nesting test was used to compare variations in continuous variables by IVZ dose over time. Primary outcome measures were ocular and systemic adverse events at 4 weeks.
   Results
   Eleven females and nine males, with mean age of 63.2 +/- 7.3 years were included. Ocular adverse events included subconjunctival haemorrhage in 1 eye, intraocular pressure (IOP) >21mmHg at 30 minutes in 6 eyes and mild pain in 3 eyes at 1-day. There was no significant difference in IOP rise between the 2 groups at 30 minutes (p = 0.21). No other ocular or systemic adverse events were observed. There was significant improvement in the best corrected visual acuity (LogMAR) from 0.95 +/- 0.6 to 0.6 +/- 0.4 (p<0.01) and 0.47 +/- 0.3 (p<0.01), reduction in central subfield foveal thickness from 405.9 +/- 140 um at baseline to 255.6 +/- 75 um (p<0.01) and 238 +/- 88 um (p<0.01) at 4 and 12 weeks respectively, although no difference was observed between the 2 groups (p = 0.34).
   Conclusion
   IVZ at 1.25mg and 2mg had similar safety profiles, and did not have any major unexpected adverse events. Further studies with larger cohorts are required to confirm efficacy.
C1 [Braimah, Imoro Zeba; Amissah-Arthur, Kwesi N.; Akafo, Stephen] Univ Ghana, Coll Hlth Sci, Sch Med & Dent, Dept Surg Eye, Accra, Ghana.
   [Braimah, Imoro Zeba; Amissah-Arthur, Kwesi N.; Akafo, Stephen; Kwarteng, Kwaku Oppong] Korle Bu Teaching Hosp, Eye Ctr, Korle Bu, Accra, Ghana.
   [Kenu, Ernest] Univ Ghana, Sch Publ Hlth, Dept Epidemiol, Accra, Ghana.
   [Amoaku, Winfried M.] Univ Nottingham, Acad Ophthalmol, Fac Med & Hlth Sci, DCN, Nottingham, England.
C3 University of Ghana; University of Ghana; University of Nottingham
RP Amoaku, WM (通讯作者)，Univ Nottingham, Acad Ophthalmol, Fac Med & Hlth Sci, DCN, Nottingham, England.
EM winfried.amoaku@nottingham.ac.uk
RI Braimah, Imoro Zeba/ABB-2168-2020
OI Braimah, Imoro Zeba/0000-0002-2573-9026; Amoaku,
   Winfried/0000-0001-5028-7984; Kenu, Ernest/0000-0001-8007-0073;
   Amissah-Arthur, Kwesi Nyan/0000-0003-2018-2043
FU Eye centre Korle-Bu Teaching Hospital
FX This work was supported by the book and research allowance of the
   principal investigator including purchase of commercially available
   zivaflibercept. The Eye centre Korle-Bu Teaching Hospital supported the
   study with imaging of the eyes involved in this study. The eye centre
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
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NR 33
TC 1
Z9 1
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 24
PY 2019
VL 14
IS 10
AR e0223944
DI 10.1371/journal.pone.0223944
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA LN0JK
UT WOS:000532631800033
PM 31647843
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Ohnesorge, N
   Sasore, T
   Hillary, D
   Alvarez, Y
   Carey, M
   Kennedy, BN
AF Ohnesorge, Nils
   Sasore, Temitope
   Hillary, Daniel
   Alvarez, Yolanda
   Carey, Michelle
   Kennedy, Breandan N.
TI Orthogonal Drug Pooling Enhances Phenotype-Based Discovery of Ocular
   Antiangiogenic Drugs in Zebrafish Larvae
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE Zebrafish; angiogenesis; eye vascular system; library screening; drug
   pooling; orthogonal pooling strategy; self-deconvoluting matrix; 3R
ID SORTING SYSTEM; SCREENS; GROWTH; IDENTIFICATION; ANGIOGENESIS;
   INHIBITORS; SUNITINIB; COMPOUND; TOXICITY; STRATEGY
AB Unbiased screening of large randomized chemical libraries in vivo is a powerful tool to find new drugs and targets. However, forward chemical screens in zebrafish can be time consuming and usually >99% of test compounds have no significant effect on the desired phenotype. Here, we sought to find bioactive drugs more efficiently and to comply with the 3R principles of replacement, reduction, and refinement of animals in research. We investigated if pooling of drugs to simultaneously test 8-10 compounds in zebrafish larvae can increase the screening efficiency of an established assay that identifies drugs inhibiting developmental angiogenesis in the eye. In a phenotype-based screen, we tested 1,760 small molecule compounds from the ChemBridge DIVERSet (TM) chemical library for their ability to inhibit the formation of distinct primary hyaloid vessels in the eye. Applying orthogonal pooling of the chemical library, we treated zebrafish embryos from 3 to 5 days post fertilization with pools of 8 or 10 compounds at 10 mu M each. This reduced the number of tests from 1,760 to 396. In 63% of cases, treatment showed sub-threshold effects of <40% reduction of primary hyaloid vessels. From 18 pool hits, we identified eight compounds that reduce hyaloid vessels in the larval zebrafish eye by at least 40%. Compound 4-[4-(1H-benzimidazol-2-yl)phenoxy] aniline ranked as the most promising candidate with reproducible and dose-dependent effects. To our knowledge, this is the first report of a self-deconvoluting matrix strategy applied to drug screening in zebrafish. We conclude that the orthogonal drug pooling strategy is a cost-effective, time-saving, and unbiased approach to discover novel inhibitors of developmental angiogenesis in the eye. Ultimately, this approach may identify new drugs or targets to mitigate disease caused by pathological angiogenesis in the eye, e.g., diabetic retinopathy or age-related macular degeneration, wherein blood vessel growth and leaky vessels lead to vision impairment or clinical blindness.
C1 [Ohnesorge, Nils; Sasore, Temitope; Alvarez, Yolanda; Kennedy, Breandan N.] Univ Coll Dublin, UCD Sch Biomol & Biomed Sci, Dublin, Ireland.
   [Ohnesorge, Nils; Sasore, Temitope; Alvarez, Yolanda; Kennedy, Breandan N.] Univ Coll Dublin, UCD Conway Inst, Dublin, Ireland.
   [Hillary, Daniel; Carey, Michelle] Univ Coll Dublin, Sch Math & Stat, Dublin, Ireland.
C3 University College Dublin; University College Dublin; University College
   Dublin
RP Kennedy, BN (通讯作者)，Univ Coll Dublin, UCD Sch Biomol & Biomed Sci, Dublin, Ireland.; Kennedy, BN (通讯作者)，Univ Coll Dublin, UCD Conway Inst, Dublin, Ireland.
EM brendan.kennedy@ucd.ie
RI kennedy, Breandan/H-5643-2019
OI kennedy, Breandan/0000-0001-7991-4689; Carey,
   Michelle/0000-0002-5603-4264
FU Marie Curie Actions Industry-Academia Partnerships and Pathways (IAPP)
   grant [612218]; Irish Research Council; European Union [734907]
FX This project was supported by and a Marie Curie Actions
   Industry-Academia Partnerships and Pathways (IAPP) grant #612218
   (3D-NET), an Irish Research Council postgraduate scholarship and the
   European Union's Horizon 2020 Research and Innovation Program under
   grant agreement No. 734907 (RISE/3D-NEONET project).
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NR 60
TC 7
Z9 7
U1 0
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD MAY 24
PY 2019
VL 10
AR 508
DI 10.3389/fphar.2019.00508
PG 10
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA HZ5UF
UT WOS:000468917500001
PM 31178719
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Chong, MFA
   Cho, HHI
   Jackson, AJ
   Bentley, SA
AF Chong, Mae F. A.
   Cho, Helen H. I.
   Jackson, A. Jonathan
   Bentley, Sharon A.
TI Profile of the Australian College of Optometry low vision clinic
SO CLINICAL AND EXPERIMENTAL OPTOMETRY
LA English
DT Article
DE blindness; demographics; low vision; magnifiers; vision impairment
ID SERVICES; BARRIERS; ACCESS
AB BackgroundMethodsThe number of Australians living with vision impairment or blindness is expected to increase substantially due to the ageing population and prevalence of age-related eye disease. In response, the Australian College of Optometry (ACO) commenced a low vision clinic in 2013. The ACO is a not-for-profit organisation providing eye-care services to more than 60,000 Victorians per year experiencing economic or social disadvantage. Consultation fees are bulk-billed to the Australian national health care scheme - Medicare - while spectacles and visual aids are subsidised through the state government-funded Victorian Eyecare Service. The aim of this study was to determine the profile and prescribing patterns of the new optometry-led low vision clinic, and report the findings of a short-term loan magnifier pilot study.
   A retrospective audit of 270 patient records was conducted. Additionally, a short-term loan magnifier program was pilot tested to ascertain the demand for, and benefits of, such a program among this cohort.
   ResultsConclusionsThe median age was 77 years (interquartile range 64 to 85 years), with 52 per cent being female. The main cause of vision impairment was age-related macular degeneration (40 per cent). At least one-third primarily spoke a language other than English. The majority (75 per cent) were referred by the optometrist to the onsite consultant occupational therapist for immediate assistance with activities of daily living and onward referral for additional comprehensive services, as required. Of the 49 participants who completed the loan magnifier study, only nine exchanged the magnifier/s initially prescribed.
   The ACO has established a low vision service within a large optometry clinic for people experiencing social and economic disadvantage. Where a program of subsidised low-cost magnifiers is available, there is little benefit to short-term loans of magnifiers. Providing basic affordable low vision aids and rehabilitation within a large primary care optometry setting can facilitate acceptability and uptake of low vision services that increase quality of life.
C1 [Chong, Mae F. A.; Cho, Helen H. I.] Australian Coll Optometry, Natl Vis Res Inst, Carlton, Vic, Australia.
   [Jackson, A. Jonathan] Royal Grp Hosp, Dept Ophthalmol & Optometry, Belfast, Antrim, North Ireland.
   [Bentley, Sharon A.] Queensland Univ Technol, Sch Optometry & Vis Sci, Kelvin Grove, Qld, Australia.
C3 Queensland University of Technology (QUT)
RP Chong, MFA (通讯作者)，Australian Coll Optometry, Natl Vis Res Inst, Carlton, Vic, Australia.
EM mchong@aco.org.au
RI Jackson, Jonathan/ABH-1264-2021
OI Jackson, Jonathan/0000-0003-4675-0272; Bentley,
   Sharon/0000-0003-0146-4248
FU Victorian Eyecare Service; ACO low vision clinic partner organisation,
   Vision Australia; Eric Ormond Baker Charitable Fund
FX The authors wish to acknowledge the ongoing support of the Victorian
   state government in funding the Victorian Eyecare Service and the ACO
   low vision clinic partner organisation, Vision Australia. Additionally,
   the authors acknowledge the contributions of Iris SY Huang for
   assistance in the establishment of the ACO LVC and loan magnifier study.
   Funding for the pilot loan magnifier program was provided by the Eric
   Ormond Baker Charitable Fund, as administered by Equity Trustees
   Limited.
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NR 22
TC 3
Z9 4
U1 1
U2 1
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0816-4622
EI 1444-0938
J9 CLIN EXP OPTOM
JI Clin. Exp. Optom.
PD NOV
PY 2018
VL 101
IS 6
BP 793
EP 798
DI 10.1111/cxo.12805
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GY7IX
UT WOS:000448783800013
PM 30021246
OA Bronze, Green Submitted
DA 2022-11-30
ER

PT J
AU Kiyama, T
   Chen, CK
   Wang, SW
   Pan, P
   Ju, ZL
   Wang, J
   Takada, S
   Klein, WH
   Mao, CA
AF Kiyama, Takae
   Chen, Ching-Kang
   Wang, Steven W.
   Pan, Ping
   Ju, Zhenlin
   Wang, Jing
   Takada, Shinako
   Klein, William H.
   Mao, Chai-An
TI Essential roles of mitochondrial biogenesis regulator Nrf1 in retinal
   development and homeostasis
SO MOLECULAR NEURODEGENERATION
LA English
DT Article
DE Mitochondria; biogenesis; Nrf1; Retinal progenitor cell; Retinal
   ganglion cell; Optic atrophy; Photoreceptor degeneration
ID RESPIRATORY-CHAIN EXPRESSION; DYNAMIN-RELATED GTPASE;
   CYTOCHROME-C-OXIDASE; GANGLION-CELL; TRANSCRIPTION FACTOR;
   GENE-EXPRESSION; NUCLEAR; FUSION; BINDING; DIFFERENTIATION
AB Background: Mitochondrial dysfunction has been implicated in the pathologies of a number of retinal degenerative diseases in both the outer and inner retina. In the outer retina, photoreceptors are particularly vulnerable to mutations affecting mitochondrial function due to their high energy demand and sensitivity to oxidative stress. However, it is unclear how defective mitochondrial biogenesis affects neural development and contributes to neural degeneration. In this report, we investigated the in vivo function of nuclear respiratory factor 1 (Nrf1), a major transcriptional regulator of mitochondrial biogenesis in both proliferating retinal progenitor cells (RPCs) and postmitotic rod photoreceptor cells (PRs).
   Methods: We used mouse genetic techniques to generate RPC-specific and rod PR-specific Nrf1 conditional knockout mouse models. We then applied a comprehensive set of tools, including histopathological and molecular analyses, RNA-seq, and electroretinography on these mouse lines to study Nrf1-regulated genes and Nrf1's roles in both developing retinas and differentiated rod PRs. For all comparisons between genotypes, a two-tailed twosample student's t-test was used.
   Results were considered significant when P < 0.05. Results: We uncovered essential roles of Nrf1 in cell proliferation in RPCs, cell migration and survival of newly specified retinal ganglion cells (RGCs), neurite outgrowth in retinal explants, reconfiguration of metabolic pathways in RPCs, and mitochondrial morphology, position, and function in rod PRs.
   Conclusions: Our findings provide in vivo evidence that Nrf1 and Nrf1-mediated pathways have context-dependent and cell-state-specific functions during neural development, and disruption of Nrf1-mediated mitochondrial biogenesis in rod PRs results in impaired mitochondria and a slow, progressive degeneration of rod PRs. These results offer new insights into the roles of Nrf1 in retinal development and neuronal homeostasis and the differential sensitivities of diverse neuronal tissues and cell types of dysfunctional mitochondria. Moreover, the conditional Nrf1 allele we have generated provides the opportunity to develop novel mouse models to understand how defective mitochondrial biogenesis contributes to the pathologies and disease progression of several neurodegenerative diseases, including glaucoma, age-related macular degeneration, Parkinson's diseases, and Huntington's disease.
C1 [Kiyama, Takae; Pan, Ping; Mao, Chai-An] Univ Texas Hlth Sci Ctr Houston UTHlth, McGovern Med Sch, Ruiz Dept Ophthalmol & Visual Sci, 6431 Fannin St,MSB 7-024, Houston, TX 77030 USA.
   [Chen, Ching-Kang] Baylor Coll Med, Dept Ophthalmol, 1 Baylor Plaza, Houston, TX 77030 USA.
   [Wang, Steven W.; Klein, William H.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
   [Ju, Zhenlin; Wang, Jing] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
   [Takada, Shinako] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
   [Takada, Shinako] NIGMS, Off Sci Review, NIH, Bethesda, MD 20892 USA.
C3 Baylor College of Medicine; University of Texas System; University of
   Texas Health Science Center Houston; Baylor College of Medicine;
   University of Texas System; UTMD Anderson Cancer Center; University of
   Texas System; UTMD Anderson Cancer Center; University of Texas System;
   UTMD Anderson Cancer Center; National Institutes of Health (NIH) - USA;
   NIH National Institute of General Medical Sciences (NIGMS)
RP Mao, CA (通讯作者)，Univ Texas Hlth Sci Ctr Houston UTHlth, McGovern Med Sch, Ruiz Dept Ophthalmol & Visual Sci, 6431 Fannin St,MSB 7-024, Houston, TX 77030 USA.
EM Takae.Kiyama@uth.tmc.edu; Chai-An.Mao@uth.tmc.edu
OI Mao, Chai-An/0000-0002-9700-6964
FU National Institutes of Health-National Eye Institute [EY024376,
   EY013811, EY022228, EY011930]; National Institute of Allergy and
   Infectious Diseases [AI057504]; National Eye Institute Vision Core Grant
   [P30EY010608]; NATIONAL EYE INSTITUTE [P30EY028102, R01EY024376,
   R01EY026930, R01EY013811, R01EY011930, R56EY013811, R01EY022228,
   P30EY010608, P30EY002520] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI057504] Funding
   Source: NIH RePORTER
FX This work was supported by grants from the National Institutes of
   Health-National Eye Institute to C.-A.M. (EY024376), C.-K.C (EY013811,
   EY022228), and W.H.K. (EY011930) and from the National Institute of
   Allergy and Infectious Diseases to S.T. (AI057504). This work was also
   supported by National Eye Institute Vision Core Grant P30EY010608
   (UTHealth).
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NR 63
TC 35
Z9 35
U1 1
U2 7
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD OCT 17
PY 2018
VL 13
AR 56
DI 10.1186/s13024-018-0287-z
PG 23
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA GX5CM
UT WOS:000447758900001
PM 30333037
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Miyahara, H
   Sawashita, J
   Ishikawa, E
   Yang, M
   Ding, X
   Liu, YY
   Hachiya, N
   Kametani, F
   Yazaki, M
   Mori, M
   Higuchi, K
AF Miyahara, Hiroki
   Sawashita, Jinko
   Ishikawa, Eri
   Yang, Mu
   Ding, Xin
   Liu, Yingye
   Hachiya, Naomi
   Kametani, Fuyuki
   Yazaki, Masahide
   Mori, Masayuki
   Higuchi, Keiichi
TI Comprehensive proteomic profiles of mouse AApoAII amyloid fibrils
   provide insights into the involvement of lipoproteins in the pathology
   of amyloidosis
SO JOURNAL OF PROTEOMICS
LA English
DT Article
DE ApoA-II; Amyloidosis; LC-MS/MS; ApoE; Clusterin; Vitronectin
ID APOLIPOPROTEIN-A-II; SENESCENCE-ACCELERATED MICE; STOP-CODON MUTATION;
   ALZHEIMERS-DISEASE; SENILE AMYLOIDOSIS; MACULAR DEGENERATION;
   MASS-SPECTROMETRY; APOA-II; EXTRACELLULAR CHAPERONES; CLUSTERIN
   EXPRESSION
AB Amyloidosis is a disorder characterized by extracellular fibrillar deposits of misfolded proteins. The amyloid deposits commonly contain several non-fibrillar proteins as amyloid-associated proteins, but their roles in amyloidosis pathology are still unknown. In mouse senile amyloidosis, apolipoprotein A-II (ApoA-II) forms extracellular amyloid fibril (AApoAII) deposits with other proteins (AApoAII-associated proteins) in many organs. We previously reported that R1.P1-Apoa.2 mice provide a reproducible model of AApoAII amyloidosis. In order to investigate the sequential alterations of AApoAII-associated protein, we performed a proteomic analysis of amyloid fibrils extracted from mouse liver tissues that contained different levels of AApoAll deposition. We identified 6 AApoAII-associated proteins that constituted 20 of the top-ranked proteins in mice with severe AApoAII deposition. Although the amount of AApoAII-associated proteins increased with the progression of amyloidosis, the relative abundance of AApoAll-associated proteins changed little throughout the progression of amyloidosis. On the other hand, plasma levels of these proteins showed dramatic changes during the progression of amyloidosis. In addition, we confirmed that AApoAII-associated proteins were significantly associated with lipid metabolism based on functional enrichment analysis, and lipids were co-deposited with AApoAII fibrils from early stages of development of amyloidosis. Thus, these results demonstrate that lipoproteins are involved in AApoAII amyloidosis pathology.
   Significance: This study presented proteomic profiles of AApoAII amyloidosis during disease progression and it revealed co-deposition of lipids with AApoAII deposits based on functional analyses. The relative abundance of AApoAII-associated proteins in the amyloid fibril fractions did not change over the course of development of AApoAII amyloidosis pathology. However, their concentrations in plasma changed dramatically with progression of the disease. Interestingly, several AApoAII-associated proteins have been found as constituents of lipid rich lesions of other degenerative diseases, such as atherosclerosis and age-related macular degeneration. The common protein components among these diseases with lipid-rich deposits could be accounted for by a lipoprotein retention model.
C1 [Miyahara, Hiroki; Sawashita, Jinko; Yang, Mu; Ding, Xin; Liu, Yingye; Mori, Masayuki; Higuchi, Keiichi] Shinshu Univ, Grad Sch Med, Inst Pathogenesis & Dis Prevent, Dept Aging Biol, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.
   [Sawashita, Jinko; Yazaki, Masahide; Higuchi, Keiichi] Shinshu Univ, Inst Biomed Sci Interdisciplinary Cluster Cutting, Dept Biol Sci Intractable Neurol Dis, Matsumoto, Nagano 3908621, Japan.
   [Ishikawa, Eri] Shinshu Univ, Res Ctr Supports Adv Sci, Div Instrumental Res, Matsumoto, Nagano 3908621, Japan.
   [Hachiya, Naomi] Tokyo Metropolitan Ind Technol Res Inst, Koto Ku, Tokyo 1350064, Japan.
   [Kametani, Fuyuki] Tokyo Metropolitan Inst Med Sci, Dept Dementia & Higher Brain Funct, Tokyo 1568506, Japan.
   [Mori, Masayuki] Shinshu Univ, Inst Biomed Sci Interdisciplinary Cluster Cutting, Dept Adv Med Hlth Promot, Matsumoto, Nagano 3908621, Japan.
C3 Shinshu University; Shinshu University; Shinshu University; Tokyo
   Metropolitan Institute of Medical Science; Shinshu University
RP Higuchi, K (通讯作者)，Shinshu Univ, Grad Sch Med, Inst Pathogenesis & Dis Prevent, Dept Aging Biol, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.
EM keiichih@shinshu-u.ac.jp
RI Kametani, Fuyuki/G-4752-2011
OI Kametani, Fuyuki/0000-0001-9125-7001; Sawashita,
   Jinko/0000-0001-8016-6649
FU Ministry of Education, Culture, Sports, Science and Technology, Japan
   [26293084, 26670152]; Grants-in-Aid for Scientific Research [26660176,
   17K08739, 17H04063, 26670152] Funding Source: KAKEN
FX This work was supported in part by Grants-in-Aid for Scientific Research
   (B) 26293084 and Challenging Exploratory Research 26670152 from the
   Ministry of Education, Culture, Sports, Science and Technology, Japan.
   The authors thank Dr. Kiyoshi Matsumoto, Dr. Takahiro Yoshizawa, Ms.
   Kayo Suzuki and Mr. Kiyokazu Kametani (Research Center for Supports to
   Advanced Science, Shinshu University) for animal care and technical
   assistance with TEM.
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NR 75
TC 9
Z9 9
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3919
EI 1876-7737
J9 J PROTEOMICS
JI J. Proteomics
PD FEB 10
PY 2018
VL 172
BP 111
EP 121
DI 10.1016/j.jprot.2017.10.003
PG 11
WC Biochemical Research Methods
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA FU2CH
UT WOS:000423655300012
PM 28988881
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Cicinelli, MV
   Carnevali, A
   Rabiolo, A
   Querques, L
   Zucchiatti, I
   Scorcia, V
   Bandello, F
   Querques, G
AF Cicinelli, Maria V.
   Carnevali, Adriano
   Rabiolo, Alessandro
   Querques, Lea
   Zucchiatti, Ilaria
   Scorcia, Vincenzo
   Bandello, Francesco
   Querques, Giuseppe
TI CLINICAL SPECTRUM OF MACULAR-FOVEAL CAPILLARIES EVALUATED WITH OPTICAL
   COHERENCE TOMOGRAPHY ANGIOGRAPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID AVASCULAR ZONE; FLUORESCEIN ANGIOGRAPHY; CENTRAL RETINA; PIT;
   RETINOPATHY; MORPHOLOGY; DIAGNOSIS
AB Purpose: To describe macular-foveal capillaries (MFC) by means of optical coherence tomography angiography and to identify the clinical spectrum of this angiographic feature.
   Methods: Patients with MFC presenting at the Medical Retina & Imaging Unit of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Patients underwent a complete ophthalmologic examination that included slit-lamp examination, fundus examination, measurement of best-corrected visual acuity, fundus auto-fluorescence, and spectral-domain optical coherence tomography (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). Fluorescein angiography was performed in selected cases. Optical coherence tomography angiography was performed through Zeiss prototype (AngioPlex, CIRRUS HD-OCT models 5000; Carl Zeiss Meditec, Inc, Dublin, OH).
   Results: Twelve eyes of 10 consecutive white patients (5 men and 5 women; 50%) presenting MFC were included. Mean age was 66.2 +/- 10.2 years (range, 53-79 years); mean best-corrected visual acuity was 0.1 +/- 0.13 logarithm of the minimum angle of resolution (range, 0-0.4 logarithm of the minimum angle of resolution, corresponding to 20/20 to 20/50). Mean central macular thickness was 348 +/- 57.6 mu m. Two patients were affected by macular pucker, two by postsurgical macular edema, two by age-related macular degeneration, one by diabetic retinopathy, one by dome-shaped macula, one presented with chronic serous chorioretinopathy, and one with branch artery occlusion. Six eyes disclosed a complete absence of the foveal avascular zone, whereas the six other cases showed a partial foveal avascularity. No significant difference was found between complete and incomplete MFC with regards to best-corrected visual acuity (P = 0.272) and central macular thickness (P = 0.870).
   Conclusion: Cases of persistent MFC are heterogeneous in demographic characteristics, fundus appearance, and visual function. However, MFC, presenting either as complete absence of the foveal avascular zone or only partial foveal avascularity, may complicate different retinal abnormalities or represents a coincident finding.
C1 [Cicinelli, Maria V.; Carnevali, Adriano; Rabiolo, Alessandro; Querques, Lea; Zucchiatti, Ilaria; Scorcia, Vincenzo; Bandello, Francesco; Querques, Giuseppe] Univ Vita Salute, Dept Ophthalmol, IRCCS Osped San Raffaele, Via Olgettina 60, I-20132 Milan, Italy.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele
RP Querques, G (通讯作者)，Univ Vita Salute, Dept Ophthalmol, IRCCS Osped San Raffaele, Via Olgettina 60, I-20132 Milan, Italy.
EM giuseppe.querques@hotmail.it
RI Rabiolo, Alessandro/J-2831-2019; bandello, francesco/AAH-2405-2019;
   Zucchiatti, Ilaria/ABA-7083-2020; cicinelli, maria vittoria/M-1611-2019
OI bandello, francesco/0000-0003-3238-9682; cicinelli, maria
   vittoria/0000-0003-2938-0409; Rabiolo, Alessandro/0000-0002-7772-5929;
   Querques, Giuseppe/0000-0002-3292-9581
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NR 37
TC 24
Z9 25
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAR
PY 2017
VL 37
IS 3
BP 436
EP 443
DI 10.1097/IAE.0000000000001199
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EQ3QM
UT WOS:000397987600013
PM 27780174
DA 2022-11-30
ER

PT J
AU Song, DL
   Song, JT
   Wang, CG
   Li, YF
   Dunaief, JL
AF Song, Delu
   Song, Jiantao
   Wang, Chenguang
   Li, Yafeng
   Dunaief, Joshua L.
TI Berberine protects against light-induced photoreceptor degeneration in
   the mouse retina
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Berberine; Light damage; Retina; Photoreceptor degeneration; Oxidative
   stress
ID CHELATOR DEFERIPRONE PROTECTS; INDUCED OXIDATIVE STRESS; SIGNALING
   PATHWAY; INDUCED APOPTOSIS; INDUCED DAMAGE; PHOTIC INJURY; KNOCKOUT
   MICE; EXPRESSION; CELL; RAT
AB Oxidative stress and inflammation play key roles in the light damage (LD) model of photoreceptor degeneration, as well as in age-related macular degeneration (AMD). We sought to investigate whether Berberine (BBR), an antioxidant herb extract, would protect the retina against light-induced degeneration. To accomplish this, Balb/c mice were treated with BBR or PBS via gavage for 7 days, and then were placed in constant cool white light-emitting diode (LED) light (10,000 lux) for 4 h. Retinal function and degeneration were evaluated by histology, electroretinography (ERG) and optical coherence tomography (OCT) at 7d after LD. Additionally, mRNA levels of cell-type specific, antioxidant, and inflammatory genes were compared 7d after LD. Photoreceptor DNA fragmentation was assessed via the terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay. LD resulted in substantial photoreceptor specific cell death. Histological analysis using plastic sections showed dosing with BBR preserved photoreceptors. The ERG analysis demonstrated functional protection by BBR in rod-b,-a, and cone-b waves. In OCT images, mice receiving PBS showed severe thinning and disorganization of the photoreceptor layer 7 days after LD, whereas mice treated with BBR had significantly less thinning and disorganization. Consistent with OCT results, the mRNA levels of Rho in the NSR, and Rpe65 and Mct3 in the RPE, were significantly higher in mice treated with BBR. The numbers of TUNEL-positive photoreceptors were significantly decreased in BBR-treated mice. The retinal mRNA levels of oxidative stress genes, the number of microglia/macrophages, and the malondialdehyde (MDA) immunolabeling were significantly lower in BBR-treated mice compared to controls 48 h after LD, which indicates oxidative stress was reduced by BBR in light-damaged eyes. In conclusion, systemic BBR is protective against light-induced retinal degeneration associated with diminished oxidative stress in the retina. These results suggest that BBR may be protective against retinal diseases involving oxidative stress. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Song, Delu; Song, Jiantao; Wang, Chenguang; Li, Yafeng; Dunaief, Joshua L.] Univ Penn, Perelman Sch Med, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
   [Song, Jiantao] China Acad Chinese Med Sci, Hosp Eye, Beijing, Peoples R China.
   [Wang, Chenguang] Jilin Univ, Hosp 2, Dept Ophthalmol, Changchun, Jilin, Peoples R China.
C3 University of Pennsylvania; Pennsylvania Medicine; China Academy of
   Chinese Medical Sciences; Jilin University
RP Dunaief, JL (通讯作者)，305 Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@mail.med.upenn.edu
OI Song, Delu/0000-0002-9030-7211
FU NIH [EY015240]; Research to Prevent Blindness; F. M. Kirby Foundation;
   Paul and Evanina Bell Mackall Foundation Trust; NATIONAL EYE INSTITUTE
   [R01EY015240, P30EY001583] Funding Source: NIH RePORTER
FX This work was supported by NIH EY015240, Research to Prevent Blindness,
   the F. M. Kirby Foundation, the Paul and Evanina Bell Mackall Foundation
   Trust, a gift in memory of Dr. Lee F. Mauger.
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NR 36
TC 19
Z9 20
U1 2
U2 15
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD APR
PY 2016
VL 145
BP 1
EP 9
DI 10.1016/j.exer.2015.10.005
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DL1DL
UT WOS:000375372300001
PM 26475979
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Limburg, H
   Espinoza, R
   Lansingh, VC
   Silva, JC
AF Limburg, Hans
   Espinoza, Rosario
   Lansingh, Van C.
   Carlos Silva, Juan
TI Functional low vision in adults from Latin America: findings from
   population-based surveys in 15 countries
SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC
   HEALTH
LA English
DT Article
DE Eye health; vision; low; cross-sectional studies; health planning;
   Argentina; Brazil; Chile; Cuba; Dominican Republic; Ecuador; El
   Salvador; Guatemala; Honduras; Mexico; Panama; Paraguay; Peru; Uruguay;
   Venezuela; Latin America; Caribbean Region
ID AVOIDABLE VISUAL IMPAIRMENT; NATIONAL-SURVEY; BLINDNESS; PREVALENCE;
   SERVICES; CATARACT
AB Objective. To review data on functional low vision (FLV) (low vision-visual acuity (VA) < 6/18 (<20/60) to >= perception of light (PL+) in the better eye-that is untreatable and uncorrectable) in adults aged 50 years or older from published population- based surveys from 15 countries in Latin America and the Caribbean.
   Methods. Data from 15 cross-sectional, population- based surveys on blindness and visual impairment (10 national and five subnational) covering 55 643 people >= 50 years old in 15 countries from 2003 to 2013 were reanalyzed to extract statistics on FLV. Eleven of the studies used the rapid assessment of avoidable blindness (RAAB) method and four used the rapid assessment of cataract surgical services (RACSS) method. For the 10 national surveys, age and sex-specific prevalence of FLV was extrapolated against the corresponding population to estimate the total number of people >= 50 years old with FLV.
   Results. Age- and sex-adjusted prevalence of FLV in people >= 50 years old ranged from 0.9% (Guatemala, Mexico, and Uruguay) to 2.2% (Brazil and Cuba) and increased by age. The weighted average prevalence for the 10 national surveys was 1.6%:1.4% in men and 1.8% in women. For all 10 national studies, a total of 509 164 people >= 50 years old were estimated to have FLV. Based on the 910 individuals affected, the main causes of FLV were age-related macular degeneration (weighted average prevalence of 26%), glaucoma (23%), diabetic retinopathy (19%), other posterior segment disease (15%), non-trachomatous corneal opacities (7%), and complications after cataract surgery (4%).
   Conclusions. FLV is expected to rise because of 1) the exponential increase of this condition by age, 2) increased life expectancy, and 3) the increase in people >= 50 years old. These data can be helpful in planning and developing low vision services for the region; large countries such as Brazil and Mexico would need more studies. Prevention is a major strategy to reduce FLV, as more than 50% of it is preventable.
C1 [Limburg, Hans] London Sch Hyg & Trop Med, Int Ctr Eye Hlth, London WC1, England.
   [Espinoza, Rosario] Univ Peruana Cayetano Heredia, Lima, Peru.
   [Lansingh, Van C.] Inst Mexicano Oftalmol, Queretaro, Queretaro, Mexico.
   [Carlos Silva, Juan] Pan Amer Hlth Org, Bogota, Colombia.
C3 University of London; London School of Hygiene & Tropical Medicine;
   Universidad Peruana Cayetano Heredia; Pan American Health Organization
RP Limburg, H (通讯作者)，London Sch Hyg & Trop Med, Int Ctr Eye Hlth, London WC1, England.
EM hlimburg@quicknet.nl
RI Silva, Juan Carlos/N-9113-2019; Lansingh, Van/C-8672-2018
OI Silva, Juan Carlos/0000-0003-4855-5008; Lansingh,
   Van/0000-0002-0090-4195
FU PAHO; Orbis International (New York)
FX This publication was funded by grants from PAHO and Orbis International
   (New York).
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NR 30
TC 11
Z9 12
U1 0
U2 9
PU PAN AMER HEALTH ORGANIZATION
PI WASHINGTON
PA 525 23RD ST NW, WASHINGTON, DC 20037 USA
SN 1020-4989
J9 REV PANAM SALUD PUBL
JI Rev. Panam. Salud Publica
PD JUN
PY 2015
VL 37
IS 6
BP 371
EP 378
PG 8
WC Public, Environmental & Occupational Health
WE Social Science Citation Index (SSCI)
SC Public, Environmental & Occupational Health
GA CO7CI
UT WOS:000359314700001
PM 26245171
DA 2022-11-30
ER

PT J
AU Rozanski, C
   Haythornthwaite, JA
   Dagnelie, G
   Bittner, AK
AF Rozanski, Collin
   Haythornthwaite, Jennifer A.
   Dagnelie, Gislin
   Bittner, Ava K.
TI Applying theories and interventions from behavioral medicine to
   understand and reduce visual field variability in patients with vision
   loss
SO MEDICAL HYPOTHESES
LA English
DT Article
ID QUALITY-OF-LIFE; NORMAL-TENSION GLAUCOMA; OPEN-ANGLE GLAUCOMA;
   RETINITIS-PIGMENTOSA; MACULAR DEGENERATION; ALTERNATIVE MEDICINE; OCULAR
   HYPERTENSION; AUTOMATED PERIMETRY; COGNITIVE THERAPY; MEASURING RATES
AB Visual field (VF) test results are often unreliable in visually impaired patients, but continue to be a cornerstone of clinical trials and play a vital role in clinical decision making since they are the primary method to determine patients' functional vision loss or progression. Currently, patients are typically asked to perform VF tasks with minimal instruction or consideration of their psychological experience during the test. The gradual loss of vision due to retinal diseases, such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), or glaucoma can contribute to the experience of negative psychosocial states, such as anxiety, stress, and depression, as well as diminished quality of life. We hypothesize that VF testing elicits test performance anxiety and perception of functional losses of vision, which induces distracting negative thoughts that result in increased VF test variability. Resources for processing and responding to vision-related information may be diverted from task-relevant VF stimuli to task-irrelevant ones, such as internal worry and test anxiety, thereby resulting in VF test performance decrements. We present a theoretical model to support the hypothesis that VF variability is linked to patients' negative thoughts during VF testing. This conceptual framework provides a basis for the development of coping strategies and mindfulness-based interventions to be evaluated in future research aimed at improving psychosocial states and VF reliability in visually-impaired patients. It would be highly significant to intervene by modifying negative thoughts during VF testing to reduce test variability in glaucoma patients who are progressively losing vision to a blinding eye disease, but whose vision loss has not been accurately identified and treated early enough due to variable VF results. In clinical trials of potential interventions for RP and non-neovascular AMD, reducing VF variability would effectively increase the precision for detecting treatment effects and allow a reduction in the number of VF tests needed to estimate the treatment responses, thus reducing burden on investigators and patients, as well as saving time and money. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Rozanski, Collin] Johns Hopkins Univ, Baltimore, MD 21218 USA.
   [Haythornthwaite, Jennifer A.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA.
   [Dagnelie, Gislin] Johns Hopkins Univ, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21218 USA.
   [Bittner, Ava K.] Nova SE Univ, Coll Optometry, Ft Lauderdale, FL 33314 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins
   University; Johns Hopkins Medicine; Nova Southeastern University
RP Bittner, AK (通讯作者)，3200 Univ Dr, Ft Lauderdale, FL 33328 USA.
EM abittner@nova.edu
RI Bittner, Ava/AAK-8778-2021
OI Bittner, Ava/0000-0002-9498-2230
FU NIH [K23 EY018356]; NATIONAL EYE INSTITUTE [K23EY018356] Funding Source:
   NIH RePORTER
FX This work was funded by NIH Grant K23 EY018356 to A.K.B. The grant
   sponsor had no involvement in this paper.
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NR 63
TC 7
Z9 7
U1 1
U2 9
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
   LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
EI 1532-2777
J9 MED HYPOTHESES
JI Med. Hypotheses
PD AUG
PY 2014
VL 83
IS 2
BP 190
EP 195
DI 10.1016/j.mehy.2014.04.031
PG 6
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Research & Experimental Medicine
GA AL4YS
UT WOS:000339141300013
PM 24854574
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Murthy, RK
   Ravi, K
   Balaiya, S
   Brar, VS
   Chalam, KV
AF Murthy, Ravi K.
   Ravi, Kavitha
   Balaiya, Sankarathi
   Brar, Vikram S.
   Chalam, Kakarla V.
TI Lutein protects retinal pigment epithelium from cytotoxic oxidative
   stress
SO CUTANEOUS AND OCULAR TOXICOLOGY
LA English
DT Article
DE Carotenoids; macular degeneration; oxidative stress; retinal pigment
   epithelium
ID ZEAXANTHIN; APOPTOSIS; ARPE-19; DAMAGE; LINE
AB Context: Lutein (LUT) and zeaxanthin (ZEA) are currently under investigation in clinical trials as prophylactic nutritional agents for age-related macular degeneration (AMD). However, dose used in these trials is empirical and not been investigated in in vitro studies.
   Objective: In this study, we investigated the dose-response effect of LUT and ZEA in protecting retinal pigment epithelium (RPE) from oxidative stress, a common underlying pathology in AMD.
   Methods: Three thousand cultured human retinal pigment epithelial cells (ARPE-19) were plated in 72-well plate and after 24 h were exposed to increasing concentrations of hydrogen peroxide (H2O2). ARPE-19 cells were exposed to four different concentrations of LUT (0.5, 1, 2 and 4 mu g/mL) and ZEA (0.1, 0.2, 0.4 and 0.8 mu g/mL). After 24 h incubation, cells were subjected to oxidative stress induced with H2O2. Cultures containing saline solution and dichloromethane served as controls. Cell viability was assessed using the WST-1 assay. Pathophysiological pathways were evaluated by measuring caspase-3 levels as an indicator of apoptosis induction. Reactive oxygen species (ROS) levels were measured using dihydrorhodamine-123.
   Results: Cell viability as a percentage of control was 81.3%, 81.1%, and 88.8% at 0.5, 1, and 2 mu g/ml, respectively of LUT (p<0.001). The maximum cytoprotective effect was seen with LUT at 2 mu g/mL. ZEA did not show any cytoprotective effect at all concentrations used in the study. Caspase-3 showed a corresponding decrease in levels with LUT (1 and 2 mu g/ml). Significant decrease in ROS levels were measured only with LUT at 4 mu g/ml (p = 0.02).
   Discussion and conclusions: Results from our study provide in vitro data to support the epidemiologic studies, which are currently underway to provide evidence that lutein may act as cofactor that modulates processes implicated in AMD pathogenesis.
C1 [Murthy, Ravi K.; Ravi, Kavitha; Balaiya, Sankarathi; Chalam, Kakarla V.] Univ Florida, Coll Med, Dept Ophthalmol, Jacksonville, FL 32209 USA.
   [Brar, Vikram S.] Virginia Commonwealth Univ, Dept Ophthalmol, Richmond, VA USA.
C3 State University System of Florida; University of Florida; Virginia
   Commonwealth University
RP Murthy, RK (通讯作者)，Univ Florida, Coll Med, Dept Ophthalmol, 580 W,8th St,Tower 2, Jacksonville, FL 32209 USA.
EM ravi.keshavamurthy@jax.ufl.edu
RI Chalam, kakarla/K-7507-2019
OI Chalam, K V/0000-0002-0004-9416
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NR 22
TC 27
Z9 29
U1 1
U2 35
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1556-9527
EI 1556-9535
J9 CUTAN OCUL TOXICOL
JI Cutan. Ocul. Toxicol.
PD JUN
PY 2014
VL 33
IS 2
BP 132
EP 137
DI 10.3109/15569527.2013.812108
PG 6
WC Ophthalmology; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Toxicology
GA AI3AV
UT WOS:000336731700011
PM 23862688
DA 2022-11-30
ER

PT J
AU Schwartz, DM
   Fingler, J
   Kim, DY
   Zawadzki, RJ
   Morse, LS
   Park, SS
   Fraser, SE
   Werner, JS
AF Schwartz, Daniel M.
   Fingler, Jeff
   Kim, Dae Yu
   Zawadzki, Robert J.
   Morse, Lawrence S.
   Park, Susanna S.
   Fraser, Scott E.
   Werner, John S.
TI Phase-Variance Optical Coherence Tomography A Technique for Noninvasive
   Angiography
SO OPHTHALMOLOGY
LA English
DT Article
ID HIGH-SPEED; HUMAN EYE; FLOW; OCT; CONTRAST; RETINA; VISUALIZATION;
   FLUORESCEIN; MICROVASCULATURE; VASCULATURE
AB Purpose: Phase-variance optical coherence tomography (PV-OCT) provides volumetric imaging of the retinal vasculature without the need for intravenous injection of a fluorophore. We compare images from PV-OCT and fluorescein angiography (FA) for normal individuals and patients with age-related macular degeneration (AMD) and diabetic retinopathy.
   Design: This is an evaluation of a diagnostic technology.
   Participants: Four patients underwent comparative retinovascular imaging using FA and PV-OCT. Imaging was performed on 1 normal individual, 1 patient with dry AMD, 1 patient with exudative AMD, and 1 patient with nonproliferative diabetic retinopathy.
   Methods: Fluorescein angiography imaging was performed using a Topcon Corp (Tokyo, Japan) (TRC-50IX) camera with a resolution of 1280 (H) x 1024 (V) pixels. The PV-OCT images were generated by software data processing of the entire cross-sectional image from consecutively acquired B-scans. Bulk axial motion was calculated and corrected for each transverse location, reducing the phase noise introduced from eye motion. Phase variance was calculated through the variance of the motion-corrected phase changes acquired within multiple B-scans at the same position. Repeating these calculations over the entire volumetric scan produced a 3-dimensional PV-OCT representation of the vasculature.
   Main Outcome Measures: Feasibility of rendering retinal and choroidal microvasculature using PV-OCT was compared qualitatively with FA, the current gold standard for retinovascular imaging.
   Results: Phase-variance OCT noninvasively rendered a 2-dimensional depth color-coded vasculature map of the retinal and choroidal vasculature. The choriocapillaris was imaged with better resolution of microvascular detail using PV-OCT. Areas of geographic atrophy and choroidal neovascularization imaged by FA were depicted by PV-OCT. Regions of capillary nonperfusion from diabetic retinopathy were shown by both imaging techniques; there was not complete correspondence between microaneurysms shown on FA and PV-OCT images.
   Conclusions: Phase-variance OCT yields high-resolution imaging of the retinal and choroidal microvasculature that compares favorably with FA. (C) 2014 by the American Academy of Ophthalmology.
C1 [Schwartz, Daniel M.] Univ Calif San Francisco, Dept Ophthalmol & Vis Sci, San Francisco, CA 94143 USA.
   [Fingler, Jeff; Kim, Dae Yu; Fraser, Scott E.] CALTECH, Dept Biol, Pasadena, CA 91125 USA.
   [Kim, Dae Yu; Zawadzki, Robert J.; Morse, Lawrence S.; Park, Susanna S.; Werner, John S.] Univ Calif Davis, Dept Ophthalmol & Vis Sci, Davis, CA 95616 USA.
C3 University of California System; University of California San Francisco;
   California Institute of Technology; University of California System;
   University of California Davis
RP Schwartz, DM (通讯作者)，Univ Calif San Francisco, Box 0730, San Francisco, CA 94143 USA.
EM danschwartz7@gmail.com
RI Zawadzki, Robert J./S-3236-2019; Fraser, Scott/Y-3406-2019; Zawadzki,
   Robert/E-7534-2011
OI Zawadzki, Robert J./0000-0002-9574-156X; Fraser,
   Scott/0000-0002-5377-0223; Zawadzki, Robert/0000-0002-9574-156X; Morse,
   Lawrence/0000-0002-1758-2348
FU National Eye Institute [EY 014743]; Research to Prevent Blindness;
   Beckman Institute; That Man May See Foundation; Howard Hughes Medical
   Institute Med-into-Grad Initiative [56006769]; NATIONAL EYE INSTITUTE
   [R01EY014743, R01EY024239] Funding Source: NIH RePORTER
FX Supported by the National Eye Institute (EY 014743), Research to Prevent
   Blindness, Beckman Institute, That Man May See Foundation, and Howard
   Hughes Medical Institute Med-into-Grad Initiative (56006769). The
   sponsors and funding agencies had no role in the design or conduct of
   this research.
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NR 34
TC 181
Z9 193
U1 0
U2 42
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JAN
PY 2014
VL 121
IS 1
BP 180
EP 187
DI 10.1016/j.ophtha.2013.09.002
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 282KG
UT WOS:000329169500032
PM 24156929
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Mones, J
   Biarnes, M
   Trindade, F
   Arias, L
   Alonso, J
AF Mones, Jordi
   Biarnes, Marc
   Trindade, Fabio
   Arias, Luis
   Alonso, Jordi
TI Optical Coherence Tomography Assessment of Apparent Foveal Swelling in
   Patients with Foveal Sparing Secondary to Geographic Atrophy
SO OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; VISUAL-ACUITY LOSS; MACULAR DEGENERATION;
   IN-VIVO; PREVALENCE; CONE; VULNERABILITY; RANIBIZUMAB; DYSFUNCTION;
   SCOTOMAS
AB Objective: To determine whether foveal swelling exists in patients with foveal sparing and geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD) and to establish the contribution of different foveal layers to this condition by use of spectral-domain optical coherence tomography (SD-OCT).
   Design: Prospective comparative case series.
   Participants: We assessed patients from a longitudinal study with foveal sparing and GA secondary to AMD. Of an initial sample of 108 patients, 13 eyes of 10 patients complied with the inclusion criteria to study eyes in which apparent swelling would not be questionable. We used a control group of 13 healthy patients to compare the outcome measurements.
   Methods: We acquired high-resolution SD-OCT horizontal and oblique B-scans centered at the umbo. Two retinal specialists (J.M., F.T.) independently classified the SD-OCT images.
   Main Outcome Measures: Difference in foveal center thickness, apparent outer nuclear layer (ONL) thickness, ONL thickness without Henle's fiber layer (HFL), sub-ONL thickness, and retinal thickness at 1000 mu m and 3500 mu m from the foveal center.
   Results: The thickness at the foveal center was similar between patients with apparent foveal swelling (cases) and controls without AMD (226 vs. 227 mu m; P = 0.56), but the apparent ONL was thicker in cases than in controls (125 vs. 114 mu m; P = 0.02). However, when HFL was excluded from the measurements, there was little difference in the results (74 vs. 73 mu m; P = 0.82).
   Conclusions: We found neither foveal nor ONL swelling in this study. We observed HFL thickening in foveal sparing secondary to GA, which might be related to swelling of the axons of the photoreceptors, or Muller's cells. We also observed thinning of the retina below the external limiting membrane. The clinical significance of these findings should be addressed by longitudinal studies and may have specific therapeutic implications.
   Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2013;120:829-836 (C) 2013 by the American Academy of Ophthalmology.
C1 [Mones, Jordi; Biarnes, Marc; Trindade, Fabio] Inst Macula & Retina, Ctr Med Teknon, Barcelona 08021, Spain.
   [Mones, Jordi] Barcelona Macula Fdn, Barcelona, Spain.
   [Biarnes, Marc; Alonso, Jordi] Pompeu Fabra Univ, Expt Sci & Hlth Dept, Barcelona, Spain.
   [Arias, Luis] Bellvitge Hosp, Barcelona, Spain.
   [Alonso, Jordi] Hosp del Mar, Res Inst, IMIM, Hlth Serv Res Unit, Barcelona, Spain.
   [Alonso, Jordi] CIBERESP, Barcelona, Spain.
C3 Pompeu Fabra University; Institut d'Investigacio Biomedica de Bellvitge
   (IDIBELL); Bellvitge University Hospital; University of Barcelona;
   Institut Hospital del Mar d'Investigacions Mediques (IMIM); Hospital del
   Mar; CIBER - Centro de Investigacion Biomedica en Red; CIBERESP
RP Mones, J (通讯作者)，Inst Macula & Retina, Ctr Med Teknon, Vilana 12, Barcelona 08021, Spain.
EM jmones@institutmacularetina.com
RI mones, jordi/CAJ-2963-2022; Alonso, Jordi/A-5514-2010
OI mones, jordi/0000-0003-3685-2160; Alonso, Jordi/0000-0001-8627-9636;
   ARIAS, LUIS/0000-0001-7041-5576; Trindade, Fabio/0000-0001-9993-5188;
   Biarnes, Marc/0000-0003-2584-4894
FU Institut de la Macula i de la Retina; Barcelona Macula Foundation, Spain
FX The authors acknowledge Ruthline Laylor of Chameleon Communications
   International, who provided assistance with the editing of scientific
   content, with funding from the Institut de la Macula i de la Retina and
   the Barcelona Macula Foundation, Spain.
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NR 39
TC 7
Z9 8
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD APR
PY 2013
VL 120
IS 4
BP 829
EP 836
DI 10.1016/j.ophtha.2012.09.054
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 122UL
UT WOS:000317343500028
PM 23290986
DA 2022-11-30
ER

PT J
AU Chen, B
   Pogue, BW
   Hoopes, PJ
   Hasan, T
AF Chen, Bin
   Pogue, Brian W.
   Hoopes, P. Jack
   Hasan, Tayyaba
TI Vascular and cellular targeting for photodynamic therapy
SO CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION
LA English
DT Review
DE photodynamic therapy (PDT); photosensitizer; vascular targeting;
   cellular targeting; targeted therapy; drug delivery
ID MOUSE-TUMOR MODEL; GROWTH-FACTOR RECEPTOR; ASPARTYL CHLORIN E6;
   EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; INTERNALIZING
   MONOCLONAL-ANTIBODIES; WATER-SOLUBLE PHOTOSENSITIZER; ETHYL ETIOPURPURIN
   SNET2; OVARIAN-CANCER MODEL; OF-THE-ART; IN-VIVO
AB Photodynamic therapy (PDT) involves the combination of photosensitizers (PS) with light as a treatment, and has been an established medical practice for about 10 years. Current primary applications of PDT are age-related macular degeneration (AMD) and several types of cancer and precancer. Tumor vasculature and parenchyma cells are both potential targets of PDT damage. The preference of vascular versus cellular targeting is highly dependent upon the relative distribution of photosensitizers in each compartment, which is governed by the photosensitizer pharmacokinetic properties and can be effectively manipulated by the photosensitizer drug administration and light illumination interval (drug-light interval) during PDT treatment, or by the modification of photosensitizer molecular structure. PDT using shorter PS-light intervals mainly targets tumor vasculature by confining photosensitizer localization within blood vessels, whereas if the sensitizer has a reasonably long pharmacokinetic lifetime, then PDT at longer PS-light intervals can induce more tumor cellular damage, because the photosensitizer has then distributed into the tumor cellular compartment. This passive targeting mechanism is regulated by the innate photosensitizer physicochemical properties. In addition to the passive targeting approach, active targeting of various tumor endothelial and cellular markers has been studied extensively. The tumor cellular markers that have been explored for active photodynamic targeting are mainly tumor surface markers, including growth factor receptors, low-density lipoprotein (LDL) receptors, transferrin receptors, folic acid receptors, glucose transporters, integrin receptors, and insulin receptors. In addition to tumor surface proteins, nuclear receptors are targeted, as well. A limited number of studies have been performed to actively target tumor endothelial markers (ED-B domain of fibronectin, VEGF receptor-2, and neuropilin-1). Intracellular targeting is a challenge due to the difficulty in achieving sufficient penetration into the target cell, but significant progress has been made in this area. In this review, we summarize current studies of vascular and cellular targeting of PDT after more than 30 years of intensive efforts.
C1 Harvard Univ, Wellman Ctr Photomed, Dept Dermatol, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA.
   Univ Sci Philadelphia, Coll Pharm, Dept Pharmaceut Sci, Philadelphia, PA 19104 USA.
   Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.
   Dartmouth Med Sch, Dept Surg, Lebanon, NH 03756 USA.
C3 Harvard University; Harvard Medical School; Massachusetts General
   Hospital; Dartmouth College; Dartmouth College
RP Hasan, T (通讯作者)，Harvard Univ, Wellman Ctr Photomed, Dept Dermatol, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA.
EM thasan@partners.org
RI Pogue, Brian/AAD-8114-2020
OI Pogue, Brian/0000-0002-9887-670X; Hasan, Tayyaba/0000-0003-0871-6057
FU NATIONAL CANCER INSTITUTE [P01CA084203] Funding Source: NIH RePORTER;
   NCI NIH HHS [P01CA84203] Funding Source: Medline
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NR 158
TC 178
Z9 187
U1 6
U2 93
PU BEGELL HOUSE INC
PI DANBURY
PA 50 NORTH ST, DANBURY, CT 06810 USA
SN 1045-4403
EI 2162-6502
J9 CRIT REV EUKAR GENE
JI Crit. Rev. Eukaryot. Gene Expr.
PY 2006
VL 16
IS 4
BP 279
EP 305
DI 10.1615/CritRevEukarGeneExpr.v16.i4.10
PG 27
WC Biotechnology & Applied Microbiology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 113PD
UT WOS:000242608900001
PM 17206921
DA 2022-11-30
ER

PT J
AU Patton, N
   Aslam, TM
   MacGillivray, T
   Deary, IJ
   Dhillon, B
   Eikelboom, RH
   Yogesan, K
   Constable, IJ
AF Patton, N
   Aslam, TM
   MacGillivray, T
   Deary, IJ
   Dhillon, B
   Eikelboom, RH
   Yogesan, K
   Constable, IJ
TI Retinal image analysis: Concepts, applications and potential
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
ID DIGITAL FUNDUS PHOTOGRAPHY; BLOOD-VESSEL WIDTH; DIABETIC-RETINOPATHY;
   ATHEROSCLEROSIS RISK; AUTOMATED DETECTION; MICROVASCULAR ABNORMALITIES;
   FRACTAL ANALYSIS; OPTIC-NERVE; ARTERIAL TREE; CARDIOVASCULAR-DISEASE
AB As digital imaging and Computing power increasingly develop, so too does the potential to use these technologies in ophthalmology. Image processing, analysis and computer vision techniques are increasing in prominence in all fields of medical science, and are especially pertinent to modern ophthalmology, as it is heavily dependent on Visually oriented signs. The retinal microvasculature is unique in that it is the only part of the human circulation that can be directly visualised non-invasively in vivo, readily photographed and subject to digital image analysis. Exciting developments in image processing relevant to ophthalmology over the past 15 years includes the progress being made towards developing automated diagnostic systems for conditions, Such as diabetic retinopathy, age-related macular degeneration and retinopathy of prematurity. These diagnostic systems offer the potential to be used in large-scale screening programs, with the potential for significant resource savings, as well as being free from observer bias and fatigue. In addition, quantitative measurements of retinal vascular topography using digital image analysis from retinal photography have been used as research tools to better understand the relationship between the retinal microvasculature and cardiovascular disease. Furthermore, advances in electronic media transmission increase the relevance of using image processing in 'teleophthalmology' as an aid in clinical decision-making, with particular relevance to large rural-based communities.
   In this review, we outline the principles upon which retinal digital image analysis is based. We discuss current techniques used to automatically detect landmark features of the fundus, Such as the optic disc, fovea and blood vessels. We review the use of image analysis in the automated diagnosis of pathology (with particular reference to diabetic retinopathy). We also review its role in defining and performing quantitative measurements of vascular topography, how these entities are based on 'optimisation' principles and how they have helped to describe the relationship between systemic cardiovascular disease and retinal vascular changes. We also review the potential future use of fundal image analysis in telemedicine. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Lions Eye Inst, Nedlands, WA 6009, Australia.
   Princess Alexandra Eye Pavil, Edinburgh EH3 9HA, Midlothian, Scotland.
   Manchester Royal Eye Hosp, Manchester M13 9WH, Lancs, England.
   Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH4 2XU, Midlothian, Scotland.
   Univ Edinburgh, Sch Philosophy Psychol & Language Sci, Edinburgh EH8 9JU, Midlothian, Scotland.
   Sir Charles Gairdner Hosp, Lions Ear & Hearing Inst, Nedlands, WA 6009, Australia.
   Univ Western Australia, Ctr Ophthalmol & Visual Sci, Nedlands, WA 6009, Australia.
C3 Lions Eye Institute; University of Western Australia; Manchester Royal
   Eye Hospital; University of Edinburgh; University of Edinburgh;
   University of Western Australia; University of Western Australia
RP Patton, N (通讯作者)，Lions Eye Inst, 2 Verdun St, Nedlands, WA 6009, Australia.
EM niallpatton@hotmail.com
RI Deary, Ian J/C-6297-2009; Eikelboom, Robert/B-2820-2013; Kanagasingam,
   Yogesan/C-4631-2011; Aslam, Tariq/A-8532-2016
OI Deary, Ian J/0000-0002-1733-263X; Eikelboom, Robert/0000-0003-2911-5381;
   Kanagasingam, Yogesan/0000-0001-7321-7495; constable,
   ian/0000-0002-2140-6478; Aslam, Tariq/0000-0002-9739-7280; MacGillivray,
   Tom/0000-0001-5120-0086
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NR 232
TC 421
Z9 435
U1 0
U2 77
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD JAN
PY 2006
VL 25
IS 1
BP 99
EP 127
DI 10.1016/j.preteyeres.2005.07.001
PG 29
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 989SA
UT WOS:000233692900005
PM 16154379
DA 2022-11-30
ER

PT J
AU Cahill, MT
   Mruthyunjaya, P
   Rickman, CB
   Toth, CA
AF Cahill, MT
   Mruthyunjaya, P
   Rickman, CB
   Toth, CA
TI Recurrence of retinal pigment epithelial changes after macular
   translocation with 360 degrees peripheral retinectomy for geographic
   atrophy
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; VISUAL FUNCTION
AB Objective: To assess the prevalence of recurrence of macular geographic atrophy (GA) of the retinal pigment epithelium (RPE) after macular translocation with 360 degrees retinectomy (MT360) in one institution.
   Methods: A retrospective review of all cases of GA that were treated with MT360 in I institution. Demographic and clinical data including the duration of preoperative visual loss, preoperative and postoperative visual acuity, and the prevalence of postoperative foveal RPE atrophy were recorded for these patients, and these data were compared with similar data from patients who underwent MT360 for neovascular age-related macular degeneration (AMD) as part of the prospective Duke Macular Translocation Study, Duke University Eye Center, Durham, NC.
   Results: Four eyes in 4 patients with GA secondary to AMD underwent MT360 and were compared with 63 eyes in 63 patients who underwent MT360 for neovascular AMD as part of the Duke Macular Translocation Study. The mean duration of preoperative visual loss was higher in the GA group (11.3 months) than in the neovascular AMD group (1.7 months) (P=.08). The prevalence of postoperative foveal RPE atrophy was significantly higher in the GA group (n= 3; 75.0%) than in the neovascular AMD group (n=5; 8.3%) (P <.01); in the GA group, this corresponded to recurrence of the GA lesions. In contrast, the postoperative RPE atrophy seen in the neovascular AMD group was due to postoperative mechanical forces such as laser therapy or RPE tearing. There was no significant difference in the mean preoperative or postoperative visual acuity in either group.
   Conclusions: Subfoveal RPE atrophy can reoccur following MT360 in eyes with nonneovascular AMD and GA; RPE atrophy similar to this has not been found in a large consecutive series of patients with neovascular AMD after MT360. Further research is needed to assess if the potential for visual recovery in eyes with end-stage nonneovascular AMD is outweighed by the possibility of postoperative recurrence of GA.
C1 Duke Univ, Ctr Eye, Durham, NC 27710 USA.
C3 Duke University
RP Toth, CA (通讯作者)，Duke Univ, Ctr Eye, POB 3802,Erwin Rd, Durham, NC 27710 USA.
EM toth0004@mc.duke.edu
RI Toth, Cynthia/L-5534-2019; toth, cynthia a/F-5614-2011
OI Toth, Cynthia/0000-0002-2324-0854; Bowes Rickman,
   Catherine/0000-0002-8555-9596; mruthyunjaya, prithvi/0000-0003-1087-9736
FU NEI NIH HHS [R01 EY 11286, R01 EY011286] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [R01EY011286] Funding Source: NIH RePORTER
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NR 14
TC 41
Z9 42
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0003-9950
EI 1538-3601
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD JUL
PY 2005
VL 123
IS 7
BP 935
EP 938
DI 10.1001/archopht.123.7.935
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 943KR
UT WOS:000230352900006
PM 16009834
OA Bronze
DA 2022-11-30
ER

PT J
AU Talks, SJ
   Setty, R
   Clarke, L
AF Talks, SJ
   Setty, R
   Clarke, L
TI The incidence and outcome of photodynamic therapy for macular
   degeneration in the Northern Region of the UK
SO EYE
LA English
DT Article
DE age-related macular degeneration; photodynamic therapy; incidence;
   outcome
ID AGE-RELATED MACULOPATHY; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION;
   PREVALENCE; VERTEPORFIN; DISEASE
AB Purpose To assess the patients who have had photodynamic therapy (PDT) in the Northern region of the UK, in relation to the eligibility criteria found to benefit in the TAP study ( treatment of age-related macular degeneration with photodynamic therapy study), so as to make an estimate of the number of patients who might benefit from this treatment and to present the outcome of the treatment so far.
   Method The records and fluorescein angiograms (FFAs) of all patients who had had PDT in the Northern region between 2001 and 2002 were reviewed for compliance with the TAP criteria of >50% classic choroidal neovascularization and >34 letters on the 2 m logMAR Early Treatment Diabetic Retinopathy Study chart. NHS funding has been available in the Northern Region since January 2001 for 'second eye' involvement. A review of all the angiograms performed for exudative macular degeneration in 1 year was also performed. The visual outcome of those patients 1 year from baseline was measured.
   Results A total of 82 'second eye' patients were treated between January 2001 and December 2002. This gives an incidence of 65 per 3 million and so about 1300 in the whole of the UK ( population 60 million). In all, 238 FFAs were performed on exudative macular degeneration, with 21% being found eligible for PDT. As of February 2003, 54 TAP criteria, macular degeneration patients were 1 year from initial treatment. Of these, 12 had incomplete follow-up and 13 patients had lost more than 15 letters. The responder rate defined as losing <15 letters was 42 - 13/ 42 = 69%. Seven of those who did not make 1-year follow-up had lost more than 15 letters when last seen, giving a responder rate of 54 - 20/54 = 63%.
   Conclusion There may not be as many patients eligible for PDT, using the TAP criteria, as previously hoped. The outcome of treatment appears similar to that found in the TAP study.
C1 Royal Victoria Infirm, Dept Ophthalmol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
C3 Newcastle University - UK
RP Talks, SJ (通讯作者)，Royal Victoria Infirm, Dept Ophthalmol, Queen Victoria Rd, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
EM James.Talks@ncl.ac.uk
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NR 21
TC 7
Z9 7
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD JUN
PY 2004
VL 18
IS 6
BP 588
EP 594
DI 10.1038/sj.eye.6700709
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 827EP
UT WOS:000221882200008
PM 15184924
OA Bronze
DA 2022-11-30
ER

PT J
AU Chen, QQ
   Xin, G
   Li, SY
   Dong, YM
   Yu, XX
   Wan, CY
   Wei, ZL
   Zhu, YD
   Zhang, K
   Wang, YL
   Li, F
   Zhang, CC
   Wen, E
   Li, YL
   Niu, H
   Huang, W
AF Chen, Qingqiu
   Xin, Guang
   Li, Shiyi
   Dong, Yuman
   Yu, Xiuxian
   Wan, Chengyu
   Wei, Zeliang
   Zhu, Yuda
   Zhang, Kun
   Wang, Yilan
   Li, Fan
   Zhang, Cuicui
   Wen, E.
   Li, Yulong
   Niu, Hai
   Huang, Wen
TI Berberine-mediated REDD1 down-regulation ameliorates senescence of
   retinal pigment epithelium by interrupting the ROS-DDR positive feedback
   loop
SO PHYTOMEDICINE
LA English
DT Article
DE Berberine; Retinal pigment epithelium; REDD1; Senescence; Autophagic
   flux
ID OXIDATIVE STRESS; HYPOXIA; RTP801; GENE
AB Background: Accumulation of age-associated senescent cells accompanied with increased reactive oxygen species (ROS) and inflammatory factors contributes to the progression of age-related macular degeneration (AMD), the main cause of blindness in the elderly. Berberine (BBR) has shown efficacy in the treatment of age-related diseases including diabetes and obesity by decreasing ROS. However, the pharmacological effect of BBR on alleviating retinal aging remains largely unknown.Purpose: Our study aimed to investigate the pharmacological effect of BBR as an anti-aging agent in retinal aging and its further molecular mechanisms.Methods: D-galactose (DG)-induced ARPE-19 cell senescence and retinal aging were employed to evaluate the anti-aging effect of BBR in vivo and in vitro. The siRNA transfection, Western-Blot analyses, SA-beta-Gal assay and immunofluorescence were performed to investigate the potential mechanisms of BBR on anti-aging of RPE. Results: In RPE-choroid of both natural aged and DG-induced accelerated aged mice, oxidative stress was increased along with the up-regulation of p21 expression, which was ameliorated by BBR treatment. BBR downregulated the expression of REDD1 to decrease intracellular ROS content, attenuating DG-induced senescence in vitro and in vivo. Furthermore, p53 instead of HIF-1 alpha was identified as the transcriptional regulator of REDD1 in DG-induced premature senescence. Importantly, NAC and BBR reversed the expression of p53 and the content of 8-OHdG, indicating that the positive feedback loop of ROS-DNA damage response (DDR) was formed, and BBR interrupted this feedback loop to alleviate DG-induced premature senescence by reducing REDD1 expression. In addition, BBR restored DG-damaged autophagy flux by up-regulating TFEB-mediated lysosomal biosynthesis by inhibiting REDD1 expression, thereby attenuating cellular senescence.Conclusion: BBR down-regulates REDD1 expression to interrupt the ROS-DDR positive feedback loop and restore autophagic flux, thereby reducing premature senescence of RPE. Our findings elucidate the promising effects of REDD1 on cellular senescence and the great potential of BBR as a therapeutic approach.
C1 [Chen, Qingqiu; Xin, Guang; Li, Shiyi; Dong, Yuman; Yu, Xiuxian; Wan, Chengyu; Wei, Zeliang; Zhu, Yuda; Zhang, Kun; Wang, Yilan; Li, Fan; Zhang, Cuicui; Wen, E.; Li, Yulong; Niu, Hai; Huang, Wen] Sichuan Univ, West China Hosp, West China Sch Med, Lab Ethnopharmacol,Tissue orientated Property Chin, Chengdu, Sichuan, Peoples R China.
   [Huang, Wen] Keyuan Rd 4 1,Gaopeng Ave,Gaoxin Dist, Chengdu 610041, Sichuan, Peoples R China.
C3 Sichuan University
RP Huang, W (通讯作者)，Keyuan Rd 4 1,Gaopeng Ave,Gaoxin Dist, Chengdu 610041, Sichuan, Peoples R China.
EM huangwen@scu.edu.cn
RI Chen, Qingqiu/GQZ-7287-2022
FU National Natural Science Foundation of China [81973580, 81803866];
   COVID-19 Science and Technology Emergency Project of Sichuan Province of
   China [2021YFS0408]; Key Technology Research and Development Program of
   Sichuan Province of China [2022YFS0425, 2022YFS0426]; 1.3.5 Project for
   Disciplines of Excellence, West China Hospital, Sichuan University
   [ZYXY21002]; Innovative Chinese Medicine Preclinical Research Fund of
   "Liqing No. 2", West China Hospital, Sichuan University [161200012];
   Innovative Chinese Medicine and Health Products Research Academician
   Workstation of Academician Boli Zhang and Academician Beiwei Zhu, West
   China Hospital, Sichuan University [HXYS19001, HXYS19002]
FX This work was supported by the National Natural Science Foundation of
   China (81973580, 81803866); the COVID-19 Science and Technology
   Emergency Project of Sichuan Province of China (2021YFS0408), the Key
   Technology Research and Development Program of Sichuan Province of China
   (2022YFS0425, 2022YFS0426), the Innovative Chinese Medicine and Health
   Products Research Academician Workstation of Academician Boli Zhang and
   Academician Beiwei Zhu, West China Hospital, Sichuan University
   (HXYS19001, HXYS19002), the 1.3.5 Project for Disciplines of Excellence,
   West China Hospital, Sichuan University (ZYXY21002), and the Innovative
   Chinese Medicine Preclinical Research Fund of "Liqing No. 2", West China
   Hospital, Sichuan University (161200012).
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   Xu XX, 2021, AGING CELL, V20, DOI 10.1111/acel.13465
NR 30
TC 0
Z9 0
U1 14
U2 14
PU ELSEVIER GMBH
PI MUNICH
PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY
SN 0944-7113
EI 1618-095X
J9 PHYTOMEDICINE
JI Phytomedicine
PD SEP
PY 2022
VL 104
AR 154181
DI 10.1016/j.phymed.2022.154181
PG 11
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
   Medicine; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
   Medicine
GA 2Z6XA
UT WOS:000826716900003
PM 35792445
DA 2022-11-30
ER

PT J
AU Uehara, H
   Muddana, SK
   Zhang, XH
   Das, SK
   Bhuvanagiri, S
   Liu, JL
   Wu, YY
   Choi, S
   Carroll, LS
   Archer, B
   Ambati, BK
AF Uehara, Hironori
   Muddana, Santosh Kumar
   Zhang, Xiaohui
   Das, Subrata Kumar
   Bhuvanagiri, Sai
   Liu, Jinlu
   Wu, Yuanyuan
   Choi, Susie
   Carroll, Lara S.
   Archer, Bonnie
   Ambati, Balamurali K.
TI Targeted Delivery of FLT-Morpholino Using Cyclic RGD Peptide
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE cyclic RGD; morpholino oligomer; choroidal neovascularization;
   alternative splicing
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; UNITED-STATES;
   PREVALENCE; COMBRETASTATIN; RANIBIZUMAB; SUPPRESSION; INHIBITION;
   ANTAGONIST; INTEGRIN
AB Purpose: We previously showed that intravitreal injection of the sFLT morpholinooligomer (FLT-MO) suppresses laser-induced choroidal neovascularization (CNV) in mice by decreasing the membrane bound form of Flt-1 while increasing the soluble form of Flt-1 via alternative splicing shift. In this study, we examined whether cyclic RGD peptide (cRGD) can promote morpholino-oligomer accumulation in CNV following tail vein injection, and whether systemic cRGD conjugated FLT-MO (cRGD-FLT-MO) suppresses CNV growth.
   Methods: cRGD conjugated fluorescent morpholino-oligomer (cRGD-F-MO) was injected via tail vein into mice with previous retinal laser photocoagulation and examined for cRGD-F-MO accumulation in CNV. To examine whether cRGD-FLT-MO suppresses CNV growth, mice were tail-vein injected with cRGD-FLT-MO, cRGD conjugated standard morpholino-oligomer (cRGD-STD-MO), or Dulbecco's PhosphateBuffered Saline (DPBS) 1 and 4 days postlaser photocoagulation. Seven days postlaser photocoagulation, eyes were harvested and laser CNV was stained with isolectin GSIB4, allowing quantification of CNV size by confocal microscopy.
   Results: cRGD-F-MO accumulation in CNV commenced immediately after tail vein injection and could be observed even 1 day after injection. cRGD-FLT-MO tail vein injection significantly suppressed CNV size (2.7 x 10(5) +/- 0.3 x 10(5) mu m(3), P, 0.05 by Student's t-test) compared with controls (DPBS: 5.1 x 10(5) +/- 0.6 x 10(5) mu m(3) and cRGD-STD-MO: 5.5 x 10(5) +/- 0.8 x 10(5) mu m(3)).
   Conclusions: cRGD peptide facilitates morpholino-oligomer accumulation in CNV following systemic delivery. cRGD-FLT-MO suppressed CNV growth after tail-vein injection, demonstrating the potential utility of cRGD peptide for morpholinooligomer delivery to CNV.
   Translational Relevance: Current therapy for neovascular age-related macular degeneration involves intravitreal injection of anti-vascular endothelial growth factor drugs. Our results indicate that CNV can be treated systemically, thus eliminating risks and hazards associated with intravitreal injection.
C1 [Uehara, Hironori; Muddana, Santosh Kumar; Zhang, Xiaohui; Das, Subrata Kumar; Bhuvanagiri, Sai; Wu, Yuanyuan; Choi, Susie; Carroll, Lara S.; Archer, Bonnie; Ambati, Balamurali K.] Univ Utah, John A Moran Eye Ctr, Salt Lake City, UT USA.
   [Liu, Jinlu] China Med Univ, Dept Ophthalmol, Affiliated Hosp 4, Eye Hosp, Shenyang, Liaoning, Peoples R China.
C3 Utah System of Higher Education; University of Utah; China Medical
   University
RP Uehara, H (通讯作者)，Univ Utah, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM hironori.uehara@hsc.utah.edu
OI DAS, SUBRATA/0000-0001-8608-3270
FU National Institutes of Health/NEI [R01EY17950]; VA Merit Review grant
   from the US Department of Veterans Affairs Biomedical Laboratory
   Research and Development Service [BX000556]; Research to Prevent
   Blindness, Inc. (New York, NY)
FX This work was supported by the National Institutes of Health/NEI
   (R01EY17950), in part by VA Merit Review grant (BX000556) from the US
   Department of Veterans Affairs Biomedical Laboratory Research and
   Development Service and an unrestricted grant from Research to Prevent
   Blindness, Inc. (New York, NY).
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NR 24
TC 1
Z9 1
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD MAY
PY 2017
VL 6
IS 3
AR 9
DI 10.1167/tvst.6.3.9
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FH2GT
UT WOS:000410957800009
PM 28553563
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Wu, LC
   Sun, XH
   Zhou, XT
   Wen, CH
AF Wu, Liang-Cheng
   Sun, Xing-Huai
   Zhou, Xing-Tao
   Wen, Cheng-Hai
TI Unrecognized and unregistered blindness in people 70 or older in Jing'an
   district, Shanghai, China
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE blindness; unrecognized; causes
ID VISUAL IMPAIRMENT; REGISTRATION; POPULATION
AB AIM: To evaluate the efficacy of a registration system for the blind people and to monitor the blindness due to uncorrected refractive error and cataract in Jing-an district, Shanghai, China.
   METHODS: Five hundred and ten blind people, based on visual acuity screening in a population aged 70 or older were enrolled into the study. Four hundred and forty subjects were interviewed. The following data were collected on each patient: demographic data, number of hospital visits for eye related problems, distance visual acuity, visual fields, ophthalmic diagnoses, education and registration status. If the eligible subject was not registered as blind, the reason for non-registration was recorded.
   RESULTS: Ten point nine one percent blindness was due to cataract, 27.5% due to uncorrected refractive error, and only 61.59% met the eligible blindness criteria (uncorrected refractive error and cataract are not considered as eligible blindness). The first four leading causes of eligible blindness were age related macular degeneration (25.09%), myopic macular degeneration (21.40%), glaucoma (18.82%) and corneal disease (8.12%). Only 68.27% eligible blind people were registered. The patients with macular degeneration and glaucoma tended not to register. Blind people with an above primary school education were 2.59 times more likely to be registered than those who were illiterate or had only a primary school education (OR=2.59, 95%CI: 1.49-4.48, P <0.01). Patients who had 4 or more visits to the hospital requesting eye care services in a year were 2.2 times more likely to be registered than those with less than 4 visits to the hospital (OR=2.54, 95% CI: 1.47-4.38, P< 0.001). The first two leading reasons of misregistration were unknowing the registration system (48%) and unwilling to register (21%).
   CONCLUSION: Under-registration of the eligible blind people exists in the registry system. Education and the number of hospital visits for eye care services were factors associated with registration levels. Uncorrected refractive error and cataract are important causes of blindness.
C1 [Wu, Liang-Cheng; Wen, Cheng-Hai] Jingan Dist Ctr Hosp Shanghai, Dept Ophthalmol, Eye Dis Prevent & Treatment Inst Jingan Dist, Shanghai 200040, Peoples R China.
   [Sun, Xing-Huai; Zhou, Xing-Tao] Fudan Univ, Dept Ophthalmol & Vis Sci, Eye & ENT Hosp, Shanghai Med Coll, Shanghai 200031, Peoples R China.
   [Sun, Xing-Huai] Fudan Univ, State Key Lab Med Neurobiol, Inst Brain Sci, Shanghai 200031, Peoples R China.
C3 Fudan University; Fudan University
RP Wu, LC (通讯作者)，Jingan Dist Ctr Hosp Shanghai, Dept Ophthalmol, Eye Dis Prevent & Treatment Inst Jingan Dist, Shanghai 200040, Peoples R China.
EM liangchengwu@aliyun.com
RI zhou, xt/GWZ-9212-2022
FU Foundation of Health Science Research of the Health Bureau of Shanghai,
   China [2008-161]; Shi-Bai-Qian Plans of Jing'an district Health Bureau,
   Shanghai, China [2010020103]
FX Foundation items: Foundation of Health Science Research of the Health
   Bureau of Shanghai, China (No. 2008-161); Shi-Bai-Qian Plans of Jing'an
   district Health Bureau, Shanghai, China (No. 2010020103)
CR [Anonymous], OPT CORR FREEL OLD P
   [Anonymous], 2009, JING AN STAT YB 2009
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NR 19
TC 2
Z9 2
U1 0
U2 6
PU IJO PRESS
PI XI AN
PA NO 269 YOUYI EAST RD, XI AN, 710054, PEOPLES R CHINA
SN 2222-3959
EI 2227-4898
J9 INT J OPHTHALMOL-CHI
JI Int. J. Ophthalmol.
PD JUN 18
PY 2013
VL 6
IS 3
BP 321
EP 326
DI 10.3980/j.issn.2222-3959.2013.03.12
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 170DN
UT WOS:000320830300012
PM 23826526
DA 2022-11-30
ER

PT J
AU Wickremasinghe, SS
   Xie, J
   Guymer, RH
   Wong, TY
   Kawasaki, R
   Qureshi, S
AF Wickremasinghe, S. S.
   Xie, J.
   Guymer, R. H.
   Wong, T. Y.
   Kawasaki, R.
   Qureshi, S.
TI Retinal vascular changes following intravitreal ranibizumab injections
   for neovascular AMD over a 1-year period
SO EYE
LA English
DT Article
DE AMD; retinal vasculature; anti-VEGF
ID CHOROIDAL BLOOD-FLOW; MACULAR DEGENERATION; VESSEL DIAMETERS; DOSING
   REGIMEN; AGE; BEVACIZUMAB; CALIBER; RISK; VEGF; ABNORMALITIES
AB Purpose To assess retinal vascular calibre changes in eyes with neovascular age-related macular degeneration (AMD), treated with intravitreal anti-vascular endothelial growth factor agents, over a 1-year period and compare any such changes to untreated fellow eyes.
   Methods Treatment naive patients with neovascular AMD received three consecutive intravitreal injections of ranibizumab, followed by a pro re nata dosing regimen up to 1 year, with the aim of maintaining a 'fluid-free' macula. Retinal arteriolar and venular calibre was measured from digital fundus photographs at baseline and at three monthly intervals to 1 year, and summarised as central retinal artery equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively.
   Results A total of 53 injected eyes and 41 fellow, non-injected eyes were analysed. At baseline, there were no differences in retinal vascular calibre between injected and non-injected eyes (mean CRAE (SD) 144.93 (14.07) vs 145.74 (13.10) mu m, P 0.80 and mean CRVE (SD) 216.23 (25.93) vs 219.91 (22.82) mu m, P = 0.53). Over a 12-month period, retinal venular calibre dilatation occurred in injected eyes (mean CRVE change +5.71 (14.71) mu m, P = 0.007), with no change in retinal arterioles, + 0.69 (14.71) mu m, P = 0.68. In noninjected eyes, arteriolar narrowing occurred as a whole, mean CRAE change -4.20 (7.00) mu m, P = 0.001, over 12 months, with a trend for narrowing in venules, -2.16 (11.56) mu m, P = 0.28. In injected eyes, after controlling for covariates, the changes in CRVE over 12 months mirrored improvements in macular thickness, -0.06 (-0.005, -0.11) mu m, P = 0.04, and visual acuity, + 9.66 (-0.30, + 19.32) mu m, P = 0.06.
   Conclusion Intravitreal ranibizumab significantly dilated retinal venules after a 1-year period. Eye (2012) 26, 958-966; doi:10.1038/eye.2012.72; published online 4 May 2012
C1 [Wickremasinghe, S. S.; Xie, J.; Guymer, R. H.; Wong, T. Y.; Kawasaki, R.; Qureshi, S.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.
   [Wong, T. Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; National University of Singapore; Singapore
   National Eye Center
RP Wong, TY (通讯作者)，Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia.
EM twong@unimelb.edu.au
RI Kawasaki, Ryo/H-9716-2019; Wong, Tien Yin/AAC-9724-2020; Kawasaki,
   Ryo/B-7266-2009
OI Wong, Tien Yin/0000-0002-8448-1264; Kawasaki, Ryo/0000-0002-7492-6303;
   /0000-0001-6694-3587; Guymer, Robyn/0000-0002-9441-4356
FU National Health and Medical Research Council [52993]; Novartis; Pfizer
FX This study was partially funded by a National Health and Medical
   Research Council grant, 52993. Drs Guymer and Wong are on advisory
   boards of Novartis and Pfizer and have received research funding,
   speaking fees, travel and accommodation from either/both companies. The
   Centre for Eye Research Australia receives Operational Infrastructure
   Support from the Victorian Government. This study was approved by the
   Human Research and Ethics Committee of the Royal Victorian Eye and Ear
   Hospital (RVEEH).
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NR 38
TC 8
Z9 8
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD JUL
PY 2012
VL 26
IS 7
BP 958
EP 966
DI 10.1038/eye.2012.72
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 973LE
UT WOS:000306360800009
PM 22562186
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Rosen, RB
   Hu, DN
   Chen, M
   McCormick, SA
   Walsh, J
   Roberts, JE
AF Rosen, Richard B.
   Hu, Dan-Ning
   Chen, Min
   McCormick, Steven A.
   Walsh, Joseph
   Roberts, Joan E.
TI Effects of melatonin and its receptor antagonist on retinal pigment
   epithelial cells against hydrogen peroxide damage
SO MOLECULAR VISION
LA English
DT Article
ID OXIDATIVE STRESS; MACULAR DEGENERATION; IN-VITRO; GLUTAMATE
   EXCITOTOXICITY; LIPID-PEROXIDATION; UVEAL MELANOCYTES; PATHWAYS;
   ANTIOXIDANTS; EXPRESSION; APOPTOSIS
AB Purpose: Recently, we reported finding that circulating melatonin levels in age-related macular degeneration patients were significantly lower than those in age-matched controls. The purpose of this study was to investigate the hypothesis that melatonin deficiency may play a role in the oxidative damage of the retinal pigment epithelium (RPE) by testing the protective effect of melatonin and its receptor antagonist on RPE cells exposed to H2O2 damage.
   Methods: Cultured human RPE cells were subjected to oxidative stress induced by 0.5 mM H2O2. Cell viability was measured using the microculture tetrazoline test (MTT) assay. Cells were pretreated with or without melatonin for 24 h. Luzindole (50 mu M), a melatonin membrane-receptor antagonist, was added to the culture 1 h before melatonin to distinguish direct antioxidant effects from indirect receptor-dependent effects. All tests were performed in triplicate.
   Results: H2O2 at 0.5 mM decreased cell viability to 20% of control levels. Melatonin showed dose-dependent protective effects on RPE cells against H2O2. Cell viability of RPE cells pretreated with 10(-10), 10(-8), 10(-6), and 10(-4) M melatonin for 24 h was 130%, 160%, 187%, and 230% of cells treated with H2O2 alone (all p<0.05). Using cells cultured without H2O2 as the control, cell viability of cells treated with H2O2 after pretreatment with 10(-10)-10(-4) M melatonin was still significantly lower than that of the controls, suggesting that melatonin significantly decreased but did not completely abolish the in vitro cytotoxic effects of H2O2. Luzindole completely blocked melatonin's protective effects at low concentrations of melatonin (10(-10)-10(-8) M) but not at high concentrations (10(-6)-10(-4) M).
   Conclusions: Melatonin has a partial protective effect on RPE cells against H2O2 damage across a wide range of concentrations (10(-10)-10(-4) M). This protective effect occurs through the activation of melatonin membrane receptors at low concentrations (10(-10)-10(-8) M) and through both the direct antioxidant and indirect receptor activation effects at high concentrations (10(-6)-10(-4) M).
C1 [Roberts, Joan E.] Fordham Univ, Div Nat Sci, New York, NY 10023 USA.
   [Rosen, Richard B.; Hu, Dan-Ning; McCormick, Steven A.; Walsh, Joseph] New York Med Coll, New York Eye & Ear Infirm, Dept Ophthalmol, New York, NY USA.
   [Hu, Dan-Ning; Chen, Min; McCormick, Steven A.] New York Med Coll, New York Eye & Ear Infirm, Dept Pathol & Lab Med, Tissue Culture Ctr, New York, NY USA.
C3 Fordham University; New York Eye & Ear Infirmary of Mount Sinai; New
   York Medical College; New York Eye & Ear Infirmary of Mount Sinai; New
   York Medical College
RP Roberts, JE (通讯作者)，Fordham Univ, Div Nat Sci, 113 W 60th St, New York, NY 10023 USA.
EM jroberts@fordham.edu
FU Bendheim-Lowenstein Family Foundation; New York Eye and Ear Infirmary
   Pathology Research Fund, New York, NY
FX This work was supported by the Bendheim-Lowenstein Family Foundation and
   New York Eye and Ear Infirmary Pathology Research Fund, New York, NY.
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NR 57
TC 41
Z9 43
U1 0
U2 0
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUN 20
PY 2012
VL 18
IS 169-73
BP 1640
EP 1648
PG 9
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 962OW
UT WOS:000305555700001
PM 22773902
DA 2022-11-30
ER

PT J
AU Reeves, BC
   Langham, J
   Walker, J
   Grieve, R
   Chakravarthy, U
   Tomlin, K
   Carpenter, J
   Guerriero, C
   Harding, SP
AF Reeves, Barnaby C.
   Langham, Julia
   Walker, Jemma
   Grieve, Richard
   Chakravarthy, Usha
   Tomlin, Keith
   Carpenter, James
   Guerriero, Carla
   Harding, Simon P.
CA Verteporfin Photodynamic Therapy
TI Verteporfin Photodynamic Therapy Cohort Study Report 2: Clinical
   Measures of Vision and Health-Related Quality of Life
SO OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; COST-EFFECTIVENESS; UTILITY; RANIBIZUMAB; OUTCOMES
AB Purpose: To quantify decreases in health-related quality of life (HRQoL) for given deterioration in clinical measures of vision; to describe the shape of these relationships; and to test whether the gradients of these relationships change with duration of visual loss.
   Design: A prospective, longitudinal study of patients treated with verteporfin photodynamic therapy in the United Kingdom National Health Service.
   Participants: Patients with neovascular age-related macular degeneration (AMD) treated in 18 ophthalmology departments in the United Kingdom with expertise in management of neovascular AMD.
   Methods: Responses to HRQoL questionnaires (Short Form 36 [SF-36] and National Eye Institute Visual Functioning Questionnaire [NEIVFQ]) and clinical measures of vision were recorded at baseline and at follow-up visits. Mixed regression models were used to characterize the relationships of interest.
   Main Outcome Measures: Measures of vision were best-corrected visual acuity (BCVA) and contrast sensitivity (CS). The SF-36 physical and mental component scores (PCS and MCS), SF-6D utility, and distance, near, and composite NEIVFQ scores were derived to characterize HRQoL.
   Results: The SF-6D, PCS, and MCS were linearly associated with BCVA; predicted decreases for a 5-letter drop in BCVA in the better-seeing eye were 0.0058, 0.245, and 0.546, respectively (all P<0.0001). Gradients were not influenced by duration of follow-up. Models predicting distance, near, and composite NEIVFQ scores from BCVA were quadratic; predicted decreases for a 5-letter drop in BCVA in the better-seeing eye were 5.08, 5.48, and 3.90, respectively (all P<0.0001). The BCVA predicted HRQoL scores more strongly than CS.
   Conclusions: Clinically significant deterioration in clinical measures of vision is associated with small decreases in generic and vision-specific HRQoL. Our findings are important for further research modeling the cost effectiveness of current and future interventions for neovascular AMD.
   Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2009; 116:2463-2470 (C) 2009 by the American Academy of Ophthalmology.
C1 [Harding, Simon P.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England.
   [Reeves, Barnaby C.; Langham, Julia; Walker, Jemma; Grieve, Richard; Tomlin, Keith; Carpenter, James; Guerriero, Carla] London Sch Hyg & Trop Med, London WC1, England.
   [Chakravarthy, Usha] Queens Univ Belfast, Belfast, Antrim, North Ireland.
C3 Royal Liverpool & Broadgreen University Hospitals NHS Trust; Royal
   Liverpool University Hospital; University of Liverpool; University of
   London; London School of Hygiene & Tropical Medicine; Queens University
   Belfast
RP Reeves, BC (通讯作者)，Univ Bristol, Bristol Royal Infirm, Clin Trials & Evaluat Unit, Level 7,Queens Bldg, Bristol BS2 8HW, Avon, England.
OI Chakravarthy, Usha/0000-0002-2606-3734; Carpenter,
   James/0000-0003-3890-6206; Harding, Simon/0000-0003-4676-1158; Grieve,
   Richard/0000-0001-8899-1301
FU United Kingdom National Institute for Health Research; Health Technology
   Assessment Programme, Southampton. England
FX Supported by The United Kingdom National Institute for Health Research,
   Health Technology Assessment Programme, Southampton. England. The views
   and opinions expressed are those of the authors and do not necessarily
   reflect those of the Department of Health.
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NR 33
TC 9
Z9 9
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD DEC
PY 2009
VL 116
IS 12
BP 2463
EP 2470
DI 10.1016/j.ophtha.2009.10.031
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 530HE
UT WOS:000272579200030
PM 19948277
DA 2022-11-30
ER

PT J
AU Bachmann, BC
   Bachofner, M
   Mickan, S
   Stojcic, D
   Carnier, KA
   Giamboni, A
   Neugebauer, Z
   Lienhard, KR
   Bachmann, LM
AF Bachmann, Barbara Claudia
   Bachofner, Marilena
   Mickan, Sandra
   Stojcic, Danica
   Carnier, Kerstin A.
   Giamboni, Alessia
   Neugebauer, Zuzana
   Lienhard, Kenny R.
   Bachmann, Lucas M.
TI Frequency of Eye Diseases in Residents of Nursing Homes-1-Year Results
   of a Novel Telemedicine Service in Switzerland
SO KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE
LA English
DT Article
DE telemedicine; geriatric ophthalmology; health service research
ID PREVALENCE; HOME
AB Purpose For the elderly in nursery homes, a visit to the ophthalmologist is a burden, which might lead to undertreatment. We have recently started offering a novel ophthalmological service combining onsite examination and telemedical interpretation for patients with limited access to ophthalmological care. This study summarises the frequency of findings of treatable eye diseases after the first year of operation in participants who dropped out from regular ophthalmological control. Methods Participants' clinical characteristics, frequency of service utilisation, and findings were extracted from the system and analysed. Results Of 1946 residents approached, 540 (27.7%; 1080 eyes) signed up for the service. A complete examination was possible in 412 persons (813 eyes) and partially possible in the remaining 128. The mean age of the examined participants mean age was 83.9 years (SD 9.7), and they were predominantly female (69.8%). The majority had a diagnosis of dementia (54.5%) and 20.2% had diabetes mellitus requiring treatment. The median care level (ranging from 0 - 12) was 7 (interquartile range 6 - 9), corresponding to a care need of 121 - 140 min/d. The mean best-corrected decimal visual acuity was 0.55 (SD 0.24). For 164 eyes (15.2%), the current spectacle correction was insufficient. An untreated cataract was present in 145 eyes (13.4%), 89 eyes (8.2%) were receiving glaucoma treatment, and 7 eyes had a decompensated glaucoma. Dry age-related macular degeneration (AMD) appeared in 276 eyes (25.6%), 12 eyes (1.1%) had wet AMD, and 24 eyes (11.0%) among patients with diabetes showed signs of diabetic retinopathy. Other pathologies were uncommon. Conclusion Residents of nursery homes, who are unable to attend regular ophthalmological control, show various treatable ophthalmological conditions, including cataracts, glaucoma, and retinal pathologies. Screening with a novel telemedicine service allows for the identification of treatable conditions and careful planning and referral of patients to appropriate clinics having the necessary infrastructure for this particular population.
C1 [Bachmann, Barbara Claudia; Bachofner, Marilena; Mickan, Sandra; Stojcic, Danica; Carnier, Kerstin A.; Giamboni, Alessia; Neugebauer, Zuzana; Lienhard, Kenny R.; Bachmann, Lucas M.] Mobile Messungen Augenmobil AG, Verena Conzett Str 9, CH-8004 Zurich, Switzerland.
RP Bachmann, BC (通讯作者)，Mobile Messungen Augenmobil AG, Verena Conzett Str 9, CH-8004 Zurich, Switzerland.
EM bachmann@augenmobil.ch
CR Arruabarrena C, 2021, J CLIN MED, V10, DOI 10.3390/jcm10153281
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NR 20
TC 0
Z9 0
U1 2
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0023-2165
EI 1439-3999
J9 KLIN MONATSBL AUGENH
JI Klinische Monatsblat. Augenheilkunde
PD APR
PY 2022
VL 239
IS 04
BP 610
EP 614
DI 10.1055/a-1778-4782
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 0U1CA
UT WOS:000787394100058
PM 35472817
DA 2022-11-30
ER

PT J
AU Koster, C
   van den Hurk, KT
   ten Brink, JB
   Lewallen, CF
   Stanzel, BV
   Bharti, K
   Bergen, AA
AF Koster, Celine
   van den Hurk, Koen T.
   ten Brink, Jacoline B.
   Lewallen, Colby F.
   Stanzel, Boris, V
   Bharti, Kapil
   Bergen, Arthur A.
TI Sodium-Iodate Injection Can Replicate Retinal Degenerative Disease
   Stages in Pigmented Mice and Rats: Non-Invasive Follow-Up Using OCT and
   ERG
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE retinal degeneration; retinal pigment epithelium; sodium iodate; mouse;
   rat; C57BL; 6J; Brown Norway; rodent; OCT; ERG; macula degeneration
ID EPITHELIUM DIFFUSION BARRIER; MACULAR DEGENERATION; OXIDATIVE STRESS;
   ANIMAL-MODELS; RPE CELLS; AGE; MOUSE; MECHANISMS; DAMAGE; SUSCEPTIBILITY
AB Purpose: The lack of suitable animal models for (dry) age-related macular degeneration (AMD) has hampered therapeutic research into the disease, so far. In this study, pigmented rats and mice were systematically injected with various doses of sodium iodate (SI). After injection, the retinal structure and visual function were non-invasively characterized over time to obtain in-depth data on the suitability of these models for studying experimental therapies for retinal degenerative diseases, such as dry AMD. Methods: SI was injected into the tail vein (i.v.) using a series of doses (0-70 mg/kg) in adolescent C57BL/6J mice and Brown Norway rats. The retinal structure and function were assessed non-invasively at baseline (day 1) and at several time points (1-3, 5, and 10-weeks) post-injection by scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and electroretinography (ERG). Results: After the SI injection, retinal degeneration in mice and rats yielded similar results. The lowest dose (10 mg/kg) resulted in non-detectable structural or functional effects. An injection with 20 mg/kg SI did not result in an evident retinal degeneration as judged from the OCT data. In contrast, the ERG responses were temporarily decreased but returned to baseline within two-weeks. Higher doses (30, 40, 50, and 70 mg/kg) resulted in moderate to severe structural RPE and retinal injury and decreased the ERG amplitudes, indicating visual impairment in both mice and rat strains. Conclusions: After the SI injections, we observed dose-dependent structural and functional pathological effects on the retinal pigment epithelium (RPE) and retina in the pigmented mouse and rat strains that were used in this study. Similar effects were observed in both species. In particular, a dose of 30 mg/kg seems to be suitable for future studies on developing experimental therapies. These relatively easily induced non-inherited models may serve as useful tools for evaluating novel therapies for RPE-related retinal degenerations, such as AMD.
C1 [Koster, Celine; van den Hurk, Koen T.; ten Brink, Jacoline B.; Bergen, Arthur A.] Univ Amsterdam, Amsterdam Univ Med Ctr AUMC, Dept Human Genet, Sect Ophthalmogenet,Locat AMC, NL-1105 AZ Amsterdam, Netherlands.
   [Lewallen, Colby F.] Georgia Inst Technol, GW Woodruff Sch Mech Engn, Atlanta, GA 30332 USA.
   [Stanzel, Boris, V] Knappschaft Hosp Saar, Eye Clin Sulzbach, D-66280 Sulzbach, Germany.
   [Stanzel, Boris, V] Univ Bonn, Dept Ophthalmol, D-53113 Bonn, Germany.
   [Bharti, Kapil] NEI, Ocular & Stem Cell Res Sect, NIH, Bethesda, MD 20892 USA.
   [Bergen, Arthur A.] UvA, Meibergdreef, Locat AMC, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands.
C3 University of Amsterdam; University System of Georgia; Georgia Institute
   of Technology; University of Bonn; National Institutes of Health (NIH) -
   USA; NIH National Eye Institute (NEI); University of Amsterdam
RP Bergen, AA (通讯作者)，Univ Amsterdam, Amsterdam Univ Med Ctr AUMC, Dept Human Genet, Sect Ophthalmogenet,Locat AMC, NL-1105 AZ Amsterdam, Netherlands.; Bergen, AA (通讯作者)，UvA, Meibergdreef, Locat AMC, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands.
EM c.koster@amsterdamumc.nl; k.t.vandenhurk@amsterdamumc.nl;
   j.b.tenbrink@amsterdamumc.nl; colby.lewallen@gatech.edu;
   boris.stanzel@kksaar.de; kapil.bharti@nih.gov; aabergen@amsterdamumc.nl
OI ten Brink, Jacoline B/0000-0001-7884-0067; Koster,
   Celine/0000-0002-0936-3970
FU Stichting Uitzicht [UZ 2016-21]; Rotterdamse Stichting Blindenbelangen
   [B20160043]; Stichting Lijf en Leven [42]; TKI-PPP Health Holland-Biogen
   Consortium [2020-1935]; Stichting Blindenhulp; Stichting voor
   Ooglijders; Stichting Uitzicht (Stichting MD Nederland); Stichting
   Uitzicht (Landelijke Stichting voor Blinden en Slechtzienden); Stichting
   Uitzicht (Stichting Retina Fonds Nederland); Stichting Uitzicht
   (Oogfonds)
FX This project was (in part) funded by the following grants: Stichting
   Uitzicht (UZ 2016-21) including the Stichting MD Nederland, Landelijke
   Stichting voor Blinden en Slechtzienden, Stichting Retina Fonds
   Nederland, Oogfonds), the Rotterdamse Stichting Blindenbelangen
   (#B20160043), Stichting Blindenhulp, Stichting voor Ooglijders and
   Stichting Lijf en Leven (#42), and TKI-PPP Health Holland-Biogen
   Consortium (2020-1935) (all to A.A.B).
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NR 105
TC 0
Z9 0
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD MAR
PY 2022
VL 23
IS 6
AR 2918
DI 10.3390/ijms23062918
PG 21
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 0C4YO
UT WOS:000775320800001
PM 35328338
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Schnabel, B
   Kuhrt, H
   Wiedemann, P
   Bringmann, A
   Hollborn, M
AF Schnabel, Benjamin
   Kuhrt, Heidrun
   Wiedemann, Peter
   Bringmann, Andreas
   Hollborn, Margrit
TI Osmotic regulation of aquaporin-8 expression in retinal pigment
   epithelial cells in vitro: Dependence on K-ATP channel activation
SO MOLECULAR VISION
LA English
DT Article
ID SENSITIVE POTASSIUM CHANNELS; NONSELECTIVE CATION CHANNEL;
   SMALL-MOLECULE INHIBITOR; DIABETIC-RETINOPATHY; REACTIVE ASTROCYTES;
   HYDROGEN-PEROXIDE; PLASMA-MEMBRANE; BLOOD-PRESSURE; RISK-FACTORS; GROWTH
AB Purpose: The expression of aquaporin-8 (AQP8), which plays a crucial role in the maintenance of the cellular fluid and electrolyte balance, was shown to be increased in RPE cells under hyperosmotic conditions. The aim of the present study was to investigate the mechanisms of hyperosmotic AQP8 gene expression and the localization of AQP8 in cultured human RPE cells.
   Methods: Hyperosmolarity was produced with the addition of 100 mM NaCl or 200 mM sucrose. Hypoxia was induced by cell culture in a 0.2% O-2 atmosphere or the addition of the hypoxia mimetic CoCl2. Oxidative stress was induced by the addition of H2O2. Gene expression was determined with real-time RT-PCR analysis. AQP8 protein localization and secretion of VEGF were evaluated with immunocytochemistry, western blotting, and enzyme-linked immunosorbent assay (ELISA).
   Results: Immunocytochemical and western blot data suggest that the AQP8 protein is mainly located in the mitochondria. Extracellular hyperosmolarity, hypoxia, and oxidative stress induced increases in AQP8 gene expression. Hyperosmotic AQP8 gene expression was reduced by inhibitors of the p38 MAPK and PI3K signal transduction pathways, and by JAK(2) and PLA(2) inhibitors, and was in part mediated by the transcriptional activity of CREB. Hyperosmotic AQP8 gene expression was also reduced by autocrine/paracrine interleukin-1 signaling, the sulfonylureas glibenclamide and glipizide, which are known inhibitors of K-ATP channel activation, and a pannexin-blocking peptide. The K-ATP channel opener pinacidil increased the expression of AQP8 under control conditions. The cells contained Kir6.1 and SUR2B gene transcripts and displayed Kir6.1 immunoreactivity. siRNA-mediated knockdown of AQP8 caused increases in hypoxic VEGF gene expression and secretion and decreased cell viability under control, hyperosmotic, and hypoxic conditions.
   Conclusions: The data indicate that hyperosmotic expression of AQP8 in RPE cells is dependent on the activation of K-ATP channels. The data suggest that AQP8 activity decreases the hypoxic VEGF expression and improves the viability of RPE cells which may have impact for ischemic retinal diseases like diabetic retinopathy and age-related macular degeneration.
C1 [Schnabel, Benjamin; Wiedemann, Peter; Bringmann, Andreas; Hollborn, Margrit] Univ Leipzig, Dept Ophthalmol, Leipzig, Germany.
   [Schnabel, Benjamin; Wiedemann, Peter; Bringmann, Andreas; Hollborn, Margrit] Univ Leipzig, Eye Hosp, Leipzig, Germany.
   [Kuhrt, Heidrun] Univ Leipzig, Med Fac, Inst Anat, Leipzig, Germany.
C3 Leipzig University; Leipzig University; Leipzig University
RP Hollborn, M (通讯作者)，Univ Leipzig, Fac Med, Dept Ophthalmol, Liebigstr 10-14, D-04103 Leipzig, Germany.; Hollborn, M (通讯作者)，Univ Leipzig, Fac Med, Eye Hosp, Liebigstr 10-14, D-04103 Leipzig, Germany.
EM hollbm@medizin.uni-leipzig.de
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NR 85
TC 2
Z9 2
U1 0
U2 2
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD DEC 30
PY 2020
VL 26
BP 797
EP 817
PG 21
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA PR3BW
UT WOS:000607115500001
PM 33456300
DA 2022-11-30
ER

PT J
AU Biswal, MR
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   Dorey, CK
   Lewin, AS
AF Biswal, Manas R.
   Justis, Bradley D.
   Han, Pingyang
   Li, Hong
   Gierhart, Dennis
   Dorey, Cheryl K.
   Lewin, Alfred S.
TI Daily zeaxanthin supplementation prevents atrophy of the retinal pigment
   epithelium (RPE) in a mouse model of mitochondrial oxidative stress
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; CHOROIDAL NEOVASCULARIZATION;
   BETA-CAROTENE; RAT MODEL; HUMAN EYE; AGE; LUTEIN; CELLS; ACCUMULATION
AB Oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD). The dry form of AMD (geographic atrophy) is characterized by loss of RPE, photoreceptors, and macular pigments. The cumulative effects of oxidative stress impact mitochondrial function in RPE. In Sod2(flox/flox)VMD2-cre mice, the RPE specific deletion of Sod2, the gene for mitochondrial manganese superoxide dismutase (MnSOD), leads to elevated oxidative stress in retina and RPE, and causes changes in the RPE and underlying Bruch's membrane that share some features of AMD. This study tested the hypothesis that zeaxanthin supplementation would reduce oxidative stress and preserve RPE structure and function in these mice. Zeaxanthin in retina/RPE/choroid and liver was quantified by LC/MS, retinal function and structure were evaluated by electroretinogram (ERG) and spectral domain optical coherence tomography (SD-OCT), and antioxidant gene expression was measured by RT-PCR. After one month of supplementation, zeaxanthin levels were 5-fold higher in the retina/RPE/choroid and 12-fold higher in liver than in unsupplemented control mice. After four months of supplementation, amplitudes of the ERG a-wave (function of rod photoreceptors) and b-wave (function of the inner retina) were not different in supplemented and control mice. In contrast, the c-wave amplitude (a measure of RPE function) was 28% higher in supplemented mice than in control mice. Higher RPE/choroid expression of antioxidant genes (Cat, Gstm1, Hmox1, Nqo1) and scaffolding protein Sqstm1 were found in supplemented mice than in unsupplemented controls. Reduced nitrotyrosine content in the RPE/choroid was demonstrated by ELISA. Preliminary assessment of retinal ultrastructure indicated that supplementation supported better preservation of RPE structure with more compact basal infoldings and intact mitochondria. We conclude that daily zeaxanthin supplementation protected RPE cells from mitochondrial oxidative stress associated with deficiency in the MnSOD and thereby improved RPE function early in the disease course.
C1 [Biswal, Manas R.; Justis, Bradley D.; Han, Pingyang; Li, Hong; Lewin, Alfred S.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32611 USA.
   [Biswal, Manas R.; Lewin, Alfred S.] Univ Florida, Ctr Vis Res, Gainesville, FL 32611 USA.
   [Biswal, Manas R.] Univ S Florida, Coll Pharm, Tampa, FL 33620 USA.
   [Gierhart, Dennis] ZeaVision, Chesterfield, MO USA.
   [Dorey, Cheryl K.] Virginia Tech Carilion Sch Med, Roanoke, VA USA.
   [Lewin, Alfred S.] Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA.
C3 State University System of Florida; University of Florida; State
   University System of Florida; University of Florida; State University
   System of Florida; University of South Florida; State University System
   of Florida; University of Florida
RP Biswal, MR (通讯作者)，Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32611 USA.; Biswal, MR (通讯作者)，Univ Florida, Ctr Vis Res, Gainesville, FL 32611 USA.; Biswal, MR (通讯作者)，Univ S Florida, Coll Pharm, Tampa, FL 33620 USA.
EM biswal@ufl.edu
OI Biswal, Manas/0000-0002-9685-2923; Lewin, Alfred/0000-0002-4192-9727
FU National Eye Institute (NEI) [R01EY020825, R01EY026268, 1K99EY027013];
   NEI core grant [P30 EY02172]; ZeaVision LLC; Bright Focus Foundation;
   Shaler Richardson Professorship endowment; NATIONAL EYE INSTITUTE
   [R01EY026268] Funding Source: NIH RePORTER
FX This research was supported by grants from the National Eye Institute
   (NEI) (R01EY020825 [ASL]; R01EY026268 [ASL]; 1K99EY027013 [MRB]), an NEI
   core grant to the University of Florida (P30 EY02172 [ASL]), a pilot
   grant from ZeaVision LLC (MRB), a grant from Bright Focus Foundation
   (ASL & MRB) and the Shaler Richardson Professorship endowment (ASL).
   None of the funding organization had any role in the design, data
   collection, analysis or preparation of the manuscript for publication.
   The funder provided support in the form of salaries for authors [MRB,
   ASL, HL, PH] and resources for research, but did not have any additional
   role in the study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
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NR 51
TC 23
Z9 23
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 28
PY 2018
VL 13
IS 9
AR e0203816
DI 10.1371/journal.pone.0203816
PG 16
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GV3OT
UT WOS:000446005500010
PM 30265681
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Guo, JH
   Hong, L
   West, XZ
   Wang, H
   Salomon, RG
AF Guo, Junhong
   Hong, Li
   West, Xiaoxia Z.
   Wang, Hua
   Salomon, Robert G.
TI Bioactive 4-Oxoheptanedioic Monoamide Derivatives of Proteins and
   Ethanolaminephospholipids: Products of Docosahexaenoate Oxidation
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID LIPID-PEROXIDATION; OXIDIZED PHOSPHOLIPIDS; ADDUCTS; IDENTIFICATION;
   PROTEASOME; GENERATION; ISOKETALS; PLASMA; FAMILY; TLR2
AB Oxidative stress causes lipid-derived oxidative modification of biomolecules that has been implicated in many pathological states. Phospholipids containing polyunsaturated fatty acids are major targets of free radical-initiated oxidation. Phospholipids that incorporate docosahexaenoate (DHA) are highly enriched in important neural structures including the brain and retina, where DHA comprises 40% and 60% of total fatty acids, respectively. Oxidative fragmentation of 2-docosahexaenoyl-1-palmityl-sn-glycerophosphocholine generates esters of 4-hydroxy-7-oxohept-5-enoic acid (HOHA) and 4-keto-7-oxohept-5-enoic acid (KOHA) with 2-lysophosphatidylcholine, HOHA-PC, and KOHA-PC. Covalent HOHA adducts that incorporate the primary amino groups of proteins and ethanolamine phospholipids in carboxyethylpyrrole (CEP) derivatives were detected immunologically with anti-CEP antibodies in human tumors, retina, and blood. Now, we generated an anti-OHdiA antibody to test the hypothesis that KOHA adducts, which incorporate the primary amino groups of proteins or ethanolamine phospholipids in 4-oxo-heptanedioic (OHdiA) monoamide derivatives, are present in vivo. However, whereas the anti-CEP antibody is highly specific and does not cross-react with the OHdiA monoamide epitope, the anti-OHdiA monoamide antibody cross-reacted with CEP epitopes making it of little value as an analytical tool for OHdiA monoamides but suggesting the possibility that OHdiA monoamides would exhibit receptor-mediated biological activity similar to that of CEP. An LC-MS/MS method was developed that allows quantification of OHdiA derivatives in biological samples. We now find that KOHA-PC forms OHdiA monoamide adducts of proteins and ethanolamine phospholipids and that OHdiA-protein levels are significantly higher than OHdiA-ethanloamine phospholipid levels in blood from healthy human subjects, 0.45 mu M and 0.18 mu M, respectively (n = 3, and p = 0.027). OHdiA monoamide epitopes are angiogenic, causing TLR2-dependent adhesion and tube formation by human umbilical vein endothelial cells. OHdiA monoamide epitopes are only slightly less potent than CEP epitopes that contribute to the pathological angiogenesis of age-related macular degeneration and tumor growth.
C1 [Guo, Junhong; Hong, Li; Wang, Hua; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, 2074 Adelbert Rd, Cleveland, OH 44106 USA.
   [West, Xiaoxia Z.] Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44195 USA.
C3 Case Western Reserve University; Cleveland Clinic Foundation
RP Salomon, RG (通讯作者)，Case Western Reserve Univ, Dept Chem, 2074 Adelbert Rd, Cleveland, OH 44106 USA.
EM rgs@case.edu
RI Guo, Junhong/O-6316-2017
OI Guo, Junhong/0000-0003-0005-4837; Salomon, Robert/0000-0001-9456-3557
FU NIH [EY016813, GM021249]; NATIONAL EYE INSTITUTE [P30EY011373,
   R01EY016813] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL
   MEDICAL SCIENCES [R01GM021249] Funding Source: NIH RePORTER
FX This work was supported by NIH Grants EY016813 and GM021249 to R.G.S.
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NR 32
TC 1
Z9 1
U1 0
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
EI 1520-5010
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD OCT
PY 2016
VL 29
IS 10
BP 1706
EP 1719
DI 10.1021/acs.chemrestox.6b00218
PG 14
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA DZ3YK
UT WOS:000385785600013
PM 27618287
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Chen, Q
   Leng, T
   Zheng, LL
   Kutzscher, L
   Ma, J
   de Sisternes, L
   Rubin, DL
AF Chen, Qiang
   Leng, Theodore
   Zheng, Luoluo
   Kutzscher, Lauren
   Ma, Jeffrey
   de Sisternes, Luis
   Rubin, Daniel L.
TI Automated drusen segmentation and quantification in SD-OCT images
SO MEDICAL IMAGE ANALYSIS
LA English
DT Article
DE Drusen segmentation; SD-OCT; Projection image; Retinal pigment
   epithelium; AMD
ID OPTICAL COHERENCE TOMOGRAPHY; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; VISUALIZATION; ALGORITHM; PATHOLOGY; FILTER
AB Spectral domain optical coherence tomography (SD-OCT) is a useful tool for the visualization of drusen, a retinal abnormality seen in patients with age-related macular degeneration (AMD); however, objective assessment of drusen is thwarted by the lack of a method to robustly quantify these lesions on serial OCT images. Here, we describe an automatic drusen segmentation method for SD-OCT retinal images, which leverages a priori knowledge of normal retinal morphology and anatomical features. The highly reflective and locally connected pixels located below the retinal nerve fiber layer (RNFL) are used to generate a segmentation of the retinal pigment epithelium (RPE) layer. The observed and expected contours of the RPE layer are obtained by interpolating and fitting the shape of the segmented RPE layer, respectively. The areas located between the interpolated and fitted RPE shapes (which have nonzero area when drusen occurs) are marked as drusen. To enhance drusen quantification, we also developed a novel method of retinal projection to generate an en face retinal image based on the RPE extraction, which improves the quality of drusen visualization over the current approach to producing retinal projections from SD-OCT images based on a summed-voxel projection (SVP), and it provides a means of obtaining quantitative features of drusen in the en face projection. Visualization of the segmented drusen is refined through several post-processing steps, drusen detection to eliminate false positive detections on consecutive slices, drusen refinement on a projection view of drusen, and drusen smoothing. Experimental evaluation results demonstrate that our method is effective for drusen segmentation. In a preliminary analysis of the potential clinical utility of our methods, quantitative drusen measurements, such as area and volume, can be correlated with the drusen progression in non-exudative AMD, suggesting that our approach may produce useful quantitative imaging biomarkers to follow this disease and predict patient outcome. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Chen, Qiang; de Sisternes, Luis; Rubin, Daniel L.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA.
   [Chen, Qiang] Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Nanjing 210094, Jiangsu, Peoples R China.
   [Leng, Theodore; Zheng, Luoluo; Kutzscher, Lauren; Ma, Jeffrey] Stanford Univ, Sch Med, Byers Eye Inst Stanford, Palo Alto, CA 94303 USA.
   [Rubin, Daniel L.] Stanford Univ, Dept Med Biomed Informat, Stanford, CA 94305 USA.
C3 Stanford University; Nanjing University of Science & Technology;
   Stanford University; Stanford University
RP Chen, Q (通讯作者)，Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Nanjing 210094, Jiangsu, Peoples R China.
EM chen2qiang@163.com; dlrubin@stanford.edu
RI Leng, Theodore/AAQ-7459-2020; chen, qiang/GWZ-7308-2022
OI Leng, Theodore/0000-0002-8461-3562
FU Bio-X Interdisciplinary Initiatives Program of Stanford University;
   National Cancer Institute, National Institutes of Health
   [U01-CA-142555]; National Natural Science Foundations of China
   [60805003]; Programme of Introducing Talents of Discipline to
   Universities [B13022]; NATIONAL CANCER INSTITUTE [U01CA142555] Funding
   Source: NIH RePORTER
FX The authors sincerely thank Noy Cohen and Audrey K Ellerbee for their
   valuable input into this work, and thank Jarrett Rosenberg for the
   statistic analysis of drusen segmentation results. This work was
   supported by a grant from the Bio-X Interdisciplinary Initiatives
   Program of Stanford University, a grant from the National Cancer
   Institute, National Institutes of Health, Grant No. U01-CA-142555, and
   grants from the National Natural Science Foundations of China under
   Grant No. 60805003, Qing Lan Project, and the Programme of Introducing
   Talents of Discipline to Universities, Grant No. B13022.
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NR 42
TC 80
Z9 89
U1 0
U2 49
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 1361-8415
EI 1361-8423
J9 MED IMAGE ANAL
JI Med. Image Anal.
PD DEC
PY 2013
VL 17
IS 8
BP 1058
EP 1072
DI 10.1016/j.media.2013.06.003
PG 15
WC Computer Science, Artificial Intelligence; Computer Science,
   Interdisciplinary Applications; Engineering, Biomedical; Radiology,
   Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical
   Imaging
GA 247YX
UT WOS:000326662000014
PM 23880375
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Fleckenstein, M
   Schmitz-Valckenberg, S
   Adrion, C
   Visvalingam, S
   Gobel, AP
   Mossner, A
   von Strachwitz, CN
   Mackensen, F
   Pauleikhoff, D
   Wolf, S
   Mansmann, U
   Holz, FG
AF Fleckenstein, Monika
   Schmitz-Valckenberg, Steffen
   Adrion, Christine
   Visvalingam, Sivatharisini
   Goebel, Arno P.
   Moessner, Andreas
   von Strachwitz, Claudia N.
   Mackensen, Friederike
   Pauleikhoff, Daniel
   Wolf, Sebastian
   Mansmann, Ulrich
   Holz, Frank G.
CA FAM Study Grp
TI Progression of Age-Related Geographic Atrophy: Role of the Fellow Eye
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID FUNDUS AUTOFLUORESCENCE PATTERNS; SCANNING LASER OPHTHALMOSCOPY; MACULAR
   DEGENERATION; DISEASE PROGRESSION; NATURAL-HISTORY; CHOROIDAL
   NEOVASCULARIZATION; JUNCTIONAL ZONE; CLINICAL-TRIALS; AMD; MACULOPATHY
AB PURPOSE. To evaluate the role of fellow eye status in determining progression of geographic atrophy (GA) in patients with age-related macular degeneration (AMD).
   METHODS. A total of 300 eyes with GA of 193 patients from the prospective, longitudinal, natural history FAM Study were classified into three groups according to the AMD manifestation in the fellow eye at baseline examination: (1) bilateral GA, (2) early/intermediate AMD, and (3) exudative AMD. GA areas were quantified based on fundus autofluorescence images using a semiautomated image-processing method, and progression rates (PR) were estimated using two-level, linear, mixed-effects models.
   RESULTS. Crude GA-PR in the bilateral GA group (mean, 1.64 mm(2)/y; 95% CI, 1.478-1.803) was significantly higher than in the fellow eye early/intermediate group (0.74 mm(2)/y, 0.1461.342). Although there was a significant difference in baseline GA size (P = 0.0013, t-test), and there was a significant increase in GA-PR by 0.11 mm(2)/y (0.05-0.17) per 1 disc area (DA; 2.54 mm(2)), an additional mean change of -0.79 (-1.43 to -0.15) was given to the PR beside the effect of baseline GA size. However, this difference was only significant when GA size was >= 1 DA at baseline with a GA-PR of 1.70 mm(2)/y (1.54-1.85) in the bilateral and 0.95 mm(2)/y (0.37-1.54) in the early/intermediate group. There was no significant difference in PR compared with that in the fellow eye exudative group.
   CONCLUSIONS. The results indicate that the AMD manifestation of the fellow eye at baseline serves as an indicator for disease progression in eyes with GA >= 1 DA. Predictive characteristics not only contribute to the understanding of pathophysiological mechanisms, but also are useful for the design of future interventional trials in GA patients. (ClinicalTrials.gov number, NCT00393692.) (Invest Ophthalmol Vis Sci. 2011; 52:6552-6557) DOI: 10.1167/iovs.11-7298
C1 [Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Visvalingam, Sivatharisini; Goebel, Arno P.; Holz, Frank G.] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   [Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Visvalingam, Sivatharisini; Goebel, Arno P.; Holz, Frank G.] Univ Bonn, Grade Reading Ctr, D-53127 Bonn, Germany.
   [Adrion, Christine; Mansmann, Ulrich] Univ Munich, Inst Med Informat Sci Biometry & Epidemiol IBE, Munich, Germany.
   [Moessner, Andreas] Univ Leipzig, Dept Ophthalmol, Leipzig, Germany.
   [von Strachwitz, Claudia N.] Univ Wurzburg, Dept Ophthalmol, Wurzburg, Germany.
   [Mackensen, Friederike] Heidelberg Univ, Dept Ophthalmol, Heidelberg, Germany.
   [Pauleikhoff, Daniel] St Franziskus Hosp, Munster, Germany.
   [Wolf, Sebastian] Inselspital Bern, Dept Ophthalmol, CH-3010 Bern, Switzerland.
C3 University of Bonn; University of Bonn; University of Munich; Leipzig
   University; University of Wurzburg; Ruprecht Karls University
   Heidelberg; St. Franziskus-Hospital; University of Bern; University
   Hospital of Bern
RP Holz, FG (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM frank.holz@ukb.uni-bonn.de
RI Wolf, Sebastian/B-8782-2008; Mitchell, Paul/P-1498-2014; Adrion,
   Christine/AAB-7247-2020
OI Wolf, Sebastian/0000-0002-7467-7028; Adrion,
   Christine/0000-0003-2408-2533; Fleckenstein, Monika/0000-0001-8321-8037
FU DFG (German Research Council) [Ho1926/3-1, MA 1723/1-1, Wo478-10];
   BONFOR [0-137-0012]
FX Supported by DFG (German Research Council) Grants Ho1926/3-1, MA
   1723/1-1, and Wo478-10, BONFOR 0-137-0012 (MF). The sponsor or funding
   organization had no role in the design or conduct of this research.
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NR 31
TC 33
Z9 33
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2011
VL 52
IS 9
BP 6552
EP 6557
DI 10.1167/iovs.11-7298
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 815SI
UT WOS:000294548300026
PM 21757586
DA 2022-11-30
ER

PT J
AU Pemp, B
   Polska, E
   Karl, K
   Lasta, M
   Minichmayr, A
   Garhofer, G
   Wolzt, M
   Schmetterer, L
AF Pemp, Berthold
   Polska, Elzbieta
   Karl, Katharina
   Lasta, Michael
   Minichmayr, Alexander
   Garhofer, Gerhard
   Wolzt, Michael
   Schmetterer, Leopold
TI Effects of Antioxidants (AREDS Medication) on Ocular Blood Flow and
   Endothelial Function in an Endotoxin-Induced Model of Oxidative Stress
   in Humans
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MACULAR DEGENERATION; VITAMIN-C; EXPERIMENTAL UVEITIS; BETA-CAROTENE;
   HYPEROXIA; OXYGEN; VASOCONSTRICTION; REACTIVITY; MECHANISM; PRESSURE
AB PURPOSE. The Age-Related Eye Disease Study (AREDS) has shown that supplementation of antioxidants slows the progression of age-related macular degeneration (AMD). The mechanism underlying this therapeutic effect may be related to a reduction of reactive oxygen species (ROS). The authors have recently introduced a model showing that the response of retinal blood flow (RBF) to hyperoxia is diminished by administration of lipopolysaccharide (LPS). In the present study, the hypothesis was that this response can be restored by the AREDS medication.
   METHODS. Twenty-one healthy volunteers were included in this randomized, double-masked, placebo-controlled, parallel group study. On each study day, RBF and the reactivity of RBF to hyperoxia were investigated before and after infusion of 2 ng/kg LPS. Between the two study days, subjects took either the AREDS medication or placebo for 14 days.
   RESULTS. After administration of LPS reduced retinal arterial vasoconstriction during hyperoxia (AREDS group: 12.5% +/- 4.8% pre-LPS vs. 9.4% +/- 4.6% post-LPS; placebo group: 9.2% +/- 3.3% pre-LPS vs. 7.1% +/- 3.5% post-LPS) and a reduced reactivity of RBF during hyperoxia (AREDS: 50.4% +/- 8.9% vs. 44.9% +/- 11.6%, placebo: 54.2% +/- 8.6% vs. 46.0% +/- 6.9%) was found. The reduced responses were normalized after 2 weeks of AREDS antioxidants but not after placebo (vasoconstriction: 13.1% +/- 4.5% vs. 13.1% +/- 5.0% AREDS, 11.2% +/- 4.2 vs. 7.4% +/- 4.2% placebo; RBF: 52.8% +/- 10.5% vs. 52.4% +/- 10.5% AREDS, 52.4% +/- 9.3% vs. 44.2% +/- 6.3% placebo).
   CONCLUSIONS. The sustained retinal vascular reaction to hyperoxia after LPS in the AREDS group indicates that antioxidants reduce oxidative stress-induced endothelial dysfunction, possibly by eliminating ROS. The model may be an attractive approach to studying the antioxidative capacity of dietary supplements for the treatment of AMD (ClinicalTrials.gov number, NCT00431691). (Invest Ophthalmol Vis Sci. 2010; 51: 2-6) DOI: 10.1167/iovs.09-3888
C1 [Pemp, Berthold; Polska, Elzbieta; Karl, Katharina; Lasta, Michael; Minichmayr, Alexander; Garhofer, Gerhard; Wolzt, Michael; Schmetterer, Leopold] Med Univ Vienna, Dept Clin Pharmacol, A-1090 Vienna, Austria.
   [Schmetterer, Leopold] Med Univ Vienna, Ctr Biomed Engn & Phys, A-1090 Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna
RP Schmetterer, L (通讯作者)，Med Univ Vienna, Dept Clin Pharmacol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM leopold.schmetterer@meduniwien.ac.at
OI Wolzt, Michael/0000-0001-6049-1890; Pemp, Berthold/0000-0002-0569-0229;
   Schmetterer, Leopold/0000-0002-7189-1707
CR Baskol G, 2006, OPHTHALMOLOGICA, V220, P12, DOI 10.1159/000089269
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NR 33
TC 22
Z9 25
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JAN
PY 2010
VL 51
IS 1
BP 2
EP 6
DI 10.1167/iovs.09-3888
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 539OI
UT WOS:000273264200002
PM 19684008
DA 2022-11-30
ER

PT J
AU Shtir, CJ
   Marjoram, P
   Azen, S
   Conti, DV
   Le Marchand, L
   Haiman, CA
   Varma, R
AF Shtir, Corina J.
   Marjoram, Paul
   Azen, Stanley
   Conti, David V.
   Le Marchand, Loic
   Haiman, Christopher A.
   Varma, Rohit
TI Variation in genetic admixture and population structure among Latinos:
   the Los Angeles Latino eye study (LALES)
SO BMC GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MULTILOCUS GENOTYPE DATA; SOUTHERN EUROPEAN
   POPULATIONS; INFLAMMATORY-BOWEL-DISEASE; AGE-RELATED MACULOPATHY;
   BREAST-CANCER RISK; MACULAR DEGENERATION; AFRICAN-AMERICANS; LINKAGE
   DISEQUILIBRIUM; MULTIETHNIC COHORT
AB Background: Population structure and admixture have strong confounding effects on genetic association studies. Discordant frequencies for age-related macular degeneration (AMD) risk alleles and for AMD incidence and prevalence rates are reported across different ethnic groups. We examined the genomic ancestry characterizing 538 Latinos drawn from the Los Angeles Latino Eye Study [LALES] as part of an ongoing AMD-association study. To help assess the degree of Native American ancestry inherited by Latino populations we sampled 25 Mayans and 5 Mexican Indians collected through Coriell's Institute. Levels of European, Asian, and African descent in Latinos were inferred through the USC Multiethnic Panel (USC MEP), formed from a sample from the Multiethnic Cohort (MEC) study, the Yoruba African samples from HapMap II, the Singapore Chinese Health Study, and a prospective cohort from Shanghai, China. A total of 233 ancestry informative markers were genotyped for 538 LALES Latinos, 30 Native Americans, and 355 USC MEP individuals (African Americans, Japanese, Chinese, European Americans, Latinos, and Native Hawaiians). Sensitivity of ancestry estimates to relative sample size was considered.
   Results: We detected strong evidence for recent population admixture in LALES Latinos. Gradients of increasing Native American background and of correspondingly decreasing European ancestry were observed as a function of birth origin from North to South. The strongest excess of homozygosity, a reflection of recent population admixture, was observed in non-US born Latinos that recently populated the US. A set of 42 SNPs especially informative for distinguishing between Native Americans and Europeans were identified.
   Conclusion: These findings reflect the historic migration patterns of Native Americans and suggest that while the 'Latino' label is used to categorize the entire population, there exists a strong degree of heterogeneity within that population, and that it will be important to assess this heterogeneity within future association studies on Latino populations. Our study raises awareness of the diversity within "Latinos" and the necessity to assess appropriate risk and treatment management.
C1 [Marjoram, Paul; Azen, Stanley; Conti, David V.; Haiman, Christopher A.; Varma, Rohit] Univ So Calif, Keck Sch Med, Div Biostat, Dept Prevent Med, Los Angeles, CA 90033 USA.
   [Shtir, Corina J.] Univ Calif Los Angeles, Dept Human Genet & Neurosci, Los Angeles, CA 90095 USA.
   [Conti, David V.] Univ So Calif, Keck Sch Med, Dept Environm Hlth, Los Angeles, CA 90033 USA.
   [Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA.
   [Varma, Rohit] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
   [Varma, Rohit] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA.
C3 University of Southern California; University of California System;
   University of California Los Angeles; University of Southern California;
   Cancer Research Center of Hawaii; University of Hawaii System;
   University of Southern California; Doheny Eye Institute; University of
   Southern California
RP Varma, R (通讯作者)，Univ So Calif, Keck Sch Med, Div Biostat, Dept Prevent Med, Los Angeles, CA 90033 USA.
EM stir@usc.edu; pmarjora@usc.edu; sazen@usc.edu; dconti@usc.edu;
   loic@crch.hawaii.edu; haiman@usc.edu; rvarma@usc.edu
FU NCI NIH HHS [CA54281, CA63464] Funding Source: Medline; NEI NIH HHS [P30
   EY003040, EY11753, U10 EY011753, EY03040] Funding Source: Medline; NHGRI
   NIH HHS [HG004049] Funding Source: Medline; NATIONAL CANCER INSTITUTE
   [R01CA063464, R37CA054281, U01CA063464, R01CA054281] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [P30EY003040] Funding Source: NIH
   RePORTER; NATIONAL HUMAN GENOME RESEARCH INSTITUTE [R01HG004049] Funding
   Source: NIH RePORTER
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NR 77
TC 23
Z9 23
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2156
J9 BMC GENET
JI BMC Genet.
PD NOV 10
PY 2009
VL 10
AR 71
DI 10.1186/1471-2156-10-71
PG 13
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 527GP
UT WOS:000272355600001
PM 19903357
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Spaide, RF
AF Spaide, Richard F.
TI Age-Related Choroidal Atrophy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; OPTIC DISK MORPHOMETRY; MACULAR DEGENERATION;
   PERIPAPILLARY ATROPHY; RISK-FACTORS; PREVALENCE; POPULATION;
   MACULOPATHY; MORPHOLOGY
AB PURPOSE: To report the clinical characteristics of it newly defined entity, age,related choroidal atrophy.
   DESIGN: Retrospective, observational case series.
   METHODS: The choroidal thickness was measured in images obtained by positioning a spectral-domain optical coherence tomography device close enough to the eye to acquire an inverted image. Seven sections each comprised of 100 averaged scans were obtained within a 5 x 15-degree or larger rectangle to encompass the macula and temporal juxtapapillary retina. The choroidal thickness of patients less than 125 mu m in thickness were included, whereas eyes with myopia of 6 diopters or more, a history of uveitis, trauma, ionizing radiation, photodynamic therapy, intravitreal corticosteroid injection, or tapetoretinal dystrophy were excluded. The patients were evaluated for Visual acuity, macular appearance, and the presence of glaucoma.
   RESULTS: There were 28 eligible eyes of 17 patients with a mean age 80.6 years (standard deviation, +/- 7.3 years). All eyes had a tessellated fundus appearance. The mean subfoveal choroidal thickness was 69.8 mu m and became even more attenuated nasally. Of the 18 eyes that had no evidence of late age-related macular degeneration (AMD), the mean Visual acuity was 20/40, there were pigmentary changes in the macula that arose in part from the choroid potentially mimicking early AMD, and a rarefaction of the choroidal vessels under the macula. Concurrent late AMD was found in the 10 remaining eyes. Glaucoma was present in 6 patients (35.3%), all of whom had peripapillary atrophy. The choroid was seen to become nearly obliterated before the demarcation of the P-zone of peripapillary atrophy.
   CONCLUSIONS: Age-related choroidal atrophy affects older individuals in whom posterior pole abnormalities develop that may mimic and also be associated with findings typical for AMD. Patients with age-related choroidal atrophy may be at higher risk for glaucoma. (Am J Ophthalmol 2009;147:801-810. Q 2009 by Elsevier Inc. All rights reserved.)
C1 [Spaide, Richard F.] Vitreous Retina Macula Consultants New York, New York, NY 10022 USA.
   [Spaide, Richard F.] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA.
C3 Vitreous Retina Macula Consultants of New York; Manhattan Eye Ear &
   Throat Hospital
RP Spaide, RF (通讯作者)，Vitreous Retina Macula Consultants New York, 460 Pk Ave,5th Floor, New York, NY 10022 USA.
EM rickspaide@yahoo.com
RI Spaide, Richard/ABD-7368-2020
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NR 32
TC 263
Z9 277
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD MAY
PY 2009
VL 147
IS 5
BP 801
EP 810
DI 10.1016/j.ajo.2008.12.010
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 441IQ
UT WOS:000265762900009
PM 19232561
DA 2022-11-30
ER

PT J
AU Newsome, DA
   Negreiro, M
AF Newsome, David A.
   Negreiro, Manny
TI Reproducible Measurement of Macular Light Flash Recovery Time Using a
   Novel Device Can Indicate the Presence and Worsening of Macular Diseases
SO CURRENT EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; diabetic maculopathy; macular edema;
   macular light flash recovery timer; macular photorecovery; retinal dark
   adaptation; wet age-related macular degeneration
ID PHOTOSTRESS RECOVERY; DARK-ADAPTATION; CLINICAL-TRIAL
AB Purpose: To determine the safety, sensitivity, and specificity of a novel flash photorecovery timing instrument with response verification in differentiating normal from abnormal maculae, and in detecting worsening macular disease. Methods: Right and left eye photorecovery times were determined at baseline and after 5 min using a xenon arc, flash filtered for infrared, ultraviolet, and visible short wavelengths, delivered through an aperture in a hand-held tube. A push-button actuated timer and flash and stopped timer when lighted numbers became visible post-flash. A numeric keypad verified responses. Normal subjects (two eyes tested, n = 144; one eye tested, n = 108) ranged in age from 15 to 84. Photorecovery times were measured in one eye of subjects with small drusen and 20/20 acuity (53-55 correct ETDRS letters; n = 57); in both eyes of subjects with dry age-related macular degeneration (AMD; n = 118); wet AMD with (n = 19) or without (n = 17) macular fluid; and eyes of diabetics with background retinopathy with (n = 19) or without (n = 17) macular retinal thickening. Once-weekly photorecovery measurements for 6 months in each eye of 10 dry AMD subjects and 10 dry diabetic maculopathy subjects provided longitudinal data. Results: Normal subjects' mean right eye recovery time was 9.6 sec ( 1.9 SD); left 10.8 sec ( 1.0 SD). Photorecovery lengthened after age 55, nearly doubling that of young subjects by age 80. Macular edema, serous macular detachment, or worsened dry AMD were accompanied by prolonged photorecovery (p .01). When abnormal new vessels or retinal thickening appeared in three serially followed patients, photorecovery at least doubled (p .01). In all three, photorecovery prolongation occurred without clinical symptoms. None of the 499 tested subjects reported adverse events due to the flash testing. Conclusions: These findings support the usefulness of a reproducible light flash macular vision recovery measurement as an indicator of macular pathology and worsening disease.
C1 [Newsome, David A.; Negreiro, Manny] Retinal Inst Louisiana, New Orleans, LA USA.
RP Newsome, DA (通讯作者)，1764 Brightwaters Blvd NE, St Petersburg, FL 33704 USA.
EM doctordave1618@aol.com
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NR 47
TC 18
Z9 20
U1 0
U2 7
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PY 2009
VL 34
IS 2
BP 162
EP 170
AR PII 908701516
DI 10.1080/02713680802647654
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 407LX
UT WOS:000263366800011
PM 19219688
DA 2022-11-30
ER

PT J
AU Renner, AB
   Tillack, H
   Kraus, H
   Kramer, F
   Mohr, N
   Weber, BHF
   Foerster, MH
   Kellner, U
AF Renner, AB
   Tillack, H
   Kraus, H
   Kramer, F
   Mohr, N
   Weber, BHF
   Foerster, MH
   Kellner, U
TI Late onset is common in best macular dystrophy associated with VMD2 gene
   mutations
SO OPHTHALMOLOGY
LA English
DT Article
ID BEST-DISEASE; MULTIFOCAL ELECTRORETINOGRAPHY; RETINAL DYSFUNCTION;
   DEGENERATION; ERG; ELECTROOCULOGRAPHY; MACULOPATHIES; RETINOPATHY;
   LIPOFUSCIN
AB Purpose: To perform a detailed morphologic and functional evaluation of Best macular dystrophy (BMD) associated with mutations in the VMD2 gene.
   Design: Retrospective study.
   Participants: The records of 16 patients with BMD and heterozygous VMD2 mutations (group 1) and 5 patients with Best-like lesions with no detectable disease-associated alterations in the VMD2 gene (group 2) were evaluated retrospectively.
   Methods: The data were reviewed regarding visual acuity (VA), color vision, perimetry, autofluorescence of the retinal pigment epithelium (RPE), fluorescein angiography, electro-oculography (EOG), and full-field electroretinography (ERG) and multifocal ERG (mfERG).
   Main Outcome Measures: VMD2 mutations, age at onset of BMD, RPE autofluorescence, EOG, ERG, and mfERG.
   Results: The mean age of the patients in group 1 was 47.1 years (range, 16.7-86.5), and age at onset varied between 5 and 58 years (median, 42.0). Visual acuity ranged between 20/16 and 20/400 (median, 20/40). No association existed between the specific nature of the VMD2 mutation and disease onset or expressivity. Retinal pigment epithelium autofluorescence was increased corresponding to ophthalmoscopically visible yellow material, whereas it was decreased in the atrophic stage of BMD. Electro-oculography light rise was reduced in 18 of 19 eyes. Electroretinography amplitudes were normal in 3 patients and reduced in 6 patients. Multifocal ERG revealed in 10 of 20 eyes a central amplitude reduction and in 7 eyes a generalized one. There were no marked differences in clinical and functional findings between the patients in groups 1 and 2, except that the mean age of the patients in group 2 was higher (64.0 years [range, 45.7-80.6]) and the median VA lower (20/50 [range, 20/32-20/320]).
   Conclusions: The onset of BMD is highly variable and occurred in the majority of patients after the second decade of life. Best-like lesions may develop in older patients without associated VMD2 mutations. Those manifestations may be related to a specific form of age-related macular degeneration. (c) 2005 by the American Academy of Ophthalmology.
C1 Univ Med Berlin, Augenklin, D-12200 Berlin, Germany.
   Biozentrum, Inst Human Genet, Wurzburg, Germany.
   RetinaSci, Bonn, Germany.
C3 Free University of Berlin; Humboldt University of Berlin; Charite
   Universitatsmedizin Berlin; University of Hamburg; University Medical
   Center Hamburg-Eppendorf; University of Wurzburg
RP Renner, AB (通讯作者)，Univ Med Berlin, Augenklin, Charite Campus Benjamin Franklin,Hindenburgdamm 3, D-12200 Berlin, Germany.
EM a.renner@berlin.de
OI Weber, Bernhard H.F./0000-0002-8808-7723
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NR 26
TC 78
Z9 80
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD APR
PY 2005
VL 112
IS 4
BP 586
EP 592
DI 10.1016/j.ophtha.2004.10.041
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 910WF
UT WOS:000227962200010
PM 15808248
DA 2022-11-30
ER

PT J
AU Massof, RW
AF Massof, RW
TI A model of the prevalence and incidence of low vision and blindness
   among adults in the US
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE low vision; blindness; visual acuity; prevalence; incidence; visual
   impairment
ID BALTIMORE EYE SURVEY; BEAVER-DAM EYE; VISUAL IMPAIRMENT; POPULATION;
   ACUITY
AB Population-based vision screening studies of the prevalence rate of low vision and blindness in the U.S. are reviewed to evaluate the sources of disagreement among studies. The major reasons that studies disagree on prevalence rate estimates are differences in best-corrected visual acuity criteria for low vision and differences in the age range of the oldest age category. When corrections are made for these differences, the results of all prevalence rate studies, except the Mud Creek Valley Study, fit the same prevalence rate vs. age function. The greater prevalence rate of low vision and blindness for each age category that was observed in the Mud Creek Valley Study can be attributed to the higher prevalence rate of cataract associated with a paucity of health care services in the Mud Creek Valley population. The time-derivative of the prevalence rate vs. age function fit to the data provided an estimate of the annual incidence rate of low vision and blindness vs. age. The estimated annual incidence agreed with estimates from unpublished 8-year incidence data of the Baltimore Eye Survey. The incidence rate of low vision and blindness for Americans aged 40 to 60 years is higher among blacks than among whites. For Americans greater than age 60 years, the incidence rate for whites exceeds that for blacks. This observation probably reflects the different natural histories of glaucoma, a leading cause of low vision and blindness among black Americans, and age-related macular degeneration, a leading cause of low vision and blindness among white Americans. Using the age-dependent models of prevalence rate of low vision and blindness for white and black populations, an estimated 1.5 million Americans over age 45 years have a best-corrected visual acuity in the better eye that is less than or equal to20/70. Based on the incidence rate estimates, approximately 240,000 new cases of low vision and blindness occur each year. With the aging of the U.S. population, that number is expected to double over the next 25 years.
C1 Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Lions Vis Res & Rehabil Ctr, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Massof, RW (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Lions Vis Res & Rehabil Ctr, 550 N Broadway,6th Floor, Baltimore, MD 21205 USA.
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NR 22
TC 55
Z9 56
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-5488
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD JAN
PY 2002
VL 79
IS 1
BP 31
EP 38
DI 10.1097/00006324-200201000-00010
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 528BJ
UT WOS:000174223400004
PM 11828896
DA 2022-11-30
ER

PT J
AU Ziemssen, F
   Hammer, T
   Grueb, M
   Mueller, B
   Berk, H
   Gamulescu, MA
   Voegeler, J
   Wachtlin, J
AF Ziemssen, Focke
   Hammer, Thomas
   Grueb, Matthias
   Mueller, Bettina
   Berk, Husnu
   Gamulescu, Maria-Andreea
   Voegeler, Jessica
   Wachtlin, Joachim
CA OCEAN Study Grp
TI Reporting of Safety Events during Anti-VEGF Treatment: Pharmacovigilance
   in a Noninterventional Trial
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID DIABETIC MACULAR EDEMA; ADVERSE DRUG-REACTIONS; GERMAN HEALTH INTERVIEW;
   RETINAL VEIN OCCLUSION; CORONARY-HEART-DISEASE; GROWTH-FACTOR THERAPY;
   INTRAVITREAL INJECTION; SYSTEMIC SAFETY; RANIBIZUMAB; PREVALENCE
AB Aim. The prospective, noninterventional OCEAN study assessed the safety of intravitreal ranibizumab injections for treatment of neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion under real-world conditions in Germany.Methods. Adults receiving >= 1 ranibizumab (0.5 mg) injections were recruited by 369 ophthalmologists and followed for 24 months. Information on adverse events (AEs) was reported by the treating physician or detected by the data management team. Collected information included observed AE, AE start and end date, intensity, causal relationship, outcome, severity, suspected drug, and actions taken.Results. 2,687 AEs were reported for 1,176 of the 5,781 patients who had received a total of 32,621 injections: 27.4% nonserious AEs, 30.3% serious AEs, 27.3% nonserious adverse drug reactions (ADRs), and 15.0% serious ADRs. Most patients reported no AEs (79.7%) or only 1 AE (10.3%). AEs were most commonly reported in the Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) Eye disorders (9.4% of patients) and General disorders and administration site conditions (5.8%). The most frequent AEs by MedDRA preferred term (PT) were visual acuity reduced (3.5% of patients), intraocular pressure increased (2.5%), and drug ineffective (2.1%). AEs occurred most frequently after 3 or 4 injections (1,129 of 2,687 AEs). The proportion of AEs in the SOC Eye disorders decreased slightly with increasing number of injections, from 39.8% of events after 1 or 2 injections to 29.1% after 5 or more injections. Rates of the most frequently reported PTs did not show any consistent increase with increasing number of injections. A decrease in overall AE rates was observed over the study course.Conclusions. The results did not raise any new safety concerns for ranibizumab. The findings allow conclusions to be drawn on how pharmacovigilance data can be collected even more effectively in real-world studies to facilitate discussion on benefit-risk ratio.
C1 [Ziemssen, Focke; Grueb, Matthias; OCEAN Study Grp] Eberhard Karls Univ Tuebingen, Ctr Ophthalmol, D-72076 Tubingen, Germany.
   [Hammer, Thomas] Augenzentrum Halle, Dessauer Str 194, D-06118 Halle, Germany.
   [Hammer, Thomas] Martin Luther Univ Halle Wittenberg, Univ Klin & Poliklin Augenheilkunde, Ernst Grube Str 40, D-06112 Halle, Germany.
   [Grueb, Matthias] Augenarztpraxis Villa Lindengarten, Breisach, Germany.
   [Mueller, Bettina; Voegeler, Jessica] Novartis Pharma GmbH, D-90429 Nurnberg, Germany.
   [Berk, Husnu] St Elisabeth Klin Hohenlind, Cologne, Germany.
   [Gamulescu, Maria-Andreea] Univ Augenklin Regensburg, Franz Josef Str Allee 11, D-93051 Regensburg, Germany.
   [Wachtlin, Joachim] Sankt Gertrauden Krankenhaus, Dept Ophthalmol, Paretzer Str 12, D-10713 Berlin, Germany.
   [Wachtlin, Joachim] MHB Med Hsch Brandenburg, Neuruppin, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Martin Luther University Halle Wittenberg; Novartis;
   University of Regensburg
RP Ziemssen, F (通讯作者)，Eberhard Karls Univ Tuebingen, Ctr Ophthalmol, D-72076 Tubingen, Germany.
EM focke.ziemssen@med.uni-tuebingen.de
RI Ziemssen, Focke/AAY-1686-2021
OI Ziemssen, Focke/0000-0002-3873-0581
FU Novartis Pharma GmbH, Nuremberg, Germany
FX The authors thank Klaus Laschke (statistics), Susanne Faber (project
   management), Daniela Mueller and Catherine Mason (medical writing), and
   all Kantar GmbH, Munich, Germany, for their assistance, which was funded
   by Novartis Pharma GmbH, Nuremberg, Germany. The OCEAN study and the
   preparation and publication of this article was funded by Novartis
   Pharma GmbH, Nuremberg, Germany
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NR 55
TC 3
Z9 3
U1 0
U2 0
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PD OCT 6
PY 2020
VL 2020
AR 8652370
DI 10.1155/2020/8652370
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ON1BQ
UT WOS:000586446100001
PM 33083052
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Wu, T
   Dang, KR
   Wang, YF
   Lyu, BZ
   Xu, WQ
   Dou, GR
   Zhou, J
   Hui, YN
   Du, HJ
AF Wu, Tong
   Dang, Kuan-Rong
   Wang, Ya-Fen
   Lyu, Bao-Zhen
   Xu, Wen-Qin
   Dou, Guo-Rui
   Zhou, Jian
   Hui, Yan-Nian
   Du, Hong-Jun
TI A modified laser-induced choroidal neovascularization animal model with
   intravitreal oxidized low-density lipoprotein
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization; oxidized
   low-density lipoprotein; animal model
ID MACULAR DEGENERATION; RECEPTOR-1; APOPTOSIS; EYE
AB AIM: To investigate whether intravitreal injection of oxidized low-density lipoprotein (OxLDL) can promote laser-induced choroidal neovascularization (CNV) formation in mice and the mechanism involved, thereby to develop a better animal model.
   METHODS: C57BL6/J mice were randomized into three groups. Immediately after CNV induction with 532 nm laser photocoagulation, 1.0 mu L of OxLDL [100 mu g/mL in phosphate-buffered saline (PBS)] was intravitreally injected, whereas PBS and the same volume low-density lipoprotein (LDL; 100 mu g/mL in PBS) were injected into the vitreous as controls. Angiogenic and inflammatory cytokines were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) after 5d, and CNV severity was analyzed by choroid flat mount and immunofluorescence staining after 1wk. In vitro, retinal pigment epithelial (RPE) cell line (ARPE19) were treated with OxLDL (LDL as control) for 8h. Angiogenic and inflammatory cytokine levels were measured. A specific inhibitor of lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) was used to evaluate the role of LOX1 in this process.
   RESULTS: At 7d after intravitreal injection of 1 mu L (100 mu g/mL) OxLDL, T15-labeled OxLDL was mainly deposited around the CNV area, and the F4/80-labeled macrophages, the CD31-labeled vascular endothelial cells number and CNV area were increased. Meanwhile, WB and qRT-PCR results showed that vascular endothelial growth factor (VEGF), CC chemokine receptor 2 (CCR2), interleukin-6 (IL-6), IL-1 beta, and matrix metalloproteinase 9 (MMP9) expressions were increased, which was supported by in vitro experiments in RPE cells. LOX1 inhibitors significantly reduced expressions of inflammatory factors IL-1 beta and VEGF.
   CONCLUSION: A modified laser-induced CNV animal model is established with intravitreal injection of 1 mu L (100 mu g/mL) of OxLDL at 7d, which at least partially through LOX1. This animal model can be used as a simple model for studying the role of OxLDL in age-related macular degeneration.
C1 [Wu, Tong; Dang, Kuan-Rong; Wang, Ya-Fen; Dou, Guo-Rui; Zhou, Jian; Hui, Yan-Nian; Du, Hong-Jun] Fourth Mil Med Univ, Xijing Hosp, Eye Inst Chinese PLA, Dept Ophthalmol, Xian 710032, Shaanxi, Peoples R China.
   [Lyu, Bao-Zhen] Xian Hlth Sch, Dept Anat & Histol & Embryol, Xian 710032, Shaanxi, Peoples R China.
   [Xu, Wen-Qin] Peoples Liberat Army Gen Hosp, Med Ctr 3, Orbital Dis Inst, Beijing 100039, Peoples R China.
C3 Air Force Military Medical University; Chinese People's Liberation Army
   General Hospital
RP Hui, YN; Du, HJ (通讯作者)，Fourth Mil Med Univ, Xijing Hosp, Eye Inst Chinese PLA, Dept Ophthalmol, Xian 710032, Shaanxi, Peoples R China.
EM fmmuhyn@fmmu.edu.cn; dhj2020@126.com
FU National Natural Science Foundation of China [81470654]; Science and
   Technology Plan of Natural Science Foundation of Shaanxi Province
FX Supported by the National Natural Science Foundation of China
   (No.81470654); Science and Technology Plan of Natural Science Foundation
   of Shaanxi Province (No.2019SF-047).
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NR 29
TC 0
Z9 1
U1 0
U2 2
PU IJO PRESS
PI XI AN
PA NO 269 YOUYI EAST RD, XI AN, 710054, PEOPLES R CHINA
SN 2222-3959
EI 2227-4898
J9 INT J OPHTHALMOL-CHI
JI Int. J. Ophthalmol.
PD AUG 18
PY 2020
VL 13
IS 8
BP 1187
EP 1194
DI 10.18240/ijo.2020.08.03
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MX4VA
UT WOS:000557721200003
PM 32821671
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Abokyi, S
   Shan, SW
   To, CH
   Chan, HHL
   Tse, DYY
AF Abokyi, Samuel
   Shan, Sze Wan
   To, Chi-ho
   Chan, Henry Ho-lung
   Tse, Dennis Yan-yin
TI Autophagy Upregulation by the TFEB Inducer Trehalose Protects against
   Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human
   RPE Cells
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; CHAPERONE-MEDIATED AUTOPHAGY; AUTOLYSOSOME
   FORMATION; SUBSTRATE SQSTM1/P62; CIGARETTE-SMOKING; AGE; ACTIVATION;
   STRESS; EXPRESSION; DEGRADATION
AB Trehalose is a natural dietary molecule that has shown antiaging and neuroprotective effects in several animal models of neurodegenerative diseases. The role of trehalose in the management of age-related macular degeneration (AMD) is yet to be investigated and whether trehalose could be a remedy for the treatment of diseases linked to oxidative stress and NRF2 dysregulation. Here, we showed that incubation of human retinal pigment epithelial (RPE) cells with trehalose enhanced the mRNA and protein expressions of TFEB, autophagy genes ATG5 and ATG7, as well as protein expressions of macroautophagy markers, LC3B and p62/SQTM1, and the chaperone-mediated autophagy (CMA) receptor LAMP2. Cathepsin D, a hydrolytic lysosomal enzyme, was also increased by trehalose, indicating higher proteolytic activity. Moreover, trehalose upregulated autophagy flux evident by an increase in the endogenous LC3B level, and accumulation of GFP-LC3B puncta and free GFP fragments in GFP-LC3 boxed times expressing cells in the presence of chloroquine. In addition, the mRNA levels of key molecular targets implicated in RPE damage and AMD, such as vascular endothelial growth factor- (VEGF-) A and heat shock protein 27 (HSP27), were downregulated, whereas NRF2 was upregulated by trehalose. Subsequently, we mimicked in vitro AMD conditions using hydroquinone (HQ) as the oxidative insult on RPE cells and evaluated the cytoprotective effect of trehalose compared to vehicle treatment. HQ depleted NRF2, increased oxidative stress, and reduced the viability of cells, while trehalose pretreatment protected against HQ-induced toxicity. The cytoprotection by trehalose was dependent on autophagy but not NRF2 activation, since autophagy inhibition by shRNA knockdown of ATG5 led to a loss of the protective effect. The results support the transcriptional upregulation of TFEB and autophagy by trehalose and its protection against HQ-induced oxidative damage in RPE cells. Further investigation is, therefore, warranted into the therapeutic value of trehalose in alleviating AMD and retinal diseases associated with impaired NRF2 antioxidant defense.
C1 [Abokyi, Samuel; Shan, Sze Wan; To, Chi-ho; Chan, Henry Ho-lung; Tse, Dennis Yan-yin] Hong Kong Polytech Univ, Sch Optometry, Hong Kong, Peoples R China.
   [Abokyi, Samuel] Univ Cape Coast, Dept Optometry & Vis Sci, Cape Coast, Ghana.
C3 Hong Kong Polytechnic University; University of Cape Coast
RP Tse, DYY (通讯作者)，Hong Kong Polytech Univ, Sch Optometry, Hong Kong, Peoples R China.
EM samuel.abokyi@connect.polyu.hk; samantha.shan@polyu.edu.hk;
   chi-ho.to@polyu.edu.hk; henryhl.chan@polyu.edu.hk;
   dennis.tse@polyu.edu.hk
RI TSE, Dennis Yan-yin/B-9949-2011
OI TSE, Dennis Yan-yin/0000-0001-7561-9121; SHAN, SW/0000-0001-6876-9914;
   ABOKYI, SAMUEL/0000-0001-8808-1340; CHAN, Henry HL/0000-0002-8516-4711
FU Henry G. Leong Endowed Professorship in Elderly Vision Health; PolyU
   Central Research Grants [1ZE6H, 1ZE1A]; General research fund of the
   Hong Kong Research Grants Council [PolyU 151060/18M]; Hong Kong Ph.D.
   Fellowship [UGC/GEN/456/08, UGC/456/09]
FX This study was funded by the Henry G. Leong Endowed Professorship in
   Elderly Vision Health, PolyU Central Research Grants 1ZE6H and 1ZE1A,
   General research fund of the Hong Kong Research Grants Council: PolyU
   151060/18M, and the Hong Kong Ph.D. Fellowship UGC/GEN/456/08,
   UGC/456/09. We are grateful to Mr KK Li (School of Optometry, PolyU) for
   his help with general lab work, and Dr Maureen Boost for proofreading
   the manuscript. Also, we acknowledge The University Research Facility in
   Life Sciences (ULS) of The Hong Kong Polytechnic University and its
   staff, Dr. Hoyin Chow and Dr. Michael Yuen, for the technical
   assistance.
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NR 82
TC 16
Z9 16
U1 3
U2 9
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1942-0900
EI 1942-0994
J9 OXID MED CELL LONGEV
JI Oxidative Med. Cell. Longev.
PD JUL 22
PY 2020
VL 2020
AR 5296341
DI 10.1155/2020/5296341
PG 18
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA MZ4ZC
UT WOS:000559132700003
PM 32774677
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Rozanowska, M
   Edge, R
   Land, EJ
   Navaratnam, S
   Sarna, T
   Truscott, TG
AF Rozanowska, Malgorzata
   Edge, Ruth
   Land, Edward J.
   Navaratnam, Suppiah
   Sarna, Tadeusz
   Truscott, T. George
TI Scavenging of Retinoid Cation Radicals by Urate, Trolox, and -, -, -,
   and -Tocopherols
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE vitamin A; retinol; retinal; retinoic acid; vitamin E; tocopherol; free
   radicals; antioxidants; skin; retina
ID LASER FLASH-PHOTOLYSIS; ALL-TRANS RETINOL; VITAMIN-E;
   LIPID-PEROXIDATION; ALPHA-TOCOPHEROL; MACULAR DEGENERATION;
   PULSE-RADIOLYSIS; OXIDATIVE STRESS; NATURAL FORMS; AGE
AB Retinoids are present in human tissues exposed to light and under increased risk of oxidative stress, such as the retina and skin. Retinoid cation radicals can be formed as a result of the interaction between retinoids and other radicals or photoexcitation with light. It has been shown that such semi-oxidized retinoids can oxidize certain amino acids and proteins, and that -tocopherol can scavenge the cation radicals of retinol and retinoic acid. The aim of this study was to determine (i) whether -, -, and -tocopherols can also scavenge these radicals, and (ii) whether tocopherols can scavenge the cation radicals of another form of vitamin Aretinal. The retinoid cation radicals were generated by the pulse radiolysis of benzene or aqueous solution in the presence of a selected retinoid under oxidizing conditions, and the kinetics of retinoid cation radical decays were measured in the absence and presence of different tocopherols, Trolox or urate. The bimolecular rate constants are the highest for the scavenging of cation radicals of retinal, (7 to 8) x 10(9) M(-1)s(-1), followed by retinoic acid, (0.03 to 5.6) x 10(9) M(-1)s(-1), and retinol, (0.08 to 1.6) x 10(8) M(-1)s(-1). Delta-tocopherol is the least effective scavenger of semi-oxidized retinol and retinoic acid. The hydrophilic analogue of -tocopherol, Trolox, is substantially less efficient at scavenging retinoid cation radicals than -tocopherol and urate, but it is more efficient at scavenging the cation radicals of retinoic acid and retinol than -tocopherol. The scavenging rate constants indicate that tocopherols can effectively compete with amino acids and proteins for retinoid cation radicals, thereby protecting these important biomolecules from oxidation. Our results provide another mechanism by which tocopherols can diminish the oxidative damage to the skin and retina and thereby protect from skin photosensitivity and the development and/or progression of changes in blinding retinal diseases such as Stargardt's disease and age-related macular degeneration (AMD).
C1 [Rozanowska, Malgorzata] Cardiff Univ, Cardiff Inst Tissue Engn & Repair, Cardiff CF10 3AX, S Glam, Wales.
   [Rozanowska, Malgorzata] Cardiff Univ, Sch Optometry & Vis Sci, Cardiff CF24 4HQ, S Glam, Wales.
   [Edge, Ruth] Univ Manchester, Dalton Cumbrian Facil, Westlakes Sci Pk, Moor Row CA24 3HA, Cumbria, England.
   [Land, Edward J.] STFC, Daresbury Lab, Free Radical Res Facil, Warrington WA4 4AD, Cheshire, England.
   [Navaratnam, Suppiah] Univ Salford, Biomed Sci Res Inst, Salford M5 4WT, Lancs, England.
   [Sarna, Tadeusz] Jagiellonian Univ, Fac Biotechnol, Dept Biophys, PL-30387 Krakow, Poland.
   [Truscott, T. George] Keele Univ, Sch Chem & Phys Sci, Lennard Jones Bldg, Keele ST5 5BG, Staffs, England.
C3 Cardiff University; Cardiff University; University of Manchester; STFC
   Daresbury Laboratory; UK Research & Innovation (UKRI); Science &
   Technology Facilities Council (STFC); University of Salford;
   Jagiellonian University; Keele University
RP Rozanowska, M (通讯作者)，Cardiff Univ, Cardiff Inst Tissue Engn & Repair, Cardiff CF10 3AX, S Glam, Wales.; Rozanowska, M (通讯作者)，Cardiff Univ, Sch Optometry & Vis Sci, Cardiff CF24 4HQ, S Glam, Wales.
EM RozanowskaMB@cardiff.ac.uk; Ruth.Edge@manchester.ac.uk;
   E.Land@mighty-micro.co.uk; Navaratnam1000@gmail.com;
   Tadeusz.Sarna@uj.edu.pl; T.G.Truscott@keele.ac.uk
RI Edge, Ruth/J-5268-2019; Rozanowska, Malgorzata/AAD-4806-2021
OI Edge, Ruth/0000-0002-9144-041X; Rozanowska,
   Malgorzata/0000-0003-2913-8954
FU European Union Vth Framework Programme [ICAI-CT-2000-70012]; Wellcome
   Trust Travelling Fellowship; European Commission Human Potential
   Programme Access to Infrastructure [HPRI-CT-2002-00183]
FX This work was supported by theWellcome Trust Travelling Fellowship to M.
   R., and the European Union Vth Framework Programme (Contract
   ICAI-CT-2000-70012). The pulse radiolysis experiments were performed at
   the Free Radical Research Facility at Daresbury Synchrotron Laboratory
   and supported by the European Commission Human Potential Programme
   Access to Infrastructure (Contract HPRI-CT-2002-00183).
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NR 70
TC 8
Z9 8
U1 0
U2 6
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD JUN 1
PY 2019
VL 20
IS 11
AR 2799
DI 10.3390/ijms20112799
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA IE8OX
UT WOS:000472634100193
PM 31181693
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Wells, JA
   Gonzales, CR
   Berger, BB
   Gonzalez, VH
   Sippy, BD
   Burian, G
AF Wells, John A.
   Gonzales, Christine R.
   Berger, Brian B.
   Gonzalez, Victor H.
   Sippy, Brian D.
   Burian, Gabriela
TI A Phase 1, Open-Label, Dose-Escalation Trial to Investigate Safety and
   Tolerability of Single Intravitreous Injections of ICON-1 Targeting
   Tissue Factor in Wet AMD
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; IMMUNOTHERAPY;
   ANGIOGENESIS; INFLAMMATION; THROMBOSIS; EXPRESSION; CANCER
AB BACKGROUND AND OBJECTIVE: This phase 1 study evaluated the safety and tolerability of single intravitreous in- jections (IVIs) of ICON-1 (Iconic Therapeutics, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD), ICON-1 is a modified factor Vila protein linked with the Fc portion of a human immunoglobulin Gl. The molecule binds tissue factor overexpressed on choroidal neovascularization (CNV) in AMD.
   PATIENTS AND METHODS: Open-label, interventional, dose-escalation trial in 18 patients with CNV due to AMD, with six patients per dose cohort. Patients received a single IVI of ICON-1 at baseline in one of three escalating doses: 60 mu g, 150 mu g, or 300 mu g. Standard anti-vascular endothelial growth factor treatment was allowed at the investigator's discretion at least 2 weeks after the ICON-1 injection; patients were followed up to 24 weeks. Dose escalation was based on the absence of significant safety events. At each study visit, best-corrected visual acuity (BCVA), ophthalmic examination (intraocular pressure, slit-lamp, and dilated fundus examination), and ophthalmic imaging (color fundus photography, fluorescein angiography, and optical coherence tomography) assessments were performed. The systemic pharmacokinetics of ICON-1 and presence of anti-ICON-1 antibodies were also assessed.
   RESULTS: ICON-1 was safe and well-tolerated up to the highest dose administered, which was 300 mu g. Commonly reported adverse events were considered related to the IVI procedure or to the underlying nAMD. No significant systemic levels of ICON-1 or anti-ICON-1 antibodies were detected. Preliminary evidence of biological activity (improved BCVA, reduced central retinal thickness, decreased CNV size, and leakage) was most evident with the 300 mu g dose at 1 to 2 weeks after the single ICON-1 injection.
   CONCLUSION: Intravitreous administration of ICON-1 in single doses up to 300 mu g in eyes with neovascular AMD was safe and well-tolerated.
C1 [Wells, John A.] Palmetto Retina Ctr, 2750 Laurel St,Suite 101, W Columbia, SC 29204 USA.
   [Gonzales, Christine R.] Retina & Vitreous Ctr Southern Oregon, Ashland, OR USA.
   [Berger, Brian B.] Retina Res Ctr, Austin, TX USA.
   [Gonzalez, Victor H.] Valley Retina Inst, Mcallen, VA USA.
   [Burian, Gabriela] GB Biomed Advisors GmbH, Oberwil, BL, Switzerland.
RP Wells, JA (通讯作者)，Palmetto Retina Ctr, 2750 Laurel St,Suite 101, W Columbia, SC 29204 USA.
EM jackwells@palmettoretina.com
FU Iconic Therapeutics, South San Francisco, CA; Iconic Therapeutics
FX Iconic Therapeutics, South San Francisco, CA, sponsored the study. The
   sponsor participated in study design and conduct, data collection, data
   management, data analysis and interpretation, and preparation and
   reviews of manuscript. Drs. Wells, Gonzales, Berger, Gonzalez, and Sippy
   participated each as clinical study investigators and received
   institutional financial support to conduct the study.; Drs. Wells and
   Gonzales received advisory board consulting fees from Iconic
   Therapeutics. Dr. Burian received consultant and financial support from
   Iconic Therapeutics.
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NR 13
TC 8
Z9 8
U1 0
U2 2
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD MAY
PY 2018
VL 49
IS 5
BP 336
EP 345
DI 10.3928/23258160-20180501-07
PG 10
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA GG9DF
UT WOS:000433000200007
PM 29772044
OA hybrid, Green Submitted
DA 2022-11-30
ER

PT J
AU Fields, MA
   Bowrey, HE
   Gong, J
   Moreira, EF
   Cai, H
   Del Priore, LV
AF Fields, Mark A.
   Bowrey, Hannah E.
   Gong, Jie
   Moreira, Ernesto F.
   Cai, Hui
   Del Priore, Lucian V.
TI Extracellular matrix nitration alters growth factor release and
   activates bioactive complement in human retinal pigment epithelial cells
SO PLOS ONE
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION;
   BRUCHS MEMBRANE; NATURAL COURSE; DRUSEN; VEGF; RPE; EXPRESSION; PROTEINS
AB Purpose
   We have shown previously that non-enzymatic nitration (NEN) of the extracellular matrix (ECM), which serves as a model of Bruch's membrane (BM) aging, has a profound effect on the behavior of the overlying retinal pigment epithelial (RPE) cells, including altered phagocytic ability, reduced cell adhesion, and inhibition of proliferation. We know that transplanted RPE monolayers will encounter a hostile sub-RPE environment, including age-related alterations in BM that may compromise cell function and survival. Here we use our previous NEN model of BM aging to determine the effects of NEN of the ECM on growth factor release and complement activation in RPE cells.
   Methods
   Human induced-pluripotent stem cells (iPSCs) were differentiated into RPE cells, and confirmed by immunohistochemistry, confocal microscopy, and polymerase chain reaction. IPSC-derived RPE cells were plated onto RPE-derived ECM under untreated or nitrite-modified conditions. Cells were cultured for 7 days and barrier function measured by transepithelial resistance (TER). Vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), and complement component C3a were measured using enzyme-linked immunosorbent assay (ELISA).
   Results
   On average nitrite-modified ECM increased VEGF release both apically and basally by 0.15 +/- 0.014 ng/mL (p < 0.0001) and 0.21 +/- 0.022 ng/mL (p < 0.0001), respectively, in iPSC-derived RPE cells. Nitrite-modified ECM increased PEDF release in iPSC-derived RPE cells apically by 0.16 +/- 0.031 ng/mL (p < 0.0001), but not basally (0.27 +/- 0.015 vs. 0.32 +/- 0.029 ng/mL, (p > 0.05)). Nitrite-modified ECM increased production of C3a in iPSC-derived RPE cells by 0.52 +/- 0.123 ng/mL (p < 0.05).
   Conclusion
   Nitrite-modified ECM increased VEGF, PEDF release, and C3a production in human iPSC-derived RPE cells. This model demonstrates changes seen in the basement membrane can lead to alterations in the cell biology of the RPE cells that may be related to the development of age-related macular degeneration.
C1 [Fields, Mark A.; Gong, Jie; Cai, Hui; Del Priore, Lucian V.] Yale Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT 06510 USA.
   [Bowrey, Hannah E.] Rutgers State Univ, Brain Hlth Inst, Piscataway, NJ USA.
   [Bowrey, Hannah E.] Univ Sydney, Save Sight Inst, Sydney, NSW, Australia.
   [Moreira, Ernesto F.] Med Univ South Carolina, Dept Ophthalmol, Storm Eye Inst, Charleston, SC USA.
C3 Yale University; Rutgers State University New Brunswick; University of
   Sydney; Medical University of South Carolina
RP Fields, MA (通讯作者)，Yale Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT 06510 USA.
EM mark.fields@yale.edu
OI Bowrey, Hannah/0000-0002-3774-4201
FU Research to Prevent Blindness; Greater New York Center for Retinal
   Degenerative Disease Foundation Fighting Blindness; BrightFocus
   Foundation; Lions International Foundation Research Program
FX Research to Prevent Blindness, www.rpbusa.org. Greater New York Center
   for Retinal Degenerative Disease Foundation Fighting Blindness,
   www.blindness.org. BrightFocus Foundation, www.brightfocus.org. The
   Lions International Foundation Research Program. "The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript."
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 15
PY 2017
VL 12
IS 5
AR e0177763
DI 10.1371/journal.pone.0177763
PG 18
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EV0YN
UT WOS:000401473500042
PM 28505174
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Ziemssen, F
   Feltgen, N
   Holz, FG
   Guthoff, R
   Ringwald, A
   Bertelmann, T
   Wiedon, A
   Korb, C
AF Ziemssen, F.
   Feltgen, N.
   Holz, F. G.
   Guthoff, R.
   Ringwald, A.
   Bertelmann, T.
   Wiedon, A.
   Korb, C.
CA OCEAN Study Grp
TI Demographics of patients receiving Intravitreal anti-VEGF treatment in
   real-world practice: healthcare research data versus randomized
   controlled trials
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE NAMD; DME; RVO; Non-interventional study; Demographic characteristics;
   Anti-VEGF; Epidemiology; Ceiling effect
ID RETINAL VEIN OCCLUSION; MACULAR EDEMA SECONDARY; RISK-FACTORS;
   AFLIBERCEPT INJECTION; RANIBIZUMAB; DEGENERATION; BEVACIZUMAB;
   PREVALENCE; POPULATION; EFFICACY
AB Background: While randomized controlled trials (RCTs) are based on strict inclusion/exclusion criteria, non-interventional studies (NISs) might provide additional information to guide management in patients more representative to the real-world setting. The aim of this study was to compare baseline characteristics of patients receiving intravitreal treatment in the NIS OCEAN with those from published RCTs.
   Methods: The ongoing OCEAN study enrolled patients treated with ranibizumab for neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME) or branch/central retinal vein occlusion (B/CRVO). Baseline patient characteristics were compared by indication within the OCEAN cohort. Furthermore, the characteristics were set in reference to those of published RCTs in the same indications. Confidence intervals (CIs) were calculated and assessed for statistically significant differences as indicated by non-overlapping CIs.
   Results: Patient characteristics in the NIS OCEAN were evaluated for 3,614 patients with nAMD, 1,211 with DME, 204 with BRVO and 121 with CRVO. Between these groups, significant differences in mean age, gender distributions, and mean baseline VA were seen, reflecting known differences between the indications. Compared to the patient characteristics of published RCTs (trials selected by literature search: nAMD: 13 RCTs, DME: 9, RVO: 5), the OCEAN patients' mean age was significantly higher in every indication. The gender distributions across the trials were comparable, with only few differences between OCEAN and the RCTs. Regarding the mean baseline VA, notable differences were found in nAMD and in DME, with VA significantly higher in some RCTs and lower in others.
   Conclusions: The described differences underline the complementarity of NISs and RCTs. OCEAN covers a broader spectrum and more variability of patients than do RCTs. As baseline values may have impact on the treatment response (ceiling effect), there is an ongoing need for research in all patient subgroups. Country-specific assessments of patient populations can better reflect the real-world situation. NISs can deliver insights that RCTs may not, as NISs can include non-typical patients, patients with comorbidities, a broader age spectrum and patients of various disease stages.
C1 [Ziemssen, F.] Eberhard Karls Univ Tuebingen, Ctr Ophthalmol, Schleichstr 12, D-72076 Tubingen, Germany.
   [Feltgen, N.] Univ Eye Hosp Goettingen, Gottingen, Germany.
   [Holz, F. G.] Univ Bonn, Dept Ophthalmol, Bonn, Germany.
   [Guthoff, R.] Heinrich Heine Univ Duesseldorf, Univ Eye Hosp, Dusseldorf, Germany.
   [Ringwald, A.] Univ Munster, Klinikum Dortmund, Munster, Germany.
   [Bertelmann, T.] Georg August Univ Goettingen, Dept Ophthalmol, Nurnberg, Germany.
   [Bertelmann, T.] Georg August Univ Goettingen, Novartis Pharma GmbH, Nurnberg, Germany.
   [Wiedon, A.] Novartis Pharma GmbH, Nurnberg, Germany.
   [Korb, C.] Univ Med Ctr Mainz, Dept Ophthalmol, Mainz, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; University of Bonn; Heinrich Heine University Dusseldorf;
   Klinikum Dortmund; University of Munster; Novartis; Novartis; Johannes
   Gutenberg University of Mainz
RP Ziemssen, F (通讯作者)，Eberhard Karls Univ Tuebingen, Ctr Ophthalmol, Schleichstr 12, D-72076 Tubingen, Germany.
EM focke.ziemssen@med.uni-tuebingen.de
RI Ziemssen, Focke/AAY-1686-2021; , Ziemssen/B-9564-2009
OI , Ziemssen/0000-0002-3873-0581
FU Novartis Pharma GmbH (Nuremberg, Germany); Novartis Pharma GmbH
FX The non-interventional OCEAN study was sponsored by Novartis Pharma GmbH
   (Nuremberg, Germany). Medical writing assistance for the preparation of
   this manuscript was also funded by Novartis Pharma GmbH.
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NR 54
TC 43
Z9 43
U1 0
U2 3
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD JAN 19
PY 2017
VL 17
AR 7
DI 10.1186/s12886-017-0401-y
PG 20
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EI0GM
UT WOS:000392151100001
PM 28103831
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Saldanha, IJ
   Dickersin, K
   Wang, X
   Li, TJ
AF Saldanha, Ian J.
   Dickersin, Kay
   Wang, Xue
   Li, Tianjing
TI Outcomes in Cochrane Systematic Reviews Addressing Four Common Eye
   Conditions: An Evaluation of Completeness and Comparability
SO PLOS ONE
LA English
DT Article
ID RANDOMIZED-TRIALS; CLINICAL-TRIALS; REPORTING BIAS; QUALITY; IMPACT
AB Introduction: Choice of outcomes is critical for clinical trialists and systematic reviewers. It is currently unclear how systematic reviewers choose and pre-specify outcomes for systematic reviews. Our objective was to assess the completeness of pre-specification and comparability of outcomes in all Cochrane reviews addressing four common eye conditions.
   Methods: We examined protocols for all Cochrane reviews as of June 2013 that addressed glaucoma, cataract, age-related macular degeneration (AMD), and diabetic retinopathy (DR). We assessed completeness and comparability for each outcome that was named in >= 25% of protocols on those topics. We defined a completely-specified outcome as including information about five elements: domain, specific measurement, specific metric, method of aggregation, and time-points. For each domain, we assessed comparability in how individual elements were specified across protocols.
   Results: We identified 57 protocols addressing glaucoma (22), cataract (16), AMD (15), and DR (4). We assessed completeness and comparability for five outcome domains: quality-of-life, visual acuity, intraocular pressure, disease progression, and contrast sensitivity. Overall, these five outcome domains appeared 145 times (instances). Only 15/145 instances (10.3%) were completely specified (all five elements) (median = three elements per outcome). Primary outcomes were more completely specified than non-primary (median = four versus two elements). Quality-of-life was least completely specified (median = one element). Due to largely incomplete outcome pre-specification, conclusive assessment of comparability in outcome usage across the various protocols per condition was not possible.
   Discussion: Outcome pre-specification was largely incomplete; we encourage systematic reviewers to consider all five elements. This will indicate the importance of complete specification to clinical trialists, on whose work systematic reviewers depend, and will indirectly encourage comparable outcome choice to reviewers undertaking related research questions. Complete pre-specification could improve efficiency and reduce bias in data abstraction and analysis during a systematic review. Ultimately, more completely specified and comparable outcomes could make systematic reviews more useful to decision-makers.
C1 [Saldanha, Ian J.; Dickersin, Kay; Wang, Xue; Li, Tianjing] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins Bloomberg School of Public
   Health
RP Saldanha, IJ (通讯作者)，Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
EM isaldan1@jhmi.edu
OI Wang, Xue/0000-0002-7436-8233
FU National Eye Institute [1U01EY020522]; NATIONAL EYE INSTITUTE
   [U01EY020522] Funding Source: NIH RePORTER
FX This project was funded by the National Eye Institute, grant number
   1U01EY020522 (http://www.nei.nih.gov/). The funder had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 38
TC 69
Z9 70
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 16
PY 2014
VL 9
IS 10
AR e109400
DI 10.1371/journal.pone.0109400
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AQ9XC
UT WOS:000343210800023
PM 25329377
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Lin, T
   Walker, GB
   Kurji, K
   Fang, E
   Law, G
   Prasade, SS
   Kojic, L
   Cao, S
   White, V
   Cui, JZ
   Matsubara, JA
AF Lin, Tony
   Walker, Gregory Brett
   Kurji, Khaliq
   Fang, Edward
   Law, Geoffrey
   Prasade, Shiv S.
   Kojic, Luba
   Cao, Sijia
   White, Valerie
   Cui, Jing Z.
   Matsubara, Joanne A.
TI Parainflammation associated with advanced glycation endproduct
   stimulation of RPE in vitro: Implications for age-related degenerative
   diseases of the eye
SO CYTOKINE
LA English
DT Article
DE Microarray; Age-related macular degeneration; Vitreous; Pathway
   analysis; CXCL11
ID COMPLEMENT FACTOR-H; PIGMENTED EPITHELIAL-CELLS; NF-KAPPA-B;
   END-PRODUCTS; MACULAR DEGENERATION; GENE-EXPRESSION; RECEPTOR;
   ATHEROSCLEROSIS; INFLAMMATION; BIOMARKERS
AB Age related macular degeneration (AMD) is one of the leading causes of blindness in Western society. A hallmark of early stage AMD are drusen, extracellular deposits that accumulate in the outer retina. Advanced glycation endproducts (AGE) accumulate with aging and are linked to several age-related diseases such as Alzheimer's disease, osteoarthritis, atherosclerosis and AMD. AGE deposits are found in drusen and in Bruch's membrane of the eye and several studies have suggested its role in promoting oxidative stress, apoptosis and lipofuscin accumulation. Recently, complement activation and chronic inflammation have been implicated in the pathogenesis of AMD. While AGEs have been shown to promote inflammation in other diseases, whether it plays a similar role in AMD is not known. This study investigates the effects of AGE stimulation on pro- and anti-inflammatory pathways in primary culture of human retinal pigment epithelial cells (RPE). Differential gene expression studies revealed a total of 41 up- and 18 down-regulated RPE genes in response to AGE stimulation. These genes fell into three categories as assessed by gene set enrichment analysis (GSEA). The main categories were inflammation (interferon-induced, immune response) and proteasome degradation, followed by caspase signaling. Using suspension array technology, protein levels of secreted cytokines and growth factors were also examined. Anti-inflammatory cytokines including IL10, 'Lira and IL9 were all overexpressed. Proinflammatory cytokines including IL4, ILI 5 and IFN-gamma were overexpressed, while other pro-inflammatory cytokines including IL8, MCP1, IP10 were underexpressed after AGE stimulation, suggesting a parainflammation state of the RPE under these conditions. Levels of mRNA of chemokine, CXCL11, and viperin, RSAD2, were up-regulated and may play a role in driving the inflammatory response via the NF-kB and JAK-STAT pathways. CXCLI 1 was strongly immunoreactive and associated with drusen in the AMD eye. The pathways and novel genes identified here highlight inflammation as a key response to AGE stimulation in primary culture of human RPE, and identify chemokine CXCL11 as putative novel agent associated with the pathogenesis of AMD. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Lin, Tony] Univ Western Ontario, Fac Med, Dept Ophthalmol, London, ON, Canada.
   [Fang, Edward; Law, Geoffrey; Kojic, Luba; Cao, Sijia; White, Valerie; Cui, Jing Z.; Matsubara, Joanne A.] Univ British Columbia, Dept Ophthalmol & Visual Sci, Fac Med, Vancouver, BC V5Z 3N9, Canada.
   [Walker, Gregory Brett] Univ British Columbia, Dept Internal Med, Fac Med, Vancouver, BC V5Z 3N9, Canada.
   [Kurji, Khaliq] Univ Saskatchewan, Coll Med, Saskatoon, SK S7N 0W0, Canada.
   [Prasade, Shiv S.] Hlth Canada, Biol & Genet Therapies Directorate, Genom Sect, Ottawa, ON K1A 0L2, Canada.
C3 Western University (University of Western Ontario); University of
   British Columbia; University of British Columbia; University of
   Saskatchewan; Health Canada
RP Matsubara, JA (通讯作者)，Univ British Columbia, Dept Ophthalmol & Visual Sci, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada.
EM jms@mail.ubc.ca
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NR 66
TC 39
Z9 40
U1 0
U2 23
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD JUN
PY 2013
VL 62
IS 3
BP 369
EP 381
DI 10.1016/j.cyto.2013.03.027
PG 13
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 160US
UT WOS:000320146600004
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Kose, C
   Sevik, U
   Ikibas, C
   Erdol, H
AF Kose, Cemal
   Sevik, Ugur
   Ikibas, Cevat
   Erdol, Hidayet
TI Simple methods for segmentation and measurement of diabetic retinopathy
   lesions in retinal fundus images
SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
LA English
DT Article
DE Automatic diagnosis of DR; Automatic segmentation; Background image
   extraction; DR; Medical image analysis; Optic disc; Retinal images
ID BLOOD-VESSEL DETECTION; OPTIC DISC; AUTOMATED SEGMENTATION; MACULAR
   DEGENERATION; DIAGNOSIS; PHOTOGRAPHS; DRUSEN
AB Diabetic retinopathy (DR) is one of the most important complications of diabetes mellitus, which causes serious damages in the retina, consequently visual loss and sometimes blindness if necessary medical treatment is not applied on time. One of the difficulties in this illness is that the patient with diabetes mellitus requires a continuous screening for early detection. So far, numerous methods have been proposed by researchers to automate the detection process of DR in retinal fundus images. In this paper, we developed an alternative simple approach to detect DR. This method was built on the inverse segmentation method, which we suggested before to detect Age Related Macular Degeneration (ARMDs). Background image approach along with inverse segmentation is employed to measure and follow up the degenerations in retinal fundus images. Direct segmentation techniques generate unsatisfactory results in some cases. This is because of the fact that the texture of unhealthy areas such as DR is not homogenous. The inverse method is proposed to exploit the homogeneity of healthy areas rather than dealing with varying structure of unhealthy areas for segmenting bright lesions (hard exudates and cotton wool spots). On the other hand, the background image, dividing the retinal image into high and low intensity areas, is exploited in segmentation of hard exudates and cotton wool spots, and microaneurysms (MAs) and hemorrhages (HEMs), separately. Therefore, a complete segmentation system is developed for segmenting DR, including hard exudates, cotton wool spots, MAs, and HEMS. This application is able to measure total changes across the whole retinal image. Hence, retinal images that belong to the same patients are examined in order to monitor the trend of the illness. To make a comparison with other methods, a Naive Bayes method is applied for segmentation of DR. The performance of the system, tested on different data sets including various qualities of retinal fundus images, is over 95% in detection of the optic disc (OD), and 90% in segmentation of the DR. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Kose, Cemal; Ikibas, Cevat] Karadeniz Tech Univ, Fac Engn, Dept Comp Engn, TR-61080 Trabzon, Turkey.
   [Sevik, Ugur] Karadeniz Tech Univ, Fac Arts & Sci, Dept Stat & Comp Sci, TR-61080 Trabzon, Turkey.
   [Erdol, Hidayet] Karadeniz Tech Univ, Fac Med, Dept Ophthalmol, TR-61080 Trabzon, Turkey.
C3 Karadeniz Technical University; Karadeniz Technical University;
   Karadeniz Technical University
RP Kose, C (通讯作者)，Karadeniz Tech Univ, Fac Engn, Dept Comp Engn, TR-61080 Trabzon, Turkey.
EM ckose@ktu.edu.tr; usevik@ktu.edu.tr; cikibas@ktu.edu.tr;
   herdol@ktu.edu.tr
RI ERDÖL, HIDAYET/V-2919-2019; KÖSE, Cemal/V-9731-2017; Şevik,
   Uğur/E-5056-2013
OI ERDÖL, HIDAYET/0000-0003-3176-230X; KÖSE, Cemal/0000-0002-5982-4771;
   Şevik, Uğur/0000-0002-2056-9988; Ikibas, Cevat/0000-0001-9298-7057
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NR 51
TC 44
Z9 46
U1 0
U2 39
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0169-2607
EI 1872-7565
J9 COMPUT METH PROG BIO
JI Comput. Meth. Programs Biomed.
PD AUG
PY 2012
VL 107
IS 2
BP 274
EP 293
DI 10.1016/j.cmpb.2011.06.007
PG 20
WC Computer Science, Interdisciplinary Applications; Computer Science,
   Theory & Methods; Engineering, Biomedical; Medical Informatics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Medical Informatics
GA 970RB
UT WOS:000306148900015
PM 21757250
DA 2022-11-30
ER

PT J
AU Connolly, EE
   Beatty, S
   Thurnham, DI
   Loughman, J
   Howard, AN
   Stack, J
   Nolan, JM
AF Connolly, Eithne E.
   Beatty, Stephen
   Thurnham, David I.
   Loughman, James
   Howard, Alan N.
   Stack, Jim
   Nolan, John M.
TI Augmentation of Macular Pigment Following Supplementation with All Three
   Macular Carotenoids: An Exploratory Study
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Lutein; Macular pigment;
   Meso-zeaxanthin; Supplementation
ID AGE-RELATED MACULOPATHY; OPTICAL-DENSITY; LUTEIN SUPPLEMENTATION; SERUM
   CONCENTRATIONS; PRIMATE RETINAS; SPATIAL PROFILE; MESO-ZEAXANTHIN; HUMAN
   EYE; FLICKER PHOTOMETRY; DEGENERATION
AB Purpose: At the macula, the carotenoids meso-zeaxanthin (MZ), lutein (L), and zeaxanthin (Z) are collectively referred to as macular pigment (MP). This study was designed to measure serum and macular responses to a macular carotenoid formulation.
   Materials and Methods: Ten subjects were recruited into this study (five normal and five with early age-related macular degeneration [AMD]). Subjects were instructed to consume a formulation containing 7.3 mg of MZ, 3.7 mg of L, and 0.8 mg of Z everyday over an eight-week period. The spatial profile of MP optical density (i.e., MPOD at 0.25 degrees, 0.5 degrees, 1 degrees, and 1.75 degrees) was measured using customized heterochromatic flicker photometry, and a blood sample was collected at each study visit in order to analyze serum concentrations of MZ, L, and Z.
   Results: There was a significant increase in serum concentrations of MZ and L after two weeks of supplementation (p < 0.05). Baseline serum carotenoid analysis detected a small peak eluting at the same time as MZ in all subjects, with a mean +/- SD of 0.02 +/- 0.01 mu mol/L. We report significant increases in MPOD at 0.25 degrees, 0.5 degrees, 1 degrees, and average MPOD across its spatial profile after just two weeks of supplementation (p < 0.05, for all). Four subjects (one normal and three AMD) who had an atypical MPOD spatial profile (i.e., central dip) at baseline had the more typical MPOD spatial profile (i. e., highest MPOD at the center) after eight weeks of supplementation.
   Conclusion: We report significant increases in serum concentrations of MZ and L following supplementation with MZ, L, and Z and a significant increase in MPOD, including its spatial profile, after two weeks of supplementation. Also, this study has detected the possible presence of MZ in human serum pre-supplementation and the ability of the study carotenoid formulation to rebuild central MPOD in subjects who have atypical profiles at baseline.
C1 [Connolly, Eithne E.; Beatty, Stephen; Nolan, John M.] Waterford Inst Technol, Dept Chem & Life Sci, Macular Pigment Res Grp, Waterford, Ireland.
   [Connolly, Eithne E.; Beatty, Stephen; Stack, Jim; Nolan, John M.] Inst Vis Res, Whitfield Clin, Waterford, Ireland.
   [Thurnham, David I.] Univ Ulster, No Ireland Ctr Food & Hlth NICHE, Coleraine BT52 1SA, Londonderry, North Ireland.
   [Loughman, James] Dublin Inst Technol, Dept Optometry, Sch Phys, Dublin, Ireland.
   [Howard, Alan N.] Univ Cambridge Downing Coll, Cambridge CB2 1DQ, England.
   [Howard, Alan N.] Howard Fdn, Cambridge, England.
C3 South East Technological University (SETU); Ulster University;
   Technological University Dublin; University of Cambridge
RP Connolly, EE (通讯作者)，Waterford Inst Technol, Dept Chem & Life Sci, Macular Pigment Res Grp, Cork Rd, Waterford, Ireland.
EM econnolly@wit.ie
RI ; Nolan, John/N-4921-2014
OI Loughman, James/0000-0003-3130-8991; Nolan, John/0000-0002-5503-7084
FU Howard Foundation, Cambridge, United Kingdom; Howard Foundation
FX This study was supported by a grant from The Howard Foundation,
   Cambridge, CB22 5LA, United Kingdom. We thank Mr. Jonathon Oates, Head
   of Pharmacy, Waterford Regional Hospital, Dunmore Road, Waterford,
   Ireland, for his help in labeling and packaging the study capsules. Alan
   N. Howard is a trustee of the Howard Foundation, UK charity number
   285822, and as such receives no remuneration from the Foundation. David
   I. Thurnham is a consultant to the Howard Foundation and receives
   consulting fees.
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NR 55
TC 74
Z9 78
U1 1
U2 13
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD APR
PY 2010
VL 35
IS 4
BP 335
EP 351
DI 10.3109/02713680903521951
PG 17
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 663MU
UT WOS:000282892800010
PM 20373901
OA Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Mehta, J
   Farnell, DJJ
   Stappler, T
   Liazos, E
   Wong, D
AF Mehta, Jignasa
   Farnell, Damian J. J.
   Stappler, Theodore
   Liazos, Efstathios
   Wong, David
TI Perception of tilt following counter-rotation surgery
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE adaptation; age-related macular degeneration; counter-rotation surgery;
   tilt
ID MACULAR TRANSLOCATION SURGERY; 360-DEGREES RETINOTOMY; DEGENERATION;
   ADAPTATION; CYCLOTORSION; MANAGEMENT; TORSION; VISION; GLOBE
AB P>Background:
   Macular translocation surgery (MTS) is one of the treatment options for age-related macular degeneration (AMD) followed by counter-rotation surgery (CRS) to correct the resulting tilt. The objective of this paper is to determine the perception of tilt following CRS and identify factors that influence the perception of tilt in the presence of residual cyclorotation following CRS.
   Methods:
   Thirty-four AMD patients treated with MTS and CRS were investigated; and all measurements were made preoperatively, and after each surgical procedure. Fundus photographs were analysed with computer software to determine the degree of retinal rotation and reliability was assessed by two independent assessors. The degree of perceptual rotation was measured with Maddox rod and the subjective appreciation of tilt was established by direct questioning. Fixation preference was determined by cover test and convergence. Bagolini glasses were used to determine binocular outcome.
   Results:
   Post CRS, 20 of the 34 patients had adapted to tilt. There was a significant difference of 5 degrees +/- 7 degrees (95% confidence intervals: 1-8 degrees, t = 2.9, degree of freedom = 19, P = 0.008) between the degree of rotation measured from the fundus photographs and the Maddox rod measurement following CRS. Patients with residual retinal rotation less than or equal to 15 degrees did not appreciate tilt in free space. More importantly, fixation with the operated eye and ignoring the image from the non-operated eye was significantly associated with being free of tilt in natural viewing conditions (P < 0.05).
   Conclusion:
   Despite the presence of residual cyclorotation of the macula following CRS of up to 27 degrees, a significant proportion (59%) of patients did not perceive the world as tilted in natural viewing conditions. Differences between retinal rotation and perceptual tilt provide evidence of sensory adaptation. It was patients who fixed with their operated eye and ignored the image from the non-operated eye who did not perceive tilt post CRS.
C1 [Farnell, Damian J. J.] Univ Manchester, Christie NHS Fdn Trust, Sch Med, Acad Dept Radiat Oncol, Manchester, Lancs, England.
   [Stappler, Theodore; Liazos, Efstathios; Wong, David] Royal Liverpool Univ Hosp, St Pauls Eye Unit, Liverpool, Merseyside, England.
   [Wong, David] Univ Hong Kong, Li Ka Shing Fac Med, Inst Eye, Hong Kong, Hong Kong, Peoples R China.
   [Mehta, Jignasa] Univ Liverpool, Directorate Orthopt & Vis Sci, Manchester, Lancs, England.
C3 Christie NHS Foundation Trust; University of Manchester; Royal Liverpool
   & Broadgreen University Hospitals NHS Trust; Royal Liverpool University
   Hospital; University of Liverpool; University of Hong Kong; University
   of Liverpool
RP Mehta, J (通讯作者)，Univ Liverpool, Directorate Orthopt & Vis Sci, Thompson Yates Bldg, Liverpool L69 3GB, Merseyside, England.
EM jigs@liv.ac.uk
RI Wong, Sai Hung David/D-8482-2015
OI Farnell, Damian/0000-0003-0662-1927; Mehta, Jignasa/0000-0003-1966-4459
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NR 28
TC 1
Z9 1
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1442-6404
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD APR
PY 2010
VL 38
IS 3
BP 284
EP 291
DI 10.1111/j.1442-9071.2010.02235.x
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 586XQ
UT WOS:000276949000011
PM 20447125
DA 2022-11-30
ER

PT J
AU Sallo, FB
   Bereczki, E
   Csont, T
   Luthert, PJ
   Munro, P
   Ferdinandy, P
   Santha, M
   Lengyel, I
AF Sallo, Ferenc B.
   Bereczki, Erika
   Csont, Tamas
   Luthert, Philip J.
   Munro, Peter
   Ferdinandy, Peter
   Santha, Miklos
   Lengyel, Imre
TI Bruch's membrane changes in transgenic mice overexpressing the human
   biglycan and apolipoprotein b-100 genes
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retina; Bruch's membrane; lipids; lipoproteins; proteoglycans; electron
   microscopy; age-related macular degeneration; pigment epithelium of the
   eye
ID RETINAL-PIGMENT EPITHELIUM; AGE-RELATED-CHANGES; HIGH-FAT DIET;
   ULTRASTRUCTURAL-CHANGES; MORPHOMETRIC-ANALYSIS; MACULAR DEGENERATION;
   EXTRACELLULAR-MATRIX; DEPOSIT FORMATION; BASAL DEPOSITS; MOUSE MODEL
AB Age-Related Macular Degeneration (AMD) is characterized by the accumulation of lipid-and protein-rich deposits in Bruch's Membrane (BrM). A consequent decrease in hydraulic conductivity and impairment of transport through BrM may play a central role in the pathogenesis of AMD. The mechanism of deposit formation in AMD had been suggested to show similarities to the formation of atherosclerotic plaques in which the interactions of extracellular matrix proteoglycans with apolipoprotein-B 100 (apoB-100) play an important role. A prime candidate for this interaction is the small leucin-rich proteoglycan biglycan. The aim of our study was to test the effect of the simultaneous overexpression of human apoB-100 and biglycan genes in combination with a high-cholesterol diet on BrM morphology in transgenic mice. Six-weeks-old homozygous apoB-100 or biglycan, hemizygous apoB-100/biglycan transgenic and wild-type C57B1/6 mice were fed either a standard chow or a diet supplemented with 2% cholesterol for 17 weeks. Animals were sacrificed, serum lipid levels were measured and eyes were processed for transmission electron microscopy (TEM) according to standard protocol. Morphometric analysis of digitally acquired TEM images of BrM showed that in apoB-100 and double transgenic animals fed a high-cholesterol diet, the BrM thickness was significantly increased compared to wild-type animals. Both groups had electron-lucent profiles in clusters, scattered throughout the collagenous layers of BrM, and focal nodules of an amorphous material of intermediate electron-density between the plasma and basement membranes of the retinal pigment epithelium (RPE). BrM thickness in these two groups correlated well with elevated cholesterol levels. Unexpectedly, animals overexpressing biglycan alone showed a marked, diet-independent increase in BrM thickness associated with a layer of a basement membrane-like material in outer BrM. The effects of biglycan overexpression are intriguing and further investigations are needed to elucidate the underlying mechanisms. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.
C1 [Sallo, Ferenc B.; Luthert, Philip J.; Munro, Peter; Lengyel, Imre] UCL, Dept Ocular Biol & Therapeut, UCL Inst Ophthalmol, London EC1V 9EL, England.
   [Bereczki, Erika; Santha, Miklos] Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, H-6701 Szeged, Hungary.
   [Csont, Tamas; Ferdinandy, Peter] Univ Szeged, Dept Biochem, Cardiovasc Res Grp, H-6720 Szeged, Hungary.
   [Csont, Tamas; Ferdinandy, Peter] Pharmahungary Grp, H-6722 Szeged, Hungary.
C3 University of London; University College London; Hungarian Academy of
   Sciences; Hungarian Biological Research Center; Szeged University;
   Pharmahungary Group
RP Lengyel, I (通讯作者)，UCL, Dept Ocular Biol & Therapeut, UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
EM i.lengyel@ucl.ac.uk
RI Lengyel, Imre/B-5217-2009; Bereczki, Erika/GSD-4808-2022; Santha,
   Miklos/F-4772-2013; Ferdinandy, Péter/H-9181-2019
OI Lengyel, Imre/0000-0001-7467-2174; Luthert, Philip/0000-0001-7276-6898;
   Bereczki, Erika/0000-0002-0373-7417
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NR 62
TC 23
Z9 24
U1 0
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD AUG
PY 2009
VL 89
IS 2
BP 178
EP 186
DI 10.1016/j.exer.2009.03.006
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 480BQ
UT WOS:000268707200009
PM 19324038
DA 2022-11-30
ER

PT J
AU Bakri, SJ
   Sears, JE
   Lewis, H
AF Bakri, Sophie J.
   Sears, Jonathan E.
   Lewis, Hilel
TI Management of macular hole and submacular hemorrhage in the same eye
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE macular hole; subretinal hemorrhage; tissue plasminogen activator;
   vitrectomy; choroidal neovasculaization; retinl arterial macroaneurysm;
   optical coherence tomography
ID TISSUE-PLASMINOGEN ACTIVATOR; DISPLACEMENT; INJECTION
AB Background: To report the management of patients with a macular hole and submacular hemorrhage in the same eye. Methods: Case reports of two eyes of two patients undergoing pars plana vitrectomy (PPV), subretinal injection of tissue plasminogen activator (t-PA) and airfluid exchange to displace a submacular hemorrhage. In one eye with a submacular hemorrhage due to age-related macular degeneration, a macular hole formed during subretinal t-PA injection. In another patient With a submacular hemorrhage due to a ruptured retinal arterial macroaneurysm (RAM), a sub-internal limiting membrane (ILM) hemorrhage was noted, and a macular hole was found after peeling the ILM, overlying the subretinal hemorrhage. Results: In the first case, after 45 min was allowed for the subretinal clot to liquefy, the macular hole was noted to be closed. A partial air-fluid exchange was performed and the patient was positioned upright, to displace the submacular hemorrhage and tamponade the macular hole. Two weeks later, visual acuity had improved from 20/400 with eccentric viewing to 20/100, the macular hole was closed by optical coherence tomography, and the patient subsequently underwent two sessions of verteporfin photodynamic therapy (PDT) to treat choroidal neovascularization detected by fluorescein angiography. At last follow-up 7 months after surgery, vision was 20/200, the CNV was active angiographically, and another session of PDT was performed. In the second case, PPV was combined with phacoemulsification and intraocular lens implantation. An 80% air-fluid exchange was performed after injecting the subretinal t-PA, the air was exchanged for 14% perfluoropropane gas, and the patient was positioned upright. Visual acuity improved from 20/400 to 20/200 at last follow-up 4 months after surgery, with the RAM spontaneously sclerosed and the macular hole closed clinically and anglographically. Conclusions: Intraoperative evacuation of subretinal hemorrhage is not necessary in cases with coexisting macular hole and submacular hemorrhage. The submacular hemorrhage can be displaced using air or gas, and the bubble can be used to tamponade the macular hole.
C1 Mayo Clin & Mayo Fdn, Dept Ophthalmol, Rochester, MN 55905 USA.
   Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
C3 Mayo Clinic; Cleveland Clinic Foundation
RP Bakri, SJ (通讯作者)，Mayo Clin & Mayo Fdn, Dept Ophthalmol, 200 1st St SW, Rochester, MN 55905 USA.
EM bakri.sophie@mayo.edu
CR Ciardella AP, 2003, AM J OPHTHALMOL, V135, P907, DOI 10.1016/S0002-9394(02)02238-9
   Haupert CL, 2001, AM J OPHTHALMOL, V131, P208, DOI 10.1016/S0002-9394(00)00734-0
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NR 6
TC 9
Z9 9
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD APR
PY 2007
VL 245
IS 4
BP 609
EP 611
DI 10.1007/s00417-006-0349-8
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 163IS
UT WOS:000246153900018
PM 16871381
DA 2022-11-30
ER

PT J
AU Tamada, Y
   Walkup, RD
   Shearer, TR
   Azuma, M
AF Tamada, Yoshiyuki
   Walkup, Ryan D.
   Shearer, Thomas R.
   Azuma, Mitsuyoshi
TI Contribution of calpain to cellular damage in human retinal pigment
   epithelial cells cultured with zinc chelator
SO CURRENT EYE RESEARCH
LA English
DT Article
DE calpain; retinal pigment epithelial cells; SJA6017; alpha-spectrin; zinc
   chelator
ID MACULAR DEGENERATION; RAT RETINA; INHIBITOR; APOPTOSIS; INVOLVEMENT;
   LENS; MACULOPATHY; PROTEOLYSIS; ACTIVATION; CASPASE-3
AB Purpose: We previously showed involvement of calpains in neural retina degeneration induced by hypoxia and ischemia-reperfusion. Age-related macular degeneration (AMD) is one of the leading causes for loss of vision. AMD showed degeneration of neural retina due to dysfunction and degeneration of the retinal pigment epithelium (RPE). RPE performs critical functions in neural retina, such as phagocytosis of shed rod outer segments. The purpose of the current study was to determine the contribution of calpain-induced proteolysis to damage in cultured human RPE cells. Zinc chelator TPEN was used to induce cellular damage as zinc deficiency is a suspected risk factor for AMD. Methods: In RPE/choroid preparations from normal and AMD patients, calpain mRNAs were measured by qPCR, and calpain activity was assessed by casein zymography. Third- to fifth-passage cells from human RPE cells were cultured with TPEN. Cell damage was morphologically assessed under the phase-contrast microscope, and TUNEL staining was performed to detect apoptosis. Leakage of lactate dehydrogenese (LDH) into the medium was measured as a marker of RPE cell damage. Activation of calpains and proteolysis of the known calpain substrate alpha-spectrin were assessed by immunoblotting. To further confirm calpain-induced proteolysis, calpain in homogenized RPE was also activated directly by addition of calcium. Results: RPE/choroid from normal patients expressed mRNAs for calpain 1, calpain 2, and calpastatin moderately, and calpain 2 activity tended to be lower in AMD patients. TPEN caused RPE cell damage with positive TUNEL staining. TPEN also caused leakage of LDH into the medium from RPE cells, and calpain inhibitor SJA6017 inhibited the leakage. Caspase-3 inhibitors z-VAD and z-DEVD also showed inhibitory effects. Immunoblotting for calpain and alpha-spectrin showed activation of calpain in RPE cells cultured with TPEN. Proteolysis by activated calpain was confirmed by addition of calcium to homogenized RPE. Conclusions: These results suggested that activation of calpain contributed to cellular damage induced by TPEN in cultured human RPE cells.
C1 Oregon Grad Inst, Senju Lab Ocular Sci, Beaverton, OR 97006 USA.
   Oregon Hlth & Sci Univ, Dept Integrat Biosci, Portland, OR 97201 USA.
C3 Oregon Health & Science University
RP Azuma, M (通讯作者)，Oregon Grad Inst, Senju Lab Ocular Sci, OHSU W Campus,20000 NW Walker Rd,Suite JM508, Beaverton, OR 97006 USA.
EM mitsuyoshi-azuma@senju.co.jp
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NR 38
TC 8
Z9 8
U1 1
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0271-3683
J9 CURR EYE RES
JI Curr. Eye Res.
PY 2007
VL 32
IS 6
BP 565
EP 573
DI 10.1080/02713680701359633
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 187VL
UT WOS:000247877000009
PM 17612972
DA 2022-11-30
ER

PT J
AU Bains, HS
   Patel, MR
   Singh, H
   Marcus, DM
AF Bains, HS
   Patel, MR
   Singh, H
   Marcus, DM
TI Surgical treatment of extensive peripapillary choroidal
   neovascularization in elderly patients
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID SUB-RETINAL NEOVASCULARIZATION; ARGON-LASER PHOTOCOAGULATION; SUBRETINAL
   NEOVASCULARIZATION; COMPLICATIONS; DETACHMENT
AB Purpose: To report the visual outcomes and complications of surgical removal of extensive peripapillary choroidal neovascularization (PPCNV) in elderly patients.
   Design: Retrospective review.
   Participants: Seventeen consecutive eyes of 17 patients older than age 55 undergoing PPCNV resection.
   Methods: Retrospective review of eyes undergoing surgical removal of extensive PPCNV via pars plana vitrectomy.
   Main Outcome Measures: Preoperative and postoperative Snellen visual acuity.
   Results: The mean age of patients was 76.9 years, and the mean duration of follow-up was 29.8 months. In 6 of 17 eyes, the PPCNV was extrafoveal; in two eyes, it was juxtafoveal; and in nine eyes, it was subfoveal. The cause of CNV was idiopathic (nine eyes), age-related macular degeneration (six eyes), presumed ocular histoplasmosis syndrome (one eye), and inflammation (one eye). All eyes were ineligible for laser treatment by MPS criteria. In eyes with extrafoveal CNV, the preoperative Snellen visual acuity ranged from 20/25 to 20/300, and the final visual acuity ranged from 20/40 to 20/800. The two eyes with juxtafoveal CNV had preoperative visual acuities of 20/125 and 20/300, and both had a postoperative acuity of 20/200. Eyes with subfoveal CNV had a range of preoperative visual acuity from 20/125 to 20/800, whereas the final visual acuity ranged from 20/30 to hand motions. Four of the nine eyes with subfoveal lesions had improved visual acuity. Overall, the final visual acuity was stable or improved in six eyes and worsened in 11 eyes. CNV recurrence was noted in four eyes and required reexcision, laser photocoagulation, or both. Surgical complications included retinal detachment (two eyes), retinal hole and epiretinal membrane (one eye), cystoid macular edema (two eyes), and subsequent cataract extraction (four eyes).
   Conclusions: Surgical removal of extensive PPCNV in the elderly does not often yield improvement or stabilization of visual acuity. However, 6 of 17 patients had stable or improved visual acuity.
C1 Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA.
C3 University System of Georgia; Augusta University
RP Marcus, DM (通讯作者)，Med Coll Georgia, Dept Ophthalmol, 1120 15th St, Augusta, GA 30912 USA.
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NR 26
TC 10
Z9 11
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD AUG
PY 2003
VL 23
IS 4
BP 469
EP 474
DI 10.1097/00006982-200308000-00004
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 718DQ
UT WOS:000185130200004
PM 12972756
DA 2022-11-30
ER

PT J
AU Miskala, PH
   Hawkins, BS
   Mangione, CM
   Bass, EB
   Bressler, NM
   Dong, LM
   Marsh, MJ
   McCaffrey, LD
AF Miskala, PH
   Hawkins, BS
   Mangione, CM
   Bass, EB
   Bressler, NM
   Dong, LM
   Marsh, MJ
   McCaffrey, LD
CA Submacular Surg Trials Res Grp
TI Responsiveness of the National Eye Institute Visual Function
   Questionnaire to changes in visual acuity - Findings in patients with
   subfoveal choroidal neovascularization - SST report no. 1
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID PSYCHOMETRIC PROPERTIES; NEI-VFQ
AB Background: The National Eye Institute Visual Function Questionnaire (NEI-VFQ) measures vision-targeted quality of life, but it is unclear whether it is sensitive to changes within individuals over time.
   Objective: To determine the responsiveness of the NEI-VFQ to "within-individual" changes in visual acuity in patients who had subfoveal choroidal neovascularization in at least one eye secondary to age-related macular degeneration, ocular histoplasmosis syndrome, or idiopathic causes, and who participated in randomized trials of submacular surgery.
   Methods: Trained telephone interviewers administered the NEI-VFQ as part of annual follow-up data collection for pilot trials and larger clinical trials of submacular surgery. Best-corrected visual acuity was measured by local vision examiners at 12 months after enrollment and, typically, by central "traveling" vision examiners at 24 months after enrollment. Changes in visual acuity and NEI-VFQ scores from 12 to 24 months were analyzed using linear regression methods.
   Results: Two-hundrcd eighteen patients had both interviews and visual acuity measurements at 12 and 24 months after enrollment. Changes in the overall NEI-VFQ score and in 9 of the subscales (near activities, dependency, driving, role difficulties, distance activities, mental health, general vision, peripheral vision, and social functioning) were related to changes in visual acuity of the better-seeing eye based on linear regression analysis (P<.05). In our analysis, a 3-line decrease in the visual acuity of the better-seeing eye was associated with 3.6-to 16.2-point decreases in the overall NEI-VFQ score and 9 subscale scores.
   Conclusions: Most of the NEI-VFQ subscales were responsive to changes in the visual acuity of the betterseeing eye over a 12-month interval in this patient population. Thus, the NEI-VFQ can be used to measure change in vision-targeted quality of life over time to augment clinical measurements of visual acuity. Arch Oplithalmol. 2001121:531-539.
C1 Submacular Surg Trials Coordinating Ctr, Baltimore, MD 21205 USA.
RP Hawkins, BS (通讯作者)，Submacular Surg Trials Coordinating Ctr, 550 N Broadway,9th Floor, Baltimore, MD 21205 USA.
OI Folk, James/0000-0002-6271-2906; Bass, Eric/0000-0001-9106-527X
FU NEI NIH HHS [U10 EY011547, U10 EY011557, U10 EY011557-08, U10 EY 11558,
   U10 EY011547-07, U10 EY011558, U10 EY 11557, U10 EY011558-07, U10 EY
   11547] Funding Source: Medline; NATIONAL EYE INSTITUTE [U10EY011547,
   U10EY011557, U10EY011558] Funding Source: NIH RePORTER
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NR 19
TC 97
Z9 98
U1 1
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD APR
PY 2003
VL 121
IS 4
BP 531
EP 539
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 664QM
UT WOS:000182071800012
PM 12695250
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Schmid, A
   Bucher, F
   Liczenczias, E
   Figueroa, SM
   Muller, B
   Agostini, H
AF Schmid, Anke
   Bucher, Felicitas
   Liczenczias, Erika
   Figueroa, Sara Maslanka
   Mueller, Bettina
   Agostini, Hansjuergen
TI nAMD: optimization of patient care and patient-oriented information with
   the help of an internet-based survey
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Survey; Internet-based; Quality of
   Life; SF-12v2; nAMD
ID GROWTH-FACTOR THERAPY; MACULAR DEGENERATION; FOLLOW-UP; RANIBIZUMAB;
   ADHERENCE; TIME; VERTEPORFIN
AB Purpose This survey was conducted to identify factors that influence how patients with neovascular age-related macular degeneration (nAMD) deal with their disease and information that are considered useful from a patient's point of view. Methods A total of 5035 patients with nAMD living in Germany were interviewed via internet-based cross-sectional survey, where the following information was collected: personal data, disease awareness, and patients' needs. In addition, a Quality of Life questionnaire (SF-12v2) could be completed. Results Out of the 5035 participants, more males than females participated (55% vs 45%), and most participants were in the age groups 76 to 85 years (37%) and 66 to 75 years (35%). Seventy-three percent of patients rated their understanding of the disease as at least sufficient, and more than two-thirds of the patients (68%) were aware that their disease needs to be controlled on a regular basis and treated on an "as needed" basis. Regarding potential risk factors for AMD, most participants were aware of age (89%), but only 39% of hereditary load and 33% of smoking as evidence-based risk factors, indicating a need for further information. The doctor remains the major source of information (93%), with internet (29%), brochures (14%), opticians (13%), or patient support groups (4%) with only limited contribution. Distance to the treatment center was identified as one of the factors, which had the greatest influence on patients' compliance. A "treat as needed" regime turned out to be the preferred control and treatment schedule in contrast to a "fixed appointment" every 4 weeks. Conclusion This internet-based survey appears to be representative for nAMD patients. To increase patients' compliance, proximity to the treatment center and a "treat as needed" regime turned out to be important factors as well as patients' awareness of their disease. In this regard, the reported desire for more information indicates that patients' knowledge still needs to be improved. Our results will help to further optimize patient care and patient-oriented information.
C1 [Schmid, Anke; Bucher, Felicitas; Agostini, Hansjuergen] Univ Freiburg, Fac Med, Eye Ctr, Freiburg, Germany.
   [Liczenczias, Erika; Figueroa, Sara Maslanka; Mueller, Bettina] Novartis Pharma GmbH, Nurnberg, Germany.
C3 University of Freiburg; Novartis
RP Agostini, H (通讯作者)，Univ Freiburg, Fac Med, Eye Ctr, Freiburg, Germany.
EM hansjuergen.agostini@uniklinik-freiburg.de
FU Novartis Pharma GmbH; Projekt DEAL
FX Open Access funding enabled and organized by Projekt DEAL. Funding
   provided by Novartis Pharma GmbH.
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NR 30
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD OCT
PY 2022
VL 260
IS 10
BP 3241
EP 3253
DI 10.1007/s00417-022-05678-7
EA MAY 2022
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4O6EP
UT WOS:000795183800001
PM 35552499
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Ren, CD
   Hu, WN
   Wei, QQ
   Cai, WT
   Jin, HZ
   Yu, DH
   Liu, C
   Shen, TY
   Zhu, MJ
   Liang, XW
   Yu, J
AF Ren, Chengda
   Hu, Weinan
   Wei, Qingquan
   Cai, Wenting
   Jin, Huizi
   Yu, Donghui
   Liu, Chang
   Shen, Tianyi
   Zhu, Meijiang
   Liang, Xiuwei
   Yu, Jing
TI MicroRNA-27a Promotes Oxidative-Induced RPE Cell Death through Targeting
   FOXO1
SO BIOMED RESEARCH INTERNATIONAL
LA English
DT Article
ID MACULAR DEGENERATION; STRESS; AUTOPHAGY; ACTIVATION; INJURY; MIRNAS
AB Age-related macular degeneration (AMD) is a multifactor disease, which is primarily characterized by retinal pigment epithelium (RPE) cell loss. Since the retina is the most metabolically active tissue, RPE cells are exposed to consistent oxidative environment. So, oxidation-induced RPE cell death has long been considered a contributor to the onset of AMD. Here, we applied a retinal degeneration (RD) rat model induced by blue light-emitting diode (LED) and a cell model constructed by H2O2 stimulus to mimic the prooxidant environment of the retina. We detected that the expression of miR-27a was upregulated and the expression of FOXO1 was downregulated in both models. So, we furtherly investigated the role of miR-27a-FOXO1 axis in RPE in protesting against oxidants. Lentivirus-mediated RNA was injected intravitreally into rats to modulate the miR-27a-FOXO1 axis. Retinal function and histopathological changes were evaluated by electroretinography (ERG) analysis and hematoxylin and eosin (H&E) staining, respectively. Massive photoreceptor and RPE cell death were examined by terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL). The damage to the retina was aggravated in the FOXO1 gene-knockdown and miR-27a-overexpression groups after exposure to LED but was alleviated in the FOXO1 gene-overexpression or miR-27a-knockdown groups. Dual luciferase assay was used to detect the binding site of miR-27a and FOXO1. Upregulated miR-27a inhibited the expression of FOXO1 by directly binding to the FOXO1 mRNA 3'UTR and decreased the autophagy activity of ARPE-19 cells, resulting in the accumulation of reactive oxygen species (ROS) and decrease of cell viability. The results suggest that miR-27a is a negative regulator of FOXO1. Also, our data emphasize the prominent role of miR-27a/FOXO1 axis in modulating ROS accumulation and cell death in RPE cell model under oxidative stress and influencing the retinal function in the LED-induced RD rat model.
C1 [Ren, Chengda; Wei, Qingquan; Cai, Wenting; Jin, Huizi; Yu, Donghui; Liu, Chang; Shen, Tianyi; Zhu, Meijiang; Yu, Jing] Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Ophthalmol, Shanghai 200072, Peoples R China.
   [Hu, Weinan] Anhui Univ Sci & Technol, Dept Ophthalmol, Huainan 232001, Anhui, Peoples R China.
   [Liang, Xiuwei] Jingdezhen 1 Peoples Hosp, Dept Ophthalmol, Jingdezhen 333000, Jiangxi, Peoples R China.
   [Yu, Jing] Ninghai First Hosp, Dept Ophthalmol, Ningbo 315600, Zhejiang, Peoples R China.
C3 Tongji University; Anhui University of Science & Technology
RP Yu, J (通讯作者)，Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Ophthalmol, Shanghai 200072, Peoples R China.; Liang, XW (通讯作者)，Jingdezhen 1 Peoples Hosp, Dept Ophthalmol, Jingdezhen 333000, Jiangxi, Peoples R China.; Yu, J (通讯作者)，Ninghai First Hosp, Dept Ophthalmol, Ningbo 315600, Zhejiang, Peoples R China.
EM lxw1259268220@163.com; dryujing@aliyun.com
RI Yu, Donghui/HCH-5897-2022
OI Yu, Donghui/0000-0001-5360-6186
FU Fundamental Research Funds for the Central Universities [PA2018001057];
   Public Welfare Technology Funds of Ningbo [2019C50051]
FX This work was supported by the "Fundamental Research Funds for the
   Central Universities" (grant number PA2018001057) and by the "Public
   Welfare Technology Funds of Ningbo" (grant number 2019C50051).
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NR 37
TC 1
Z9 1
U1 1
U2 2
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2314-6133
EI 2314-6141
J9 BIOMED RES INT
JI Biomed Res. Int.
PD NOV 1
PY 2021
VL 2021
AR 6666506
DI 10.1155/2021/6666506
PG 17
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA YN4SX
UT WOS:000747251500003
PM 34761005
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, SB
   Liu, YR
   Liu, Y
   Li, CY
   Wan, Q
   Yang, L
   Su, YR
   Cheng, YQ
   Liu, C
   Wang, XR
   Wang, ZC
AF Wang, Shoubi
   Liu, Yurun
   Liu, Ying
   Li, Chaoyang
   Wan, Qi
   Yang, Liu
   Su, Yaru
   Cheng, Yaqi
   Liu, Chang
   Wang, Xiaoran
   Wang, Zhichong
TI Reversed Senescence of Retinal Pigment Epithelial Cell by Coculture With
   Embryonic Stem Cell via the TGF beta and PI3K Pathways
SO FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE embryonic stem cell; age-related macular degeneration; retinal pigment
   epithelium cell; reversing cellular senescence; regulatory mechanism
ID INDUCED PREMATURE SENESCENCE; OXIDATIVE STRESS; RPE CELLS; DNA-DAMAGE;
   KINASE 1; CYCLE; EXPRESSION; MICROENVIRONMENT; ACTIVATION; APOPTOSIS
AB Retinal pigment epithelium (RPE) cellular senescence is an important etiology of age-related macular degeneration (AMD). Aging interventions based on the application of stem cells to delay cellular senescence have shown good prospects in the treatment of age-related diseases. This study aimed to investigate the potential of the embryonic stem cells (ESCs) to reverse the senescence of RPE cells and to elucidate its regulatory mechanism. The hydrogen peroxide (H2O2)-mediated premature and natural passage-mediated replicative senescent RPE cells were directly cocultured with ESCs. The results showed that the proliferative capacity of premature and replicative senescent RPE cells was increased, while the positive rate of senescence-associated galactosidase (SA-beta-GAL) staining and levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were decreased. The positive regulatory factors of cellular senescence (p53, p21(WAF1/CIP1), p16(INK4a)) were downregulated, while the negative regulatory factors of cellular senescence (Cyclin A2, Cyclin B1, Cyclin D1) were upregulated. Furthermore, replicative senescent RPE cells entered the S and G(2)/M phases from the G(0)/G(1) phase. TGF beta (TGFB1, SMAD3, ID1, ID3) and PI3K (PIK3CG, PDK1, PLK1) pathway-related genes were upregulated in premature and replicative senescent RPE cells after ESCs application, respectively. We further treated ESCs-cocultured premature and replicative senescent RPE cells with SB531542 and LY294002 to inhibit the TGF beta and PI3K pathways, respectively, and found that p53, p21(WAF1/CIP1) and p16(INK4a) were upregulated, while Cyclin A2, Cyclin B1, Cyclin D1, TGF beta, and PI3K pathway-related genes were downregulated, accompanied by decreased proliferation and cell cycle transition and increased positive rates of SA-beta-GAL staining and levels of ROS and MMP. In conclusion, we demonstrated that ESCs can effectively reverse the senescence of premature and replicative senescent RPE cells by a direct coculture way, which may be achieved by upregulating the TGF beta and PI3K pathways, respectively, providing a basis for establishing a new therapeutic option for AMD.
C1 [Wang, Shoubi; Liu, Yurun; Liu, Ying; Li, Chaoyang; Wan, Qi; Yang, Liu; Su, Yaru; Cheng, Yaqi; Liu, Chang; Wang, Xiaoran; Wang, Zhichong] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou, Peoples R China.
C3 Sun Yat Sen University
RP Wang, XR; Wang, ZC (通讯作者)，Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou, Peoples R China.
EM wxran@mail2.sysu.edu.cn; wangzhichong@gzzoc.com
RI Li, Chao/GSM-8117-2022
OI Li, Chao/0000-0001-6110-6210
FU National Key R&D Program of China [2018YFC1106000]
FX This work was supported by the National Key R&D Program of China
   (2018YFC1106000).
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NR 53
TC 8
Z9 8
U1 1
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 2296-634X
J9 FRONT CELL DEV BIOL
JI Front. Cell. Dev. Biol.
PD NOV 26
PY 2020
VL 8
AR 588050
DI 10.3389/fcell.2020.588050
PG 21
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA PD4QZ
UT WOS:000597672500001
PM 33324644
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Leung, EH
   Gibbons, A
   Koch, DD
AF Leung, Ella H.
   Gibbons, Allister
   Koch, Douglas D.
TI Cost-Effectiveness of Preoperative OCT in Cataract Evaluation for
   Multifocal Intraocular Lens
SO OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; SURGERY; DELAY;
   OUTCOMES; EYES; DISSATISFACTION; EXPLANTATION; DISEASE; EDEMA
AB Purpose: To determine the cost effectiveness of an adjunctive screening OCT during the preoperative evaluation of a patient considering cataract surgery with a multifocal intraocular lens (IOL) implantation.
   Design: Cost-effectiveness analysis.
   Participants: A 67-year-old man with 20/60 vision undergoing evaluation for first-eye cataract surgery.
   Methods: The cost-effectiveness analysis of the reference patient undergoing a preoperative cataract examination with and without a screening OCT was performed, evaluating for vitreoretinal diseases including an epiretinal membrane, age-related macular degeneration, vitreomacular traction, and cystoid macular edema. It was assumed that patients with macular pathologies detected before surgery would receive a monofocal IOL and be referred to a retina specialist for evaluation and management. The Medicare reimbursable cost of an OCT was $41.81. All costs and benefits were adjusted for inflation to 2019 United States dollars and discounted 3% per annum over a 16-year time horizon. Probability sensitivity analyses and 1-way deterministic sensitivity analyses were performed to assess for uncertainty.
   Main Outcome Measures: Incremental cost-effectiveness ratio and incremental cost-utility ratio (ICUR) measured in quality-adjusted life years (QALYs).
   Results: Approximately 20.5% of patients undergoing cataract surgery may have macular pathologies, of which 11 % may not be detected on the initial clinical examination. In the base case, an adjunctive preoperative OCT was cost effective from a third-party payer and societal perspective in the United States. In the probability sensitivity analyses, the ICURs were within the societal willingness-to-pay threshold of $50 000/QALY in approximately 64.4% of the clinical scenarios.
   Conclusions: A preoperative screening OCT during the evaluation of a patient considering a multifocal IOL added to the costs of the cataract surgery, but the OCT increased the detection of macular pathologies and improved the QALYs over time. An adjunctive screening OCT can be cost effective from a third-party payer and societal perspective. (C) 2020 by the American Academy of Ophthalmology
C1 [Leung, Ella H.; Koch, Douglas D.] Baylor Coll Med, Cullen Eye Inst, 1977 Butler Blvd, Houston, TX 77030 USA.
   [Gibbons, Allister] Univ Miami, Bascom Palmer Eye Inst, Miami, FL USA.
C3 Baylor College of Medicine; Bascom Palmer Eye Institute; University of
   Miami
RP Leung, EH (通讯作者)，Baylor Coll Med, Cullen Eye Inst, 1977 Butler Blvd, Houston, TX 77030 USA.
EM ehleung@bcm.edu
OI Koch, Douglas/0000-0002-2313-1738
FU National Institutes of Health, Bethesda, Maryland [P30EY014801]; United
   States Department of Defense [W81XWH-13-1-0048]; Research to Prevent
   Blindness, Inc., New York, New York; Sid W. Richardson Foundation
FX Supported by the National Institutes of Health, Bethesda, Maryland (core
   grant no.: P30EY014801); the United States Department of Defense (grant
   no.: W81XWH-13-1-0048); Research to Prevent Blindness, Inc., New York,
   New York (unrestricted grant); and the Sid W. Richardson Foundation
   (unrestricted grant). The sponsor or funding organization had no role in
   the design or conduct of this research.
CR [Anonymous], 2012, AM J OPHTHALMOL, DOI DOI 10.1016/J.AJO.2011.09.013
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NR 40
TC 5
Z9 5
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2020
VL 127
IS 7
BP 859
EP 865
DI 10.1016/j.ophtha.2020.01.049
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ND9OC
UT WOS:000562228700007
PM 32173111
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zhou, RM
   Shi, LJ
   Shan, K
   Sun, YN
   Wang, SS
   Zhang, SJ
   Li, XM
   Jiang, Q
   Yan, B
   Zhao, C
AF Zhou, Rong-mei
   Shi, Lian-jun
   Shan, Kun
   Sun, Ya-nan
   Wang, Shan-shan
   Zhang, Shu-jie
   Li, Xiu-miao
   Jiang, Qin
   Yan, Biao
   Zhao, Chen
TI Circular RNA-ZBTB44 regulates the development of choroidal
   neovascularization
SO THERANOSTICS
LA English
DT Article
DE choroidal neovascularization; circular RNA; cZBTB44; miR-578 sponge
ID MACULAR DEGENERATION; RNAS; INHIBITION; BIOGENESIS
AB Rationale: Choroidal neovascularization (CNV) is a major cause of severe vision loss and occurs in many ocular diseases, especially neovascular age-related macular degeneration (nAMD). Circular RNAs (circRNAs) are emerging as a new class of endogenous noncoding RNAs, which have been implicated in the regulation of endothelial cell dysfunction in diabetes mellitus and cancer. In this study, we aimed to determine the role of circRNA-ZBTB44 (cZBTB44) in the pathogenesis of CNV.
   Methods: Quantitative polymerase chain reaction was conducted to detect cZBTB44 expression pattern during CNV development. Isolectin B4 staining, hematoxylin and eosin (HE) staining, and choroidal sprouting assay ex vivo were conducted to evaluate the role of cZBTB44 in the development of CNV. Endothelial cell proliferation, migration and tube formation assays were conducted to determine the role of cZBTB44 in angiogenic effect in vitro. Bioinformatics analysis, RNA immunoprecipitation assay, luciferase assay, and in vitro studies were conducted to investigate the mechanism of cZBTB44-mediated CNV development.
   Results: cZBTB44 expression was significantly up-regulated in a laser-induced CNV mouse model in vivo and in endothelial cells upon hypoxia stress in vitro. cZBTB44 silencing retarded CNV development, while overexpression of cZBTB44 showed the opposite effects. The role of cZBTB44 in CNV development was confirmed in choroidal sprouting assay ex vivo. cZBTB44 silencing reduced endothelial cell viability, proliferation, migration and tube formation in vitro. cZBTB44 acted as miR-578 sponge to sequester and inhibit miR-578 activity, which led to increased expression of vascular endothelial growth factor A (VEGFA) and vascular cell adhesion molecule-1 (VCAM1). Overexpression of miR-578 mimicked cZBTB44 silencing-mediated anti-angiogenic effects in vivo and in vitro. Furthermore, dysregulated cZBTB44 expression was detected in the clinical samples of nAMD patients.
   Conclusions: This study provided novel insights into the molecular pathogenesis of CNV. The cZBTB44-miR-578-VEGFA/VCAM1 axis might be a potential source of novel therapeutic targets for neovascularization-related diseases.
C1 [Zhou, Rong-mei; Shan, Kun; Sun, Ya-nan; Zhang, Shu-jie; Yan, Biao; Zhao, Chen] Fudan Univ, Eye & ENT Hosp, Shanghai Med Coll, Eye Inst, Shanghai, Peoples R China.
   [Shi, Lian-jun; Li, Xiu-miao; Jiang, Qin] Nanjing Med Univ, Sch Clin Med 4, Nanjing, Peoples R China.
   [Shi, Lian-jun; Li, Xiu-miao; Jiang, Qin] Nanjing Med Univ, Eye Hosp, Nanjing, Peoples R China.
   [Zhang, Shu-jie; Yan, Biao; Zhao, Chen] Fudan Univ, Chinese Acad Med Sci, Key Lab Myopia, NHC Key Lab Myopia, Shanghai, Peoples R China.
   [Zhang, Shu-jie; Yan, Biao; Zhao, Chen] Fudan Univ, Shanghai Key Lab Visual Impairment & Restorat, Shanghai, Peoples R China.
   [Wang, Shan-shan] Nanjing Med Univ, State Key Lab Reprod Med, Affiliated Hosp 1, Dept Ophthalmol, Nanjing, Peoples R China.
   [Zhao, Chen] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China.
C3 Fudan University; Nanjing Medical University; Nanjing Medical
   University; Chinese Academy of Medical Sciences - Peking Union Medical
   College; Fudan University; Fudan University; Nanjing Medical University;
   Sun Yat Sen University
RP Yan, B; Zhao, C (通讯作者)，Fudan Univ Shanghai, Coll Med, Eye & ENT Hosp, Eye Inst, 83 Fenyang Rd, Shanghai 200031, Peoples R China.
EM yanbiao1982@hotmail.com; dr_zhaochen@163.com
FU National Natural Science Foundation of China [81525006, 81670864,
   81730025, 81800851]; Shanghai Outstanding Academic Leaders [2017BR013]
FX This work was supported by National Natural Science Foundation of China
   (81525006, 81670864 and 81730025 to C.Z, 81800851 to RM.Z.); Shanghai
   Outstanding Academic Leaders (2017BR013 to C.Z). The funders have no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.
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   Yang XM, 2009, INVEST OPHTH VIS SCI, V50, P1873, DOI 10.1167/iovs.08-2591
   Zhang Y, 2017, THERANOSTICS, V7, P3155, DOI 10.7150/thno.19646
NR 44
TC 13
Z9 15
U1 0
U2 4
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2020
VL 10
IS 7
BP 3293
EP 3307
DI 10.7150/thno.39488
PG 15
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA KM9HS
UT WOS:000514452800028
PM 32194869
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Rodriguez, JD
   Wallstrom, G
   Narayanan, D
   Welch, D
   Abelson, MB
AF Rodriguez, John D.
   Wallstrom, Garrick
   Narayanan, Divya
   Welch, Donna
   Abelson, Mark B.
TI An Alternative Psychophysical Diagnostic Indicator of the Aging Eye
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PHOTOSTRESS TEST; MACULAR FUNCTION; RETINAL FUNCTION; RECOVERY-TIME;
   DAZZLING TEST; DIABETIC-RETINOPATHY; FLICKER SENSITIVITY; GLARE
   RECOVERY; AGE; LIGHT
AB Purpose. Impaired adaptation to changes in lighting levels as well as mesopic visual function is a common complaint in those over the age of 65. The use of photostress is a well-established method to test the adaption rate and the response of the visual cycle. In this study, we test visual function recovery to mesopic luminance stimuli following a long duration photostress in young and elderly subjects. If successful in strongly differentiating aging macular function, these methods may also be useful in the study of pathologies such as age-related macular degeneration. Methods. A group of 12 older normal subjects (mean age 75.1 +/- 4.79) and a control group of 5 younger normal subjects (mean age 26.2 +/- 4.19) were subjected to macular photostress using the OraLux photostress system. The OraLux system provides a diffuse light source bleaching 84% of cone photopigment while maintaining an exposure safety factor of 200 times less than the maximum safe exposure. After each photostressing session, macular recovery was tracked using a foveal, variable contrast, flickering stimulus of mean luminance in the high mesopic range. Recovery was tracked for 300 seconds. The endpoint was time to recovery to each individual's baseline sensitivity as determined by two static sensitivity trials prior to photostress. Results. Proportional hazards analysis of recovery time yielded a statistically significant difference between the older group and the young group (HR = 0.181; p=0.0289). The estimated hazard ratio of 0.181 indicates that older subjects return to baseline at less than one-fifth the rate of younger subjects. The hazards ratio remained statistically significant after adjusting for visual acuity (HR = 0.093; p=0.0424). Conclusion. Photostress recovery of flicker sensitivity under mesopic conditions is a strong differentiator of aging macular function. This agrees with subject-reported complaints in reduced luminance conditions after exposure to bright lights such as night driving. The qualitative similarity between the aging retina and changes in early AMD suggests that flicker recovery following photostress may be useful as a surrogate endpoint in AMD clinical trials.
C1 [Rodriguez, John D.; Narayanan, Divya; Welch, Donna; Abelson, Mark B.] Ora Inc, Andover, MA 01810 USA.
   [Wallstrom, Garrick] Stat & Data Corp, Tempe, AZ USA.
   [Abelson, Mark B.] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP Rodriguez, JD (通讯作者)，Ora Inc, Andover, MA 01810 USA.
EM jrodriguez@oraclinical.com
FU Ora, Inc.
FX This study was funded by Ora, Inc.
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NR 38
TC 2
Z9 2
U1 0
U2 1
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PD NOV 3
PY 2019
VL 2019
AR 2036192
DI 10.1155/2019/2036192
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JP3VK
UT WOS:000498195000002
PM 31781372
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Le, JT
   Sheng, K
   Saldanha, IJ
   Hawkins, BS
   Li, TJ
AF Le, Jimmy T.
   Sheng, Kai
   Saldanha, Ian J.
   Hawkins, Barbara S.
   Li, Tianjing
TI Outcome Specification in a Sample of Publicly Funded Eye and Vision
   Trials Registered on ClinicalTrials.gov
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID CLINICAL-TRIALS
AB IMPORTANCE For findings from clinical trials to be actionable, outcomes measured in trials must be fully defined and, when appropriate, defined consistently across trials. Otherwise, it is difficult to compare findings between trials, combine results in meta-analyses, or leverage findings collectively to inform health care decision-making.
   OBJECTIVE To identify and characterize outcomes specified in ClinicalTrials.gov records for publicly funded clinical trials for 3 high-burden, high-prevalence eye conditions.
   DESIGN, SETTING, AND PARTICIPANTS ClinicalTrials.gov, a registry of publicly and privately supported clinical studies, was searched on January 31, 2019, for records of clinical trials for age-related macular degeneration (AMD), dry eye, or refractive error. The search was limited to trials funded by the National Eye Institute but did not impose a date restriction. Five elements of a well-specified outcome were extracted from each outcome stated in each record, including the domain, method of measurement, metric, method of aggregation, and time points.
   MAIN OUTCOMES AND MEASURES Number of outcome domains specified for trials for AMD, dry eye, and refractive error and the number of trial records specifying each unique domain.
   RESULTS A total of 49 unique outcome domains specified across 39 records of trials were identified. The median (interquartile range) number of records specifying each unique outcome domain was 1 (1-3), 1.5 (1-2), and 1 (1-1) for AMD, dry eye, and refractive error, respectively. Even when the same domains were registered across multiple trials, the time point, specific metric, and method of aggregation were specified in multiple ways.
   CONCLUSIONS AND RELEVANCE There were too many outcomes with too little overlap in the sample of trials that were examined. Differences in how outcomes are measured across trials make it difficult to compare results, even for well-established domains, such as visual acuity. To reduce this waste in eye and vision research, the time is ripe for agreeing on what outcomes to measure.
C1 [Le, Jimmy T.; Li, Tianjing] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Ctr Clin Trials & Evidence Synth, 615 N Wolfe St,E6140, Baltimore, MD 21205 USA.
   [Sheng, Kai] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
   [Saldanha, Ian J.] Ctr Evidence Synth Hlth, Dept Hlth Serv Policy & Practice, Providence, RI USA.
   [Saldanha, Ian J.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA.
   [Hawkins, Barbara S.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
C3 Johns Hopkins University; Johns Hopkins Bloomberg School of Public
   Health; Harvard University; Harvard T.H. Chan School of Public Health;
   Brown University; Johns Hopkins University; Johns Hopkins Medicine
RP Li, TJ (通讯作者)，Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Ctr Clin Trials & Evidence Synth, 615 N Wolfe St,E6140, Baltimore, MD 21205 USA.
EM tli19@jhu.edu
FU National Institutes of Health [UG1 EY020522]; NATIONAL EYE INSTITUTE
   [UG1EY020522] Funding Source: NIH RePORTER
FX Drs Le, Saldanha, Hawkins, and Li are supported by grant UG1 EY020522
   from the National Institutes of Health.
CR Eden J, 2011, FINDING WHAT WORKS IN HEALTH CARE: STANDARDS FOR SYSTEMATIC REVIEWS, P1
   Gorst SL, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0146444
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NR 8
TC 0
Z9 0
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD NOV
PY 2019
VL 137
IS 11
BP 1292
EP 1294
DI 10.1001/jamaophthalmol.2019.3289
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JW7DV
UT WOS:000503209300013
PM 31465089
OA Green Published
DA 2022-11-30
ER

PT J
AU Kim, J
   Silva, RLE
   Shmueli, RB
   Mirando, AC
   Tzeng, SY
   Pandey, NB
   Ben-Akiva, E
   Popel, AS
   Campochiaro, PA
   Green, JJ
AF Kim, Jayoung
   Lima e Silva, Raquel
   Shmueli, Ron B.
   Mirando, Adam C.
   Tzeng, Stephany Y.
   Pandey, Niranjan B.
   Ben-Akiva, Elana
   Popel, Aleksander S.
   Campochiaro, Peter A.
   Green, Jordan J.
TI Anisotropic poly(lactic-co-glycolic acid) microparticles enable
   sustained release of a peptide for long-term inhibition of ocular
   neovascularization
SO ACTA BIOMATERIALIA
LA English
DT Article
DE Poly(lactic-co-glycolic acid); Microparticle; Anisotropic;
   Anti-angiogenesis; Peptide; Diabetic macular edema; Neovascular
   age-related macular degeneration
ID ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL NEOVASCULARIZATION; ANGIOGENESIS;
   COLLAGEN; PROLIFERATION; DEXAMETHASONE; SUPPRESSION; RETINOPATHY;
   EXPRESSION; PARTICLES
AB Leading causes of vision loss include neovascular age-related macular degeneration (NVAMD) and macular edema (ME), which both require frequent intravitreal injections for treatment. A safe, poly(lactic-co-glycolic acid) (PLGA)-based biodegradable polymeric microparticle (MP) delivery system was developed that encapsulates and protects a biomimetic peptide from degradation, allows sustained intraocular release through polymer hydrolysis, and demonstrates a prolonged anti-angiogenic effect in vivo in three different NVAMD animal models (a laser-induced choroidal neovascularization mouse model, a rhoVEGF transgenic mouse model, and a Tet/opsin/VEGF transgenic mouse model) following intravitreal administration. The role of copolymer composition and microparticle shape was explored and 85:15 lactide-to-glycolide PLGA formed into ellipsoidal microparticles was found to be effective at inhibiting neovascularization for at least 16 weeks in vivo. Treatments were found to not only inhibit the growth of neovascularization, but also to cause regression of the neovasculature, reduce vascular leakage, and prevent exudative retinal detachment. These particulate devices are promising for the sustained release of biologics in the eye and may be useful for treating retinal diseases.
   Statement of Significance
   Devastating retinal diseases cause blindness in millions of people around the world. Current protein based treatments have insufficient efficacy for many patients and also necessitate frequent intravitreal injections. Here, we demonstrate a new treatment consisting of a peptide encapsulated in biodegradable microparticles. We explore the effects of copolymer composition and physical shape of polymeric microparticles and find that both modulate peptide release. Efficacy of the treatment was validated in three different mouse models and the lead formulation was determined to be effective long-term, for at least 16 weeks in vivo, following a single injection. Treatments inhibited and regressed neovascularization as well as reduced vascular leakage. Anisotropic polymeric microparticles are promising for the sustained release of biologics in the eye. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
C1 [Kim, Jayoung; Shmueli, Ron B.; Mirando, Adam C.; Tzeng, Stephany Y.; Pandey, Niranjan B.; Ben-Akiva, Elana; Popel, Aleksander S.; Green, Jordan J.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
   [Kim, Jayoung; Shmueli, Ron B.; Tzeng, Stephany Y.; Ben-Akiva, Elana; Green, Jordan J.] Johns Hopkins Univ, Sch Med, Translat Tissue Engn Ctr, Baltimore, MD 21205 USA.
   [Lima e Silva, Raquel; Campochiaro, Peter A.; Green, Jordan J.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
   [Lima e Silva, Raquel; Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
   [Green, Jordan J.] Johns Hopkins Univ, Inst Nanobiotechnol, Baltimore, MD 21205 USA.
   [Green, Jordan J.] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21205 USA.
   [Green, Jordan J.] Johns Hopkins Univ, Dept Mat Sci & Engn, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins
   University; Johns Hopkins University; Johns Hopkins University; Johns
   Hopkins University; Johns Hopkins University
RP Campochiaro, PA; Green, JJ (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.; Campochiaro, PA; Green, JJ (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
EM pcampo@jhmi.edu; green@jhu.edu
RI Green, Jordan/B-9001-2009
OI Green, Jordan/0000-0003-4176-3808; Popel, Aleksander/0000-0002-6706-9235
FU NIH [R21EY026148, R01EY028996, F32CA210482]; Research to Prevent
   Blindness/Dr. H. James and Carole Free Catalyst Award; Samsung; Wilmer
   Biostatistics Core Grant [EY01765]; NATIONAL CANCER INSTITUTE
   [F32CA210482] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R21EY026148, R01EY028996, P30EY001765] Funding Source: NIH RePORTER
FX The authors thank the NIH for support including R21EY026148,
   R01EY028996, and F32CA210482 (to ACM). The authors also thank the
   Research to Prevent Blindness/Dr. H. James and Carole Free Catalyst
   Award for support. JK thanks Samsung for scholarship support.; The
   authors thank Dr. Jiangxia Wang and the Wilmer Biostatistics Core Grant
   (EY01765) for statistical assistance.
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NR 35
TC 10
Z9 10
U1 0
U2 21
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1742-7061
EI 1878-7568
J9 ACTA BIOMATER
JI Acta Biomater.
PD OCT 1
PY 2019
VL 97
BP 451
EP 460
DI 10.1016/j.actbio.2019.07.054
PG 10
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA JL3ZH
UT WOS:000495470300034
PM 31374338
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Chen, JL
   Hung, CT
   Keller, JJ
   Lin, HC
   Wu, YJ
AF Chen, Jiunn-Liang
   Hung, Chun-Tzu
   Keller, Joseph Jordan
   Lin, Hsien-Chung
   Wu, Yu-Jen
TI Proteomic analysis of retinal pigment epithelium cells after exposure to
   UVA radiation
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Proteomic; UVA; Retinal pigment epithelium cells; Apoptosis;
   Mitochondrial dysfunction
ID ENDOPLASMIC-RETICULUM STRESS; COLLAGEN CROSS-LINKING; MACULAR
   DEGENERATION; OXIDATIVE DAMAGE; ULTRAVIOLET-RADIATION; CARCINOMA CELLS;
   DNA-DAMAGE; BLUE-LIGHT; APOPTOSIS; ACTIVATION
AB Background Age-related macular degeneration (AMD) is the primary cause of blindness and severe vision loss in developed countries and is responsible for 8.7% of blindness globally. Ultraviolet radiation can induce DNA breakdown, produce reactive oxygen species, and has been implicated as a risk factor for AMD. This study investigated the effects of UVA radiation on Human retinal pigment epithelial cell (ARPE-19) growth and protein expression. Methods ARPE-19 cells were irradiated with a UVA lamp at different doses (5, 10, 20, 30 and 40 J/cm(2)) from 10 cm. Cell viability was determined by MTT assay. Visual inspection was first achieved with inverted light microscopy and then the DeadEnd (TM) Fluorometric TUNEL System was used to observe nuclear DNA fragmentation. Flow cytometry based-Annexin V-FITC/PI double-staining was used to further quantify cellular viability. Mitochondrial membrane potential was assessed with JC-1 staining. 2D electrophoresis maps of exposed cells were compared to nonexposed cells and gel images analyzed with PDQuest 2-D Analysis Software. Spots with greater than a 1.5-fold difference were selected for LC-MS/MS analysis and some confirmed by western blot. We further investigated whether caspase activation, apoptotic-related mitochondrial proteins, and regulators of ER stress sensors were involved in UVA-induced apoptosis. Results We detected 29 differentially expressed proteins (9 up-regulated and 20 down-regulated) in the exposed cells. Some of these proteins such as CALR, GRP78, NPM, Hsp27, PDI, ATP synthase subunit alpha, PRDX1, and GAPDH are associated with anti-proliferation, induction of apoptosis, and oxidative-stress protection. We also detected altered protein expression levels among caspases (caspase 3 and 9) and in the mitochondrial (cytosolic cytochrome C, AIF, Mcl-1, Bcl-2, Bcl-xl, Bax, Bad, and p-Bad) and ER stress-related (p-PERK, p-eIF2 alpha, ATF4 and CHOP) apoptotic pathways. Conclusions UVA irradiation suppressed the proliferation of ARPE-19 cells in a dose-dependent manner, caused quantitative loses in transmembrane potential (Delta psi m), and induced both early and late apoptosis.
C1 [Chen, Jiunn-Liang] Kaohsiung Vet Gen Hosp, Dept Ophthalmol, Kaohsiung, Taiwan.
   [Chen, Jiunn-Liang] Natl Yang Ming Univ, Sch Med, Taipei, Taiwan.
   [Chen, Jiunn-Liang] Shu Zen Jr Coll Med & Management, Dept Optometry, Kaohsiung, Taiwan.
   [Hung, Chun-Tzu; Lin, Hsien-Chung] Yuans Gen Hosp, Dept Ophthalmol, Kaohsiung, Taiwan.
   [Keller, Joseph Jordan] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
   [Keller, Joseph Jordan] Taipei Med Univ, Sch Publ Hlth, Coll Publ Hlth, Taipei, Taiwan.
   [Keller, Joseph Jordan] Natl Taipei Univ Nursing & Hlth Sci, Coll Hlth Technol, Int Masters Program, Taipei, Taiwan.
   [Lin, Hsien-Chung] Kaohsiung Med Univ Hosp, Dept Ophthalmol, Kaohsiung, Taiwan.
   [Wu, Yu-Jen] Meiho Univ, Dept Beauty Sci, Pingtung, Taiwan.
C3 Kaohsiung Veterans General Hospital; National Yang Ming Chiao Tung
   University; Ohio State University; Taipei Medical University; National
   Taipei University of Nursing & Health Science (NTUNHS); Kaohsiung
   Medical University; Kaohsiung Medical University Hospital
RP Lin, HC (通讯作者)，Yuans Gen Hosp, Dept Ophthalmol, Kaohsiung, Taiwan.; Wu, YJ (通讯作者)，Meiho Univ, Dept Beauty Sci, Pingtung, Taiwan.
EM m890070@gmail.com; wyr924@ms24.hinet.net
FU Kaohsiung Medical University Hospital [KMU97-7G04]; Yuan General
   Hospital [RG12-002]; National Science Council [NSC
   102-2313-B-276-002-MY3]
FX This study was supported by grants from Kaohsiung Medical University
   Hospital KMU97-7G04 and Yuan General Hospital RG12-002 for Hsien-Chung
   Lin and from National Science Council NSC 102-2313-B-276-002-MY3 for
   Yu-Jen Wu.
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NR 62
TC 7
Z9 8
U1 1
U2 6
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD AUG 2
PY 2019
VL 19
IS 1
AR 168
DI 10.1186/s12886-019-1151-9
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IO2HN
UT WOS:000479203600001
PM 31375076
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Huang, H
   Parlier, R
   Shen, JK
   Lutty, GA
   Vinores, SA
AF Huang, Hu
   Parlier, Rachel
   Shen, Ji-kui
   Lutty, Gerard A.
   Vinores, Stanley A.
TI VEGF Receptor Blockade Markedly Reduces Retinal Microglia/Macrophage
   Infiltration into Laser-Induced CNV
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; INDUCED CHOROIDAL NEOVASCULARIZATION;
   COMPLEMENT FACTOR-H; MACULAR DEGENERATION; MOUSE MODEL; ANGIOGENESIS;
   INHIBITION; MICROGLIA; CELLS; EXPRESSION
AB Although blocking VEGF has a positive effect in wet age-related macular degeneration (AMD), the effect of blocking its receptors remains unclear. This was an investigation of the effect of VEGF receptor (VEGFR) 1 and/or 2 blockade on retinal microglia/macrophage infiltration in laser-induced choroidal neovascularization (CNV), a model of wet AMD. CNV lesions were isolated by laser capture microdissection at 3, 7, and 14 days after laser and analyzed by RT-PCR and immunofluorescence staining for mRNA and protein expression, respectively. Neutralizing antibodies for VEGFR1 or R2 and the microglia inhibitor minocycline were injected intraperitoneally (IP). Anti-CD11b, CD45 and Iba1 antibodies were used to confirm the cell identity of retinal microglia/macrophage, in the RPE/choroidal flat mounts or retinal cross sections. CD11b(+), CD45(+) or Iba1(+) cells were counted. mRNA of VEGFR1 and its three ligands, PlGF, VEGF-A (VEGF) and VEGF-B, were expressed at all stages, but VEGFR2 were detected only in the late stage. PlGF and VEGF proteins were expressed at 3 and 7 days after laser. Anti-VEGFR1 (MF1) delivered IP 3 days after laser inhibited infiltration of leukocyte populations, largely retinal microglia/macrophage to CNV, while anti-VEGFR2 (DC101) had no effect. At 14 days after laser, both MF1 and DC101 antibodies markedly inhibited retinal microglia/macrophage infiltration into CNV. Therefore, VEGFR1 and R2 play differential roles in the pathogenesis of CNV: VEGFR1 plays a dominant role at 3 days after laser; but both receptors play pivotal roles at 14 days after laser. In vivo imaging demonstrated accumulation of GFP-expressing microglia into CNV in both CX3CR1(gfp/gfp) and CX3CR1(gfp/+) mice. Minocycline treatment caused a significant increase in lectin(+) cells in the subretinal space anterior to CNV and a decrease in dextran-perfused neovessels compared to controls. Targeting the chemoattractant molecules that regulate trafficking of retinal microglia/macrophage appears to be a compelling therapeutic strategy to control CNV and treat wet AMD.
C1 [Huang, Hu; Parlier, Rachel; Shen, Ji-kui; Lutty, Gerard A.; Vinores, Stanley A.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Huang, H (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
EM hhuang27@jhmi.edu
FU National Institutes of Health [RO1-EY017164, RO1-EY016557, EY001765];
   research to Prevent Blindness; Lilly/ImClone; NATIONAL EYE INSTITUTE
   [P30EY001765, R01EY016151, R01EY017164] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
   [P30DK079637] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health grants RO1-EY017164 (to SAV
   and GAL), RO1-EY016557 (to GAL), EY001765 (to Wilmer), Unrestricted
   funds from research to Prevent Blindness (to Wilmer), and a stipend from
   Lilly/ImClone. The authors also thank the Raab Family Foundation and the
   Wilmer Pooled Professors Fund for the purchase of the Micron III. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
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NR 51
TC 49
Z9 51
U1 0
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 20
PY 2013
VL 8
IS 8
AR e71808
DI 10.1371/journal.pone.0071808
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 219RU
UT WOS:000324527300039
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Njie-Mbye, YF
   Kulkarni-Chitnis, M
   Opere, CA
   Barrett, A
   Ohia, SE
AF Njie-Mbye, Ya Fatou
   Kulkarni-Chitnis, Madhura
   Opere, Catherine A.
   Barrett, Aaron
   Ohia, Sunny E.
TI Lipid peroxidation: pathophysiological and pharmacological implications
   in the eye
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Review
DE lipid peroxidation; oxidative stress; peroxides; ocular diseases
ID AGE-RELATED-CHANGES; POLYUNSATURATED FATTY-ACIDS; INDUCED-OXIDATIVE
   STRESS; OPEN-ANGLE GLAUCOMA; HYDROGEN-PEROXIDE; MACULAR DEGENERATION;
   TRABECULAR MESHWORK; AQUEOUS-HUMOR; NITRIC-OXIDE; SYMPATHETIC
   NEUROTRANSMISSION
AB Oxygen-derived free radicals such as hydroxyl and hydroperoxyl species have been shown to oxidize phospholipids and other membrane lipid components leading to lipid peroxidation. In the eye, lipid peroxidation has been reported to play an important role in degenerative ocular diseases (age-related macular degeneration, cataract, glaucoma, diabetic retinopathy). Indeed, ocular tissues are prone to damage from reactive oxygen species due to stress from constant exposure of the eye to sunlight, atmospheric oxygen and environmental chemicals. Furthermore, free radical catalyzed peroxidation of long chain polyunsaturated acids (LCPUFAs) such as arachidonic acid and docosahexaenoic acid leads to generation of LCPUFA metabolites including isoprostanes and neuroprostanes that may further exert pharmacological/toxicological actions in ocular tissues. Evidence from literature supports the presence of endogenous defense mechanisms against reactive oxygen species in the eye, thereby presenting new avenues for the prevention and treatment of ocular degeneration. Hydrogen peroxide (H2O2) and synthetic peroxides can exert pharmacological and toxicological effects on tissues of the anterior uvea of several mammalian species. There is evidence suggesting that the retina, especially retinal ganglion cells can exhibit unique characteristics of antioxidant defense mechanisms. In the posterior segment of the eye, H2O2 and synthetic peroxides produce an inhibitory action on glutamate release (using [H-3]-D-aspartate as a marker), in vitro and on the endogenous glutamate and glycine concentrations in vivo. In addition to peroxides, isoprostanes can elicit both excitatory and inhibitory effects on norepinephrine (NE) release from sympathetic nerves in isolated mammalian iris ciliary bodies. Whereas isoprostanes attenuate dopamine release from mammalian neural retina, in vitro, these novel arachidonic acid metabolites exhibit a biphasic regulatory effect on glutamate release from retina and can regulate amino acid neurotransmitter metabolism without inducing cell death in the retina. Furthermore, there appears to be an inhibitory role for neuroprostanes in the release of excitatory amino acid neurotransmitters in mammalian retina. The ability of peroxides and metabolites of LCPUFA to alter the integrity of neurotransmitter pools provides new potential target sites and pathways for the treatment of degenerative ocular diseases.
C1 [Njie-Mbye, Ya Fatou; Kulkarni-Chitnis, Madhura; Ohia, Sunny E.] Texas So Univ, Dept Pharmaceut Sci, Coll Pharm & Hlth Sci, Houston, TX 77004 USA.
   [Opere, Catherine A.; Barrett, Aaron] Creighton Univ, Sch Pharm & Hlth Profess, Dept Pharm Sci, Omaha, NE 68178 USA.
C3 Texas Southern University; Creighton University
RP Ohia, SE (通讯作者)，Texas So Univ, Dept Pharmaceut Sci, Coll Pharm & Hlth Sci, 3100 Cleburne St, Houston, TX 77004 USA.
EM ohiase@tsu.edu
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NR 124
TC 51
Z9 54
U1 1
U2 16
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PY 2013
VL 4
AR 366
DI 10.3389/fphys.2013.00366
PG 10
WC Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Physiology
GA AX2LA
UT WOS:000346774000358
PM 24379787
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Julien, S
   Biesemeier, A
   Kokkinou, D
   Eibl, O
   Schraermeyer, U
AF Julien, Sylvie
   Biesemeier, Antje
   Kokkinou, Despina
   Eibl, Oliver
   Schraermeyer, Ulrich
TI Zinc Deficiency Leads to Lipofuscin Accumulation in the Retinal Pigment
   Epithelium of Pigmented Rats
SO PLOS ONE
LA English
DT Article
ID SENILE MACULAR DEGENERATION; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; OCULAR
   MELANIN; ORAL ZINC; HUMAN RPE; MELANOSOMES; COPPER; CELLS; EXPRESSION
AB Background: Age-related macular degeneration (AMD) is associated with lipofuscin accumulation whereas the content of melanosomes decreases. Melanosomes are the main storage of zinc in the pigmented tissues. Since the elderly population, as the most affected group for AMD, is prone to zinc deficit, we investigated the chemical and ultrastructural effects of zinc deficiency in pigmented rat eyes after a six-month zinc penury diet.
   Methodology/Principal Findings: Adult Long Evans (LE) rats were investigated. The control animals were fed with a normal alimentation whereas the zinc-deficiency rats (ZD-LE) were fed with a zinc deficient diet for six months. Quantitative Energy Dispersive X-ray (EDX) microanalysis yielded the zinc mole fractions of melanosomes in the retinal pigment epithelium (RPE). The lateral resolution of the analysis was 100 nm. The zinc mole fractions of melanosomes were significantly smaller in the RPE of ZD-LE rats as compared to the LE control rats. Light, fluorescence and electron microscopy, as well as immunohistochemistry were performed. The numbers of lipofuscin granules in the RPE and of infiltrated cells (empty set > 3 mu m) found in the choroid were quantified. The number of lipofuscin granules significantly increased in ZD-LE as compared to control rats. Infiltrated cells bigger than 3 mu m were only detected in the choroid of ZD-LE animals. Moreover, the thickness of the Bruch's membrane of ZD-LE rats varied between 0.4-3 mu m and thin, rangy ED1 positive macrophages were found attached at these sites of Bruch's membrane or even inside it.
   Conclusions/Significance: In pigmented rats, zinc deficiency yielded an accumulation of lipofuscin in the RPE and of large pigmented macrophages in the choroids as well as the appearance of thin, rangy macrophages at Bruch's membrane. Moreover, we showed that a zinc diet reduced the zinc mole fraction of melanosomes in the RPE and modulated the thickness of the Bruch's membrane.
C1 [Julien, Sylvie; Biesemeier, Antje; Kokkinou, Despina; Schraermeyer, Ulrich] Ctr Ophthalmol, Sect Expt Vitreoretinal Surg, Inst Ophthalm Res, Tubingen, Germany.
   [Eibl, Oliver] Univ Tubingen, Inst Appl Phys, Tubingen, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Eberhard Karls University of Tubingen
RP Julien, S (通讯作者)，Ctr Ophthalmol, Sect Expt Vitreoretinal Surg, Inst Ophthalm Res, Tubingen, Germany.
EM Ulrich.Schraermeyer@med.uni-tuebingen.de
OI Biesemeier, Antje/0000-0002-3462-8803; Julien-Schraermeyer,
   Sylvie/0000-0002-2322-511X
FU Deutsche Forschungsgesellschaft DFG SCHR [436/12-2]
FX This work was supported by a grant from the Deutsche
   Forschungsgesellschaft DFG SCHR 436/12-2. The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 56
TC 25
Z9 25
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 22
PY 2011
VL 6
IS 12
AR e29245
DI 10.1371/journal.pone.0029245
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 884DI
UT WOS:000299684700043
PM 22216222
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Vasconcelos-Santos, DV
   Nehemy, PG
   Schachat, AP
   Nehemy, MB
AF Vasconcelos-Santos, Daniel V.
   Nehemy, Patricia G.
   Schachat, Andrew P.
   Nehemy, Marcio B.
TI Secondary ocular hypertension after intravitreal injection of 4 mg of
   triamcinolone acetonide - Incidence and risk factors
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE intravitreal triamcinolone acetonide injection; ocular hypertension;
   risk factors
ID INTRAOCULAR-PRESSURE ELEVATION; TRABECULAR MESHWORK; SUBTENON INJECTION;
   MACULAR EDEMA; GLAUCOMA; COMPLICATIONS; PARACENTESIS; VERTEPORFIN;
   DURATION; THERAPY
AB Purpose: To analyze the incidence of secondary ocular hypertension (SOH) after intravitreal triamcinolone acetonide (IVTA) injection and its risk predictors.
   Methods: Retrospective review of charts for 219 consecutive patients receiving a 4-mg IVTA injection.
   Results: One hundred fifty eyes of 150 patients who were followed for at least 3 months and met inclusion criteria were considered. Main indications for IVTA injection were neovascular age-related macular degeneration (79 eyes [52.7%]), choroidal neovascularization due to other etiologies (22 eyes [14.7%]), diabetic macular edema (14 eyes [9.3%]), central retinal vein occlusion (12 eyes [8.0%]), and branch retinal vein occlusion (8 eyes [5.3%]). SOH defined as intraocular pressure (IOP) of >= 21 mmHg was recorded for 32.0% of injected eyes at some point during a mean follow-up of 7.7 months. There was no association between SOH and age, sex, arterial hypertension, diabetes mellitus, indication for IVTA injection, prior cataract surgery, or concurrent photodynamic therapy. Although previous pars plana vitrectomy did not influence risk, peak IOP was lower in vitrectomized eyes (P = 0.044). Prior diagnosis of glaucoma was a significant risk factor for SOH (relative risk = 2.17; P = 0.004). In nonglaucomatous eyes, baseline IOP of 16 mmHg was associated with a higher risk of SOH (relative risk = 2.31; P = 0.003). Baseline IOPs of <12 mmHg, 12-14 mmHg, 15-17 mmHg, 18-20 mmHg, and >20 mmHg were associated with incidences of SOH of 11.1 %, 25.4%, 40.0%, 46.2%, and 50.0% (P = 0.01), respectively.
   Conclusions: A 4-mg IVTA injection was associated with SOH in 32.0% of treated eyes. The risk of SOH was higher in eyes with previous glaucoma and higher baseline IOP. Peak IOP after IVTA injection was lower in vitrectomized eyes. Risk factor analysis may permit better individualization of the risk-benefit ratio for IVTA injection.
C1 [Vasconcelos-Santos, Daniel V.; Nehemy, Patricia G.; Nehemy, Marcio B.] Univ Fed Minas Gerais, BR-30350100 Belo Horizonte, MG, Brazil.
   [Nehemy, Patricia G.; Nehemy, Marcio B.] Inst Vis, Belo Horizonte, MG, Brazil.
   [Schachat, Andrew P.] Cleveland Clin, Cleveland, OH 44106 USA.
C3 Universidade Federal de Minas Gerais; Cleveland Clinic Foundation
RP Vasconcelos-Santos, DV (通讯作者)，Univ Fed Minas Gerais, Rua Joao Freitas,73-401, BR-30350100 Belo Horizonte, MG, Brazil.
EM dvitor@ufmg.br
RI Vasconcelos-Santos, Daniel V/D-3576-2013; Nehemy, Marcio/ABD-5089-2021
OI Vasconcelos-Santos, Daniel V/0000-0002-6747-2024; Nehemy,
   Marcio/0000-0002-4104-0346
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NR 53
TC 52
Z9 55
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD APR
PY 2008
VL 28
IS 4
BP 573
EP 580
DI 10.1097/IAE.0b013e31816079e8
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 293YH
UT WOS:000255370800008
PM 18398360
DA 2022-11-30
ER

PT J
AU Fawcett, RJ
   Osborne, NN
AF Fawcett, R. J.
   Osborne, N. N.
TI Flupirtine attenuates sodium nitroprusside-induced damage to retinal
   photoreceptors, in situ
SO BRAIN RESEARCH BULLETIN
LA English
DT Article
DE flupirtine; antioxidant; nitric oxide; retinal photoreceptors;
   neuroprotection
ID INDUCED LIPID-PEROXIDATION; NITRIC-OXIDE SYNTHASE; MESSENGER-RNA LEVELS;
   GANGLION-CELL AXONS; MACULAR DEGENERATION; THERAPEUTIC STRATEGIES;
   ANTIGLAUCOMA DRUGS; OXIDATIVE STRESS; OPTIC-NERVE; VITAMIN-E
AB Flupirtine has been shown to function as a neuroprotectant and is presently used in man to treat a number of conditions. The aim of this study was to investigate the specific antioxidant properties of flupirtine in relation to oxidant-induced damage to retinal photoreceptors. Initial in vitro studies on brain membranes showed that flupirtine was approximately 20 times more potent than trolox (vitamin E analogue) and 8 times more potent than metipranolol at attenuating lipid peroxidation caused by the nitric oxide donor, sodium nitroprusside (SNP). Subsequent immunohistochemical studies revealed that following an intraocular injection of SNP, retinal photoreceptors are the only retinal cell types that appear to be clearly affected. This was supported by electroretinogram, (ERG) recordings which showed both the a- and b-wave amplitudes to be significantly reduced. Western blotting techniques showed that SNP caused a significant decrease in photoreceptor-specific markers (RET-P1, rhodopsin kinase), an increase in cleaved caspase-3, Bcl-2, and cleaved PARP proteins that are associated with apoptosis and no change in the ganglion cell specific marker, neurofilament (NF-L). This was supported by RT-PCR data where rhodopsin (photoreceptor specific) mRNA was reduced while Thy-1 and NF-L (ganglion cell specific) mRNAs were unaffected. In addition SNP caused an elevation of glial cell response mRNAs primarily associated with Muller cells (GFAP, CNTF, bFGF) as well as caspase-3 and Bcl-2. Importantly, when flupirtine was co-injected, the effects to the retina caused by SNP on retinal proteins and mRNAs were in most cases significantly blunted. The conclusion reached from this study is that flupirtine is a powerful antioxidant and when injected into the eye with SNP attenuates the detrimental influence of SNP to retinal photoreceptors. Since oxidative stress has been implicated in retinal diseases like age-related macular degeneration (AMD) this study provides "proof of principle" for the idea that flupirtine may help individuals suffering from such retinal diseases. (c) 2007 Elsevier Inc. All rights reserved.
C1 Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX2 6AW, England.
C3 University of Oxford
RP Osborne, NN (通讯作者)，Univ Oxford, Nuffield Lab Ophthalmol, Walton St, Oxford OX2 6AW, England.
EM neville.osborne@eye.ox.ac.uk
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NR 69
TC 13
Z9 13
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0361-9230
EI 1873-2747
J9 BRAIN RES BULL
JI Brain Res. Bull.
PD JUL 12
PY 2007
VL 73
IS 4-6
BP 278
EP 288
DI 10.1016/j.brainresbull.2007.04.002
PG 11
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 186JM
UT WOS:000247775000011
PM 17562394
DA 2022-11-30
ER

PT J
AU Klevering, BJ
   Deutman, AF
   Maugeri, A
   Cremers, FPM
   Hoyng, CB
AF Klevering, BJ
   Deutman, AF
   Maugeri, A
   Cremers, FPM
   Hoyng, CB
TI The spectrum of retinal phenotypes caused by mutations in the ABCA4 gene
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Review
ID CONE-ROD DYSTROPHY; STARGARDT-DISEASE GENE; RECESSIVE
   RETINITIS-PIGMENTOSA; MACULAR DEGENERATION; FUNDUS FLAVIMACULATUS;
   TRANSPORTER GENE; ALLELIC VARIATION; LIPOFUSCIN ACCUMULATION;
   BIOCHEMICAL DEFECTS; NONSENSE MUTATION
AB Background: The majority of studies on the retina-specific ATP-binding cassette transporter (ABCA4) gene have focussed on molecular genetic analysis; comparatively few studies have described the clinical aspects of ABCA4-associated retinal disorders. In this study, we demonstrate the spectrum of retinal dystrophies associated with ABCA4 gene mutations. Methods: Nine well-documented patients representing distinct phenotypes in the continuum of ABCA4-related disorders were selected. All patients received an extensive ophthalmologic evaluation, including kinetic perimetry, fluorescein angiography, and electroretinography (ERG). Mutation analysis had been performed previously with the genotyping microarray (ABCR400 chip) and/or single-strand conformation polymorphism analysis in combination with direct DNA sequencing. Results: In all patients, at least one pathologic ABCA4 mutation was identified. Patient 10034 represented the mild end of the phenotypic spectrum, demonstrating exudative age-related macular degeneration (AMD). Patient 24481 received the diagnosis of late-onset fundus flavimaculatus (FFM), patient 15168 demonstrated the typical FFM phenotype, and patient 19504 had autosomal recessive Stargardt disease (STGD1). Patients 11302 and 7608 exhibited progression from FFM/STGD1 to cone-rod dystrophy (CRD). A more typical CRD phenotype was found in patients 15680 and 12608. Finally, the most severe ABCA4-associated phenotype was retinitis pigmentosa (RP) in patient 11366. This phenotype was characterised by extensive atrophy with almost complete loss of peripheral and central retinal functions. Conclusion: We describe nine patients during different stages of disease progression; together, these patients form a continuum of ABCA4-associated phenotypes. Besides characteristic disorders such as FFM/STGD1, CRD and RP, intermediate phenotypes may be encountered. Moreover, as the disease progresses, marked differences may be observed between initially comparable phenotypes. In contrast, distinctly different phenotypes may converge to a similar final stage, characterised by extensive chorioretinal atrophy and very low visual functions. The identified ABCA4 mutations in most, but not all, patients were compatible with the resulting phenotypes, as predicted by the genotype-phenotype model for ABCA4-associated disorders. With the advent of therapeutic options, recognition by the general ophthalmologist of the various retinal phenotypes associated with ABCA4 mutations is becoming increasingly important.
C1 Univ Med Ctr Nijmegen, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands.
   Univ Med Ctr Nijmegen, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.
C3 Radboud University Nijmegen; Radboud University Nijmegen
RP Klevering, BJ (通讯作者)，Univ Med Ctr Nijmegen, Dept Ophthalmol, POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM b.klevering@ohk.umcn.nl
RI Cremers, Frans/A-5625-2014; Hoyng, C.B./H-8050-2014; Klevering,
   B.J./L-4434-2015
OI Cremers, Frans/0000-0002-4954-5592; 
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NR 63
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U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD FEB
PY 2005
VL 243
IS 2
BP 90
EP 100
DI 10.1007/s00417-004-1079-4
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 902PK
UT WOS:000227368800002
PM 15614537
DA 2022-11-30
ER

PT J
AU Hassan, SE
   Geruschat, DR
   Turano, KA
AF Hassan, SE
   Geruschat, DR
   Turano, KA
TI Head movements while crossing streets: Effect of vision impairment
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE head movements; street crossing; vision impairment; safety; pedestrian
ID CONTRAST SENSITIVITY; MACULAR SCOTOMAS; GAZE BEHAVIOR; MOTION; AGE;
   DIRECTION; GLAUCOMA; DESIGN; CHARTS; EYES
AB Background. Crossing the street is an activity that requires gathering information over a large area. The challenge in safely crossing a street is to acquire the necessary information for a decision of when to cross within a limited window of time. The purpose of this study was to compare the head movement behavior of visually impaired pedestrians with fully sighted pedestrians at two types of complex intersections: a plus intersection and a roundabout. Method. We measured the head movement behavior of 12 subjects with normal vision, I I subjects with age-related macular degeneration (AMD), and 10 subjects with glaucoma as they approached and crossed at the two intersections. The primary measures were the percentage of time the head was directed to the left, center, or right and the frequency of head turns. We compared measures across groups and relative to three criteria of head movement behavior for maximizing street-crossing safety. Results. Crossing the street can be divided into three phases: walking to the curb, standing at the curb, and crossing the street. We found that while moving, the majority of subjects directed their head to the center. This was true at the plus intersection and roundabout. Group differences were found in the frequency of head turns at the plus intersection, with the AMD pedestrians having a lower frequency of head turns compared with the fully sighted pedestrians. However, the frequency of head turns increased for all the groups during the last 4 seconds before crossing, with the frequency being the greatest during the last second. Numerous subjects had head movements consistent with pedestrian safety, although there were subjects in each group who failed to demonstrate maximum safety. More of the visually impaired pedestrians exhibited less safe head movement behavior than the fully sighted pedestrians. Conclusions. The effects of visual impairment on head movement behavior were associated with pedestrian safety at critical moments in the street-crossing process. Mobility training programs aimed at teaching safe head movement behavior for street crossing could help to increase the safety of visually impaired pedestrians.
C1 Maryland Sch Blind, Baltimore, MD USA.
   Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Hassan, SE (通讯作者)，Lions Vis Ctr, 550 N Broadway,6th Floor, Baltimore, MD 21205 USA.
EM shirin@lions.med.jhu.edu
FU NEI NIH HHS [R01 EY012894, EY12894] Funding Source: Medline; NATIONAL
   EYE INSTITUTE [R24EY012894, R01EY012894] Funding Source: NIH RePORTER
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NR 27
TC 14
Z9 15
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-5488
EI 1538-9235
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD JAN
PY 2005
VL 82
IS 1
BP 18
EP 26
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 889OH
UT WOS:000226451800005
PM 15630400
DA 2022-11-30
ER

PT J
AU Pitz, S
   Kramann, C
   Krummenauer, F
   Pitz, A
   Trabert, G
   Pfeiffer, N
AF Pitz, S
   Kramann, C
   Krummenauer, F
   Pitz, A
   Trabert, G
   Pfeiffer, N
TI Is homelessness a risk factor for eye disease? Results of a German
   screening study
SO OPHTHALMOLOGICA
LA English
DT Article
DE homelessness; poverty; blindness; optic nerve atrophy
ID OPEN-ANGLE GLAUCOMA; VISUAL IMPAIRMENT; BLINDNESS
AB Background: There is general agreement on the presence of a correlation between poverty and impaired health. However, only scarce data are available on whether this also applies to the incidence of eye disease. The present study was carried out to evaluate the prevalence of ocular disease in homeless people in Germany. Methods: 107 homeless people ( 97 male, 10 female; mean age 49 years, range 18 - 81 years) treated in specialised social service institutions were investigated prospectively according to a standardised ophthalmological screening protocol. This comprised visual acuity, assessment of pupillary light reaction, intra-ocular pressure, slit lamp examination as well as funduscopy. Results: The median best-corrected visual acuity of all 213 eyes examined was 0.8 ( range: no light perception to 1.25). 74 eyes of a subgroup of 50 patients showed one or more of the following disorders: 32% of the patients suffered from external eye disease, 8% exhibited a cataract associated with a visual acuity of 0.63 or below. 6% of the patients had optic nerve atrophy, and 4% suffered from amblyopia. Diabetic retinopathy as well as age-related macular degeneration were detected in 2%, while anophthalmos, lid malposition and traumatic choroidal rupture were noted in 1% of patients. The median visual acuity measured in these 74 eyes was 0.5 ( range: no light perception to 1.25), which differs significantly from the acuity of 0.8 in the entire study population ( p < 0.001). The prevalence of legal blindness according to WHO criteria was 2%. Conclusions: The present study revealed an unexpectedly high prevalence of optic nerve atrophy in homeless people. The prevalence for cataract and legal blindness was slightly higher than in representative epidemiological investigations. Thus, homelessness seems to be correlated with an increased ocular morbidity. As best-corrected visual acuity differed significantly between eyes with and those without eye disease, the assessment of this parameter may serve as a cost-effective first-stage screening method. Copyright (c) 2005 S. Karger AG, Basel.
C1 Univ Mainz, Dept Ophthalmol, D-6500 Mainz, Germany.
   Univ Mainz, Dept Med Biometry Epidemiol & Informat, D-6500 Mainz, Germany.
   Out Patient Clin Homeless People, Diakon Werk Hessen, Mainz, Germany.
   Georg Simon Ohm Fachhsch, Nurnberg, Germany.
C3 Johannes Gutenberg University of Mainz; Johannes Gutenberg University of
   Mainz
RP Pitz, S (通讯作者)，Univ Mainz, Dept Ophthalmol, D-6500 Mainz, Germany.
EM pitz@augen.klinik.uni-mainz.de
RI Pfeiffer, Norbert/AAO-7586-2020
CR BARBOSA R, 2002, 52 SESS REG WHO COMM
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NR 14
TC 19
Z9 19
U1 0
U2 2
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2005
VL 219
IS 6
BP 345
EP 349
DI 10.1159/000088376
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 985GK
UT WOS:000233364800005
PM 16286793
DA 2022-11-30
ER

PT J
AU Wang, F
   Hadzic, S
   Roxlau, ET
   Fuehler, B
   Janise-Libawski, A
   Wimmer, T
   Lei, B
   Li, SW
   Weissmann, N
   Stieger, K
AF Wang, Feng
   Hadzic, Stefan
   Roxlau, Elsa T.
   Fuehler, Baerbel
   Janise-Libawski, Annabella
   Wimmer, Tobias
   Lei, Bo
   Li, Shao-Wei
   Weissmann, Norbert
   Stieger, Knut
TI Retinal tissue develops an inflammatory reaction to tobacco smoke and
   electronic cigarette vapor in mice
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE AMD; C-cigarette smoke; E-cigarette vapor; Inflammatory reaction;
   Angiogenesis
ID MACULAR DEGENERATION; NICOTINE; RPE; INTERLEUKIN-1-BETA; GROWTH; PEDF;
   VEGF
AB Cigarette smoke has been identified as a major risk factor for the development of age-related macular degeneration (AMD). As an alternative to conventional cigarettes (C-cigarette), electronic cigarettes (E-cigarette) have been globally promoted and are currently widely used. The increasing usage of E-cigarettes raises concerns with regard to short- (2 weeks), medium- (3 months), and long- (8 months) term consequences related to retinal tissue. In this report, a controlled study in mouse models was conducted to probe the comprehensive effects of E-cigarette vapor on retina, retinal pigmented epithelium (RPE), and choroidal tissues by (1) comparing the effects of C-cigarette smoke and E-cigarette vapor on retina separately and (2) determining the effects of E-cigarette vapor on the RPE and analyzing the changes with regard to inflammatory (IL-1 beta, TNF alpha, iNOS) and angiogenic (VEGF, PEDF) mediators in retina/RPE/choroid by ELISA assays. The data showed that C-cigarette smoke exposure promoted an inflammatory reaction in the retina in vivo. Mice exposed to E-cigarette (nicotine-free) vapor developed inflammatory and angiogenic reactions more pronounced in RPE and choroid as compared to retinal tissue, while nicotine-containing E-cigarette vapor caused even a more serious reaction. Both inflammatory and pro-angiogenic reactions increased with the extension of exposure time. These results demonstrate that exposure to C-cigarette smoke is harmful to the retina. Likewise, the exposure to E-cigarette vapor (with or without nicotine) increases the occurrence and progression of inflammatory and angiogenic stimuli in the retina, which might also be related to the onset of wet AMD in humans. Key messages C-cigarette smoke exposure promotes an inflammatory reaction in the retina in vivo. Mice exposed to E-cigarette (nicotine-free) vapor develop inflammatory and angiogenic reactions more pronounced in RPE and choroid compared to retinal tissue, while nicotine-containing E-cigarette vapor causes even a more serious reaction. Both inflammatory and pro-angiogenic reactions increase with the extension of E-cigarette vapor exposure time.
C1 [Wang, Feng; Fuehler, Baerbel; Janise-Libawski, Annabella; Wimmer, Tobias; Stieger, Knut] Justus Liebig Univ Giessen, Dept Ophthalmol, Giessen, Germany.
   [Wang, Feng; Li, Shao-Wei] Cent South Univ, Aier Sch Ophthalmol, Dept Ophthalmol, Changsha, Peoples R China.
   [Hadzic, Stefan; Roxlau, Elsa T.; Weissmann, Norbert] Justus Liebig Univ, Univ Giessen & Marburg Lung Ctr UGMLC, German Ctr Lung Res DZL, Excellence Cluster Cardiopulm Inst CPI, Giessen, Germany.
   [Lei, Bo] Zhengzhou Univ, Peoples Hosp, Henan Prov People Hosp, Henan Eye Hosp,Henan Eye Inst, Zhengzhou, Peoples R China.
   [Li, Shao-Wei] Beijing Aier Intech Eye Hosp, Beijing, Peoples R China.
C3 Justus Liebig University Giessen; Central South University; Justus
   Liebig University Giessen; Zhengzhou University
RP Stieger, K (通讯作者)，Justus Liebig Univ Giessen, Dept Ophthalmol, Giessen, Germany.
EM Knut.stieger@uniklinikum-giessen.de
RI Hadzic, Stefan/GOJ-9706-2022
OI Hadzic, Stefan/0000-0001-8459-2776; Wang, Feng/0000-0002-0364-718X; Lei,
   Bo/0000-0002-5497-0905
FU German Research Foundation (DFG) [BE 4443/6-1, 268555672, SFB 1213];
   Excellence Cluster Cardio-Pulmonary Institute (CPI); Projekt DEAL
FX Open Access funding enabled and organized by Projekt DEAL. This research
   was supported by the German Research Foundation (DFG) (BE 4443/6-1 and
   Project-ID 268555672, SFB 1213: A06, A07) as well as the Excellence
   Cluster Cardio-Pulmonary Institute (CPI).
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TC 2
Z9 2
U1 1
U2 3
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0946-2716
EI 1432-1440
J9 J MOL MED
JI J. Mol. Med.
PD OCT
PY 2021
VL 99
IS 10
BP 1459
EP 1469
DI 10.1007/s00109-021-02108-9
EA JUL 2021
PG 11
WC Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Research & Experimental Medicine
GA US8JN
UT WOS:000673860800001
PM 34264377
OA hybrid, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Bonadiman, BDR
   Chaves, C
   Assmann, CE
   Weis, GCC
   Alves, AD
   Gindri, AL
   Chaves, C
   da Cruz, IBM
   Zamoner, A
   Bagatini, MD
AF Bonadiman, Beatriz da Silva Rosa
   Chaves, Claudia
   Assmann, Charles Elias
   Weis, Grazielle Castagna Cezimbra
   Alves, Audrei de Oliveira
   Gindri, Amanda Leitao
   Chaves, Claudio
   da Cruz, Ivana Beatrice Manica
   Zamoner, Ariane
   Bagatini, Margarete Dulce
TI Tucuma (Astrocaryum aculeatum) Prevents Oxidative and DNA Damage to
   Retinal Pigment Epithelium Cells
SO JOURNAL OF MEDICINAL FOOD
LA English
DT Article
DE Amazon fruit; antioxidant; DNA damage; eye; elderly
AB Eye diseases have a negative impact on the eyesight quality of the world population. The age-related macular degeneration (AMD) draws special attention since it is a chronic disorder characterized by oxidative and inflammatory damage to the retinal epithelial pigment, which triggers progressive vision loss. In the Brazilian Amazon, Astrocaryum aculeatum is an Amazonian fruit (Tucuma) used by riverside communities in traditional medicine to treat a number of ailments. These communities have recently shown to have increased longevity and reduced prevalence of age-related morbidity. Thus, the aim of this research was to chemically characterize and analyze the in vitro antioxidant effect and molecular damage prevention of the Tucuma ethanolic extract in retinal pigment epithelium (RPE) cells in a model for AMD. The extract was chemically characterized by ultra-high-performance liquid chromatography (HPLC) coupled with diode-array detection and mass spectrophotometry (HPLC-DAD-MS). In vitro protocols were performed, and the cytopreventive effect of Tucuma on RPE cells exposed to high concentrations of superoxide anion, an oxidant and genotoxic molecule, as well as the effect of Tucuma extract on oxidative and molecular makers were assessed. Biochemical and flow cytometry analyses were conducted in these protocols. The extract presents high concentrations of caffeic acid, gallic acid, catechin, luteolin, quercetin, and rutin. Treatment did not show cytotoxic effects in cells treated only with extract at 50 mu g/mL. In fact, it improved cell viability and was able to prevent necrosis and apoptosis, and oxidative and molecular damage was significantly reduced. In summary, Tucuma is an important Amazon fruit, which seems to contribute significantly to improve human health conditions, as our findings suggest that its extract has a relevant chemical matrix rich in antioxidant molecules, and its consumption could improve eye health and contribute to prevention against oxidative stress through cytoprevention, reactive oxygen species reduction, and maintenance of DNA integrity in retinal pigment epithelium (RPE) cells.
C1 [Bonadiman, Beatriz da Silva Rosa; Zamoner, Ariane] Univ Fed Santa Catarina, Biol Sci Ctr, Dept Biochem, Florianopolis, SC, Brazil.
   [Chaves, Claudia] Nilton Lins Univ, Dept Ophthalmol, Hlth Sci Ctr, Manaus, Amazonas, Brazil.
   [Assmann, Charles Elias] Univ Fed Santa Maria, Dept Biochem & Mol Biol, Santa Maria, RS, Brazil.
   [Weis, Grazielle Castagna Cezimbra] Univ Fed Santa Maria, Dept Food Sci & Technol, Santa Maria, RS, Brazil.
   [Alves, Audrei de Oliveira] Univ Fed Santa Maria, Dept Physiol & Pharmacol, Santa Maria, RS, Brazil.
   [da Cruz, Ivana Beatrice Manica] Univ Fed Santa Maria, Dept Morphol, Santa Maria, RS, Brazil.
   [Gindri, Amanda Leitao] Integrated Reg Univ Upper Uruguay & Miss URI, Dept Biol Sci Ctr, Santiago, Brazil.
   [Chaves, Claudio] Ophthalmol Inst Manaus, Dept Ophthalmol, Manaus, Amazonas, Brazil.
   [Bagatini, Margarete Dulce] Fed Univ Fronteira Sul, Grad Program Biomed Sci, Campus Chapeco, BR-89815899 Chapeco, SC, Brazil.
C3 Universidade Federal de Santa Catarina (UFSC); Centro Universitario
   Nilton Lins; Universidade Federal de Santa Maria (UFSM); Universidade
   Federal de Santa Maria (UFSM); Universidade Federal de Santa Maria
   (UFSM); Universidade Federal de Santa Maria (UFSM); Universidade Federal
   da Fronteira Sul
RP Bagatini, MD (通讯作者)，Fed Univ Fronteira Sul, Grad Program Biomed Sci, Campus Chapeco, BR-89815899 Chapeco, SC, Brazil.
EM margaretebagatini@yahoo.com.br
RI da Cruz, Ivana BM/G-4329-2012; Assmann, Charles/AAM-8039-2021; Bagatini,
   Margarete/K-3756-2016; Zamoner, A./D-9525-2012
OI da Cruz, Ivana BM/0000-0003-3008-6899; Bagatini,
   Margarete/0000-0001-9263-4980; Zamoner, A./0000-0003-2844-8563
FU "Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior'' (CAPES)
   [402325/2013-3, 490760/2013-9, 311446/2012-4]
FX This work was supported with grants (Grant Nos. 402325/2013-3,
   490760/2013-9 and 311446/2012-4) from the "Coordenacao de
   Aperfeicoamento de Pessoal de Nivel Superior'' (CAPES).
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NR 29
TC 1
Z9 1
U1 3
U2 5
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-620X
EI 1557-7600
J9 J MED FOOD
JI J. Med. Food
PD OCT 1
PY 2021
VL 24
IS 10
BP 1050
EP 1057
DI 10.1089/jmf.2020.0171
EA MAR 2021
PG 8
WC Chemistry, Medicinal; Food Science & Technology; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Food Science & Technology; Nutrition &
   Dietetics
GA XB8RZ
UT WOS:000635567300001
PM 33769097
DA 2022-11-30
ER

PT J
AU Tien, PT
   Lin, HJ
   Tsai, YY
   Lim, YP
   Chen, CS
   Chang, CY
   Lin, CJ
   Chen, JJY
   Wu, SM
   Huang, YJ
   Wan, L
AF Tien, Peng-Tai
   Lin, Hui-Ju
   Tsai, Yi-Yu
   Lim, Yun-Ping
   Chen, Chih Sheng
   Chang, Ching-Yao
   Lin, Chao-Jen
   Chen, Jamie Jiin-Yi
   Wu, Shan-Mei
   Huang, Yuh-Jeen
   Wan, Lei
TI Perfluorooctanoic acid in indoor particulate matter triggers oxidative
   stress and inflammation in corneal and retinal cells
SO SCIENTIFIC REPORTS
LA English
DT Article
AB To investigate the particle size distribution of particulate matter and the concentration of specific perfluorinated compounds in indoor dust samples from several locations. Then, we used cell-based assays to investigate the effect of perfluorinated compounds on human corneal epithelial (HCEpiC), endothelial cells (HCEC) and retinal pigment epithelial cells (RPE). Indoor dust samples were collected at five different locations and PM50-10, PM10-2.5, and PM2.5-1 were fractionized. The presence and levels of 8:2 fluorotelomer alcohol, 10:2 fluorotelomer alcohol, and perfluorooctanoic acid were detected by gas chromatography-mass spectrometry. The effect of perfluorooctanoic acid on the activation of reactive oxygen species, transepithelial resistance as well as the expression of interleukin (IL)-6 and IL-8 were determined. The basolateral media of human corneal epithelial or human corneal endothelial cells were used to treat human corneal endothelial or retinal pigment epithelial cells, respectively to indicate the potential of ocular surface inflammation may result in retinal inflammation. Among perfluorinated compounds, only perfluorooctanoic acid was detected in all indoor dust samples. Perfluorooctanoic acid had the highest concentration among all perfluorinated compounds in the samples. Exposure to perfluorooctanoic acid impaired tight junction sealing and increased the levels of reactive oxygen species in human corneal epithelial cells. In human corneal epithelial cells, secretion of IL-6 and IL-8 in both apical and basolateral media was promoted significantly by perfluorooctanoic acid treatment. Stimulation with the basolateral media from perfluorooctanoic acid-treated human corneal epithelial cells induced inflammation in human corneal endothelial cells. The treatment of retinal pigment epithelial cells with the basolateral media from stimulated human corneal endothelial cells also elicited the secretion of proinflammatory cytokines. The results indicate that perfluorooctanoic acid exposure impaired the tight junction of corneal cells and caused inflammatory reactions in the retina. Exposure of the cornea to perfluorooctanoic acid contained in particulate matter might induce oxidative stress and inflammation in the retina and represent a risk factor for age-related macular degeneration.
C1 [Tien, Peng-Tai; Tsai, Yi-Yu] China Med Univ, Coll Med, Grad Inst Clin Med Sci, Taichung, Taiwan.
   [Tien, Peng-Tai; Lin, Hui-Ju; Tsai, Yi-Yu; Chen, Jamie Jiin-Yi] China Med Univ Hosp, Dept Ophthalmol, Taichung, Taiwan.
   [Lin, Hui-Ju; Chen, Chih Sheng; Wan, Lei] China Med Univ, Sch Chinese Med, 91 Hsueh Shih Rd, Taichung 40402, Taiwan.
   [Lim, Yun-Ping] China Med Univ, Coll Pharm, Dept Pharm, Taichung, Taiwan.
   [Chen, Chih Sheng] Asia Univ Hosp, Div Chinese Med, Taichung, Taiwan.
   [Chang, Ching-Yao; Wan, Lei] Asia Univ, Dept Biotechnol, Taichung, Taiwan.
   [Lin, Chao-Jen] Changhua Christian Childrens Hosp, Dept Pediat, Changhua, Taiwan.
   [Lin, Chao-Jen] Chung Shan Med Univ, Sch Med, Taichung, Taiwan.
   [Wu, Shan-Mei; Huang, Yuh-Jeen] Natl Tsing Hua Univ, Dept Biomed Engn & Environm Sci, 101 Sect 2,Kuang Fu Rd, Hsinchu, Taiwan.
   [Huang, Yuh-Jeen] Natl Tsing Hua Univ, Inst Analyt & Environm Sci, Hsinchu, Taiwan.
   [Wan, Lei] China Med Univ Hosp, Dept Obstet & Gynecol, Taichung, Taiwan.
C3 China Medical University Taiwan; China Medical University Taiwan; China
   Medical University Hospital - Taiwan; China Medical University Taiwan;
   China Medical University Taiwan; Asia University Taiwan; Chung Shan
   Medical University; National Tsing Hua University; National Tsing Hua
   University; China Medical University Taiwan; China Medical University
   Hospital - Taiwan
RP Wan, L (通讯作者)，China Med Univ, Sch Chinese Med, 91 Hsueh Shih Rd, Taichung 40402, Taiwan.; Wan, L (通讯作者)，Asia Univ, Dept Biotechnol, Taichung, Taiwan.; Huang, YJ (通讯作者)，Natl Tsing Hua Univ, Dept Biomed Engn & Environm Sci, 101 Sect 2,Kuang Fu Rd, Hsinchu, Taiwan.; Huang, YJ (通讯作者)，Natl Tsing Hua Univ, Inst Analyt & Environm Sci, Hsinchu, Taiwan.; Wan, L (通讯作者)，China Med Univ Hosp, Dept Obstet & Gynecol, Taichung, Taiwan.
EM yjhuang@mx.nthu.edu.tw; leiwan@cmu.edu.tw
FU Ministry of Science and Technology, Taiwan, R.O.C.
   [MOST103-2221-E-007-006-MY3, MOST103-2314-B-039-035-MY3,
   MOST105-2628-B-039-008-MY3]; China Medical University Hospital,
   Taichung, Taiwan [DMR-106-149]; China Medical University, Taichung,
   Taiwan [CMU103-BC-3-2, CMU108-MF-40]
FX This study was supported in part by the Ministry of Science and
   Technology, Taiwan, R.O.C. (MOST103-2221-E-007-006-MY3,
   MOST103-2314-B-039-035-MY3 and MOST105-2628-B-039-008-MY3), China
   Medical University Hospital, Taichung, Taiwan (DMR-106-149), and China
   Medical University, Taichung, Taiwan (CMU103-BC-3-2; CMU108-MF-40). The
   sponsor or funding organization had no role in the design or conduct of
   this research.
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NR 47
TC 4
Z9 3
U1 8
U2 17
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD SEP 24
PY 2020
VL 10
IS 1
AR 15702
DI 10.1038/s41598-020-72600-8
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA QD2RG
UT WOS:000615371600019
PM 32973190
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Perdomo, O
   Rios, H
   Rodriguez, FJ
   Otalora, S
   Meriaudeaue, F
   Muller, H
   Gonzalez, FA
AF Perdomo, Oscar
   Rios, Hernan
   Rodriguez, Francisco J.
   Otalora, Sebastian
   Meriaudeaue, Fabrice
   Mueller, Henning
   Gonzalez, Fabio A.
TI Classification of diabetes-related retinal diseases using a deep
   learning approach in optical coherence tomography
SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
LA English
DT Article
DE Optical coherence tomography; Deep learning models; Interpretability;
   Retinal diseases; Medical findings
ID MACULAR DEGENERATION; RETINOPATHY; ANGIOGRAPHY
AB Background and objectives: Spectral Domain Optical Coherence Tomography (SD-OCT) is a volumetric imaging technique that allows measuring patterns between layers such as small amounts of fluid. Since 2012, automatic medical image analysis performance has steadily increased through the use of deep learning models that automatically learn relevant features for specific tasks, instead of designing visual features manually. Nevertheless, providing insights and interpretation of the predictions made by the model is still a challenge. This paper describes a deep learning model able to detect medically interpretable information in relevant images from a volume to classify diabetes-related retinal diseases.
   Methods: This article presents a new deep learning model, OCT-NET, which is a customized convolutional neural network for processing scans extracted from optical coherence tomography volumes. OCT-NET is applied to the classification of three conditions seen in SD-OCT volumes. Additionally, the proposed model includes a feedback stage that highlights the areas of the scans to support the interpretation of the results. This information is potentially useful for a medical specialist while assessing the prediction produced by the model.
   Results: The proposed model was tested on the public SERI-CUM< and A2A SD-OCT data sets containing healthy, diabetic retinopathy, diabetic macular edema and age-related macular degeneration. The experimental evaluation shows that the proposed method outperforms conventional convolutional deep learning models from the state of the art reported on the SERI+CUI-IK and A2A SD-OCT data sets with a precision of 93% and an area under the ROC curve (AUC) of 0.99 respectively.
   Conclusions: The proposed method is able to classify the three studied retinal diseases with high accuracy. One advantage of the method is its ability to produce interpretable clinical information in the form of highlighting the regions of the image that most contribute to the classifier decision. (C) 2019 Elsevier B.V. All rights reserved.
C1 [Perdomo, Oscar; Gonzalez, Fabio A.] Univ Nacl Colombia, MindLab Res Grp, Edificio 453,Lab 207, Bogota, Colombia.
   [Rios, Hernan; Rodriguez, Francisco J.] Fdn Oftalmol Nacl, Bogota, Colombia.
   [Otalora, Sebastian; Mueller, Henning] Univ Appl Sci Western Switzerland, HES SO, Sierre, Switzerland.
   [Otalora, Sebastian; Mueller, Henning] Univ Geneva, Geneva, Switzerland.
   [Meriaudeaue, Fabrice] Univ Bourgogne Franche Comte, ImvIA EA7535 IFTIM, Besancon, France.
C3 Universidad Nacional de Colombia; University of Applied Sciences & Arts
   Western Switzerland; University of Geneva; Universite de Bourgogne
RP Perdomo, O; Gonzalez, FA (通讯作者)，Univ Nacl Colombia, MindLab Res Grp, Edificio 453,Lab 207, Bogota, Colombia.
EM fagonzalezo@unal.edu.co
RI Otálora, Sebastian/AAD-8200-2019; Perdomo Charry, Oscar
   Julian/G-4454-2011; Gonzalez, Fabio/B-9502-2008
OI Otálora, Sebastian/0000-0003-2125-8476; Perdomo Charry, Oscar
   Julian/0000-0001-9493-2324; Gonzalez, Fabio/0000-0001-9009-7288;
   Rodriguez, Francisco J/0000-0002-1728-3444; MERIAUDEAU,
   Fabrice/0000-0002-8656-9913; Muller, Henning/0000-0001-6800-9878; Rios,
   Hernan/0000-0002-9422-7112
FU project Deteccion temprana de dano ocular en diabeticos usando un
   sistema de inteligencia artificial en imagenes de fondo de ojo of
   Colciencias by Convocatoria Colciencias [1101-807-63563 CT];
   COLCIENCIAS; Colciencias [756]; Nvidia; TitanX GPU
FX This work was funded by the project Deteccion temprana de dano ocular en
   diabeticos usando un sistema de inteligencia artificial en imagenes de
   fondo de ojo number 1101-807-63563 CT of Colciencias by Convocatoria
   Colciencias 837 de 2018. Oscar Perdomo thanks COLCIENCIAS for funding
   this research with a doctoral grant. Sebastian Otalora thanks
   Colciencias for funding partially this research with a doctoral grant
   through the call 756 for PhD. programs. We appreciate the efforts
   devoted by: Prof. Sina Farsiu and Prof. Cynthia A. Toth from Duke
   University; Carol Cheung and Tien Y Wong from the Chinese University of
   Hong Kong (CUHK) and Singapore Eye Research Institute (SERI) to collect
   SDOCT volumes. This work was partially supported by Nvidia with a TitanX
   GPU.
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NR 38
TC 27
Z9 28
U1 4
U2 29
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0169-2607
EI 1872-7565
J9 COMPUT METH PROG BIO
JI Comput. Meth. Programs Biomed.
PD SEP
PY 2019
VL 178
BP 181
EP 189
DI 10.1016/j.cmpb.2019.06.016
PG 9
WC Computer Science, Interdisciplinary Applications; Computer Science,
   Theory & Methods; Engineering, Biomedical; Medical Informatics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Medical Informatics
GA IQ0HP
UT WOS:000480432000019
PM 31416547
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Nag, TC
   Wadhwa, S
AF Nag, Tapas Chandra
   Wadhwa, Shashi
TI Immunolocalisation pattern of complex I-V in ageing human retina:
   Correlation with mitochondrial ultrastructure
SO MITOCHONDRION
LA English
DT Article
DE Retina; Ageing; Oxidative phosphorylation; Photoreceptors; Complex I;
   Mitochondria
ID CYTOCHROME-C-OXIDASE; MACULAR DEGENERATION; OXIDATIVE DAMAGE;
   HISTOCHEMICAL-LOCALIZATION; DNA DAMAGE; RAT RETINA; PHOTORECEPTORS;
   STRESS; MONKEY; ABNORMALITIES
AB Earlier studies reported accumulation of mitochondrial DNA mutations in ageing and age-related macular degeneration. To know about the mitochondrial status with age, we examined immunoreactivity (IR) to markers of mitochondria (anti-mitochondrial antibody and voltage-dependent anion channel-1) and complex I-V (that mediate oxidative phosphorylation, OXPHOS) in donor human retinas (age: 19-94 years; N = 26; right eyes). In all samples, at all ages, IR to anti-mitochondrial antibody and voltage-dependent anion channel-1 was prominent in photoreceptor cells. Between second and seventh decade of life, strong IR to complex I-V was present in photoreceptors over macular to peripheral retina. With progressive ageing, the photoreceptors showed a decrease in complex I-IR (subunit NDUFB4) at eighth decade, and a weak or absence of IR in 10 retinas between ninth and tenth decade. Patchy IR to complex III and complex IV was detected at different ages. IR to ND1 (complex I) and complex II and V remained unaltered with ageing. Nitrosative stress (evaluated by IR to a nitro-tyrosine antibody) was found in photoreceptors. Superoxide dismutase-2 was found upregulated in photoreceptors with ageing. Mitochondrial ultra structure was examined in two young retinas with intact complex IR and six aged retinas whose counterparts showed weak to absence of IR. Observations revealed irregular, photoreceptor inner segment mitochondria in aged maculae and mid-peripheral retina between eighth and ninth decade; many cones possessed autophagosomes with damaged mitochondria, indicating age-related alterations. A trend in age-dependent reduction of complexI-IR was evident in aged photoreceptors, whereas patchy complex IV-IR (subunits I and II) was age independent, suggesting that the former is prone to damage with ageing perhaps due to oxidative stress. These changes in OXPHOS system may influence the energy budget of human photoreceptors, affecting their viability. (C) 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
C1 [Nag, Tapas Chandra; Wadhwa, Shashi] All India Inst Med Sci, Neurobiol Lab, Dept Anat, New Delhi 110029, India.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi
RP Nag, TC (通讯作者)，All India Inst Med Sci, Neurobiol Lab, Dept Anat, New Delhi 110029, India.
EM tapas_nag@yahoo.com
RI NAG, TAPAS CHANDRA/R-6285-2019
OI NAG, TAPAS CHANDRA/0000-0002-6962-0844
FU DBT, Government of India [BT/PR10195/BRB/10/589/2007]; Institute
   research grant, AIIMS, New Delhi [F.1-6-Para-Med/Acad]
FX We thank The Officer-In-Charge, National Eye Bank, AIIMS, New Delhi for
   providing us with the donor human eyes. The TEM was done at SAIF-AIIMS
   (New Delhi). The work was financially supported from DBT, Government of
   India (BT/PR10195/BRB/10/589/2007) and Institute research grant, AIIMS,
   New Delhi (F.1-6-Para-Med/Acad,2008).
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NR 58
TC 13
Z9 13
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1567-7249
EI 1872-8278
J9 MITOCHONDRION
JI Mitochondrion
PD NOV
PY 2016
VL 31
BP 20
EP 32
DI 10.1016/j.mito.2016.08.016
PG 13
WC Cell Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Genetics & Heredity
GA EC8ZL
UT WOS:000388431500003
PM 27581213
DA 2022-11-30
ER

PT J
AU Wong, CW
   Lamoureux, EL
   Cheng, CY
   Cheung, GCM
   Tai, ES
   Wong, TY
   Sabanayagam, C
AF Wong, Chee Wai
   Lamoureux, Ecosse L.
   Cheng, Ching-Yu
   Cheung, Gemmy Chui Ming
   Tai, E. Shyong
   Wong, Tien Y.
   Sabanayagam, Charumathi
TI Increased Burden of Vision Impairment and Eye Diseases in Persons with
   Chronic Kidney Disease - A Population-Based Study
SO EBIOMEDICINE
LA English
DT Article
DE Chronic kidney disease; Visual impairment; Ocular disease; Cataract;
   Retinopathy
ID VISUAL IMPAIRMENT; MACULAR DEGENERATION; RISK-FACTORS; PREVALENCE;
   MORTALITY; ABNORMALITIES; ALBUMINURIA; GLYCATION; CATARACT; IMPACT
AB Background: Chronic kidney disease (CKD) has been shown to be associated with diabetic retinopathy (DR) and age-related macular degeneration (AMD), leading causes of blindness in elderly adults in previous studies. However, the association of CKD with visual impairment (VI) is not clear. We aimed to examine the association of CKD with VI and other age-related ocular diseases in a population-based sample of Asian adults.
   Methods: We analyzed data from 10,033 adults aged 40-80 years who participated in the Singapore Epidemiology of Eye Diseases (SEED, 2004-11) Study. CKD was defined as an estimated glomerular filtration rate (eGFR) b60 ml/min/1.73 m(2) from serum creatinine. VI was defined as best-corrected visual acuity <20/40 in the better eye. Cataract, retinopathy, DR, glaucoma and AMD were assessed using standardized ocular examination, retinal photography and visual field assessments. The associations of CKD with VI and ocular conditions were examined using logistic regression models adjusted for age, sex, race, smoking, alcohol intake, education status, body mass index, systolic blood pressure, diabetes mellitus, cholesterol levels and cardiovascular disease.
   Findings: The prevalence of VI and ocular disease were significantly higher in participants with CKD (36.1% and 84.7%) than in those without (12.9% and 54.3%, both p < 0.001). In multivariable models, CKD was significantly associated with VI (odds ratio [95% confidence interval] = 1.34 [1.14-1.58]), any ocular disease (1.28 [1.03-1.61]), cataract (1.24 [1.01-1.52]), any retinopathy (1.77 [1.45-2.15]), and DR (1.94 [1.47-2.54]).
   Interpretation: The burden of VI and eye diseases is high among persons with CKD. Our findings suggest that it may be useful to screen for ocular disease and VI in persons with CKD. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Wong, Chee Wai; Lamoureux, Ecosse L.; Cheng, Ching-Yu; Cheung, Gemmy Chui Ming; Wong, Tien Y.; Sabanayagam, Charumathi] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Lamoureux, Ecosse L.; Cheng, Ching-Yu; Wong, Tien Y.; Sabanayagam, Charumathi] Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
   [Lamoureux, Ecosse L.; Cheng, Ching-Yu; Cheung, Gemmy Chui Ming; Wong, Tien Y.; Sabanayagam, Charumathi] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore.
   [Tai, E. Shyong] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; National University of Singapore;
   National University of Singapore
RP Sabanayagam, C (通讯作者)，Singapore Eye Res Inst, 20 Coll Rd,Discovery Tower Level 6, Singapore 169856, Singapore.
EM charumathi.sabanayagam@seri.com.sg
RI Lamoureux, Ecosse/Z-5482-2019; Cheng, Ching-Yu/Y-2229-2019; Wong, Tien
   Yin/AAC-9724-2020; Sabanayagam, Charumathi/C-1294-2011
OI Cheng, Ching-Yu/0000-0003-0655-885X; Wong, Tien Yin/0000-0002-8448-1264;
   Sabanayagam, Charumathi/0000-0002-4042-4719; Tai, E
   Shyong/0000-0003-2929-8966; Cheung, Chui Ming Gemmy/0000-0003-3358-3516;
   Wong, Chee Wai/0000-0002-0935-2016
FU Biomedical Research Council (BMRC) [08/1/35/19/550]; National Medical
   Research Council (NMRC), Singapore [STaR/0003/2008]; Ministry of Health
   - Singapore's National Medical Research Council under its Talent
   Development Scheme [R927/36/2012]
FX This study was funded by Biomedical Research Council (BMRC),
   08/1/35/19/550 and National Medical Research Council (NMRC),
   STaR/0003/2008, Singapore and Ministry of Health - Singapore's National
   Medical Research Council under its Talent Development Scheme
   R927/36/2012 (CS). The funding agencies had no role in the conduct or
   interpretation of the study.
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NR 30
TC 37
Z9 40
U1 0
U2 4
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD MAR
PY 2016
VL 5
BP 193
EP 197
DI 10.1016/j.ebiom.2016.01.023
PG 5
WC Medicine, General & Internal; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Research & Experimental Medicine
GA DK7AW
UT WOS:000375078200034
PM 27077127
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Stark, K
   Olden, M
   Brandl, C
   Dietl, A
   Zimmermann, ME
   Schelter, SC
   Loss, J
   Leitzmann, MF
   Boger, CA
   Luchner, A
   Kronenberg, F
   Helbig, H
   Weber, BHF
   Heid, IM
AF Stark, Klaus
   Olden, Matthias
   Brandl, Caroline
   Dietl, Alexander
   Zimmermann, Martina E.
   Schelter, Sabine C.
   Loss, Julika
   Leitzmann, Michael F.
   Boeger, Carsten A.
   Luchner, Andreas
   Kronenberg, Florian
   Helbig, Horst
   Weber, Bernhard H. F.
   Heid, Iris M.
TI The German AugUR study: study protocol of a prospective study to
   investigate chronic diseases in the elderly
SO BMC GERIATRICS
LA English
DT Article
DE Mobile elderly population; Cross-sectional study; Cohort study; Etiology
   of chronic diseases; Diseases of late onset; Study platform; Genetic and
   non-genetic risk factors
ID EUROPEAN-ASSOCIATION; NATIONAL COHORT; ECHOCARDIOGRAPHIC-ASSESSMENT;
   MACULAR DEGENERATION; AMERICAN-SOCIETY; PHOTOSTRESS TEST;
   RECOMMENDATIONS; HEART; HERITABILITY; GUIDELINES
AB Background: The majority of patients suffering from chronic health disabilities is beyond 70 years of age. Typical late-onset chronic diseases include those affecting the heart, the kidney, cancer, and conditions of the eye such as age-related macular degeneration. These diseases disable patients for many years and largely compromise autonomy in daily life. Due to challenges in recruiting the elderly, the collection of population-based epidemiological data as a prerequisite to understand associated risk factors and mechanisms is commonly done in the general population within an age-range of 20 to 70 years.
   Methods/Design: We establish the German AugUR study (Age-related diseases: understanding genetic and non-genetic influences - a study at the University of Regensburg), a prospective study in the mobile elderly general population in and around Regensburg in eastern Bavaria. In the long term, we aim to recruit 3,000 persons of Caucasian ethnicity with at least 70 years of age via residents' registration offices and conduct 3-year follow-ups. The study protocol includes a standardized interview regarding social and life-style factors, medication history, quality-of-life, and existing diagnoses of common diseases. The participants undergo medical examinations for ophthalmological, cardiovascular or diabetes-related conditions, and general measurements of body shape and fitness. The program is particularly tailored for the elderly. Biobanking of whole blood, serum, plasma, and urine is conducted and standard laboratory measurements are performed in fresh samples.
   Discussion: AugUR is specifically designed as a research platform to host studies of late onset diseases. Consequently, this platform will help (1) to unravel the genetic and non-genetic etiology of disease development and progression, (2) to serve as control group of elderly individuals for comparisons with various patient groups, (3) to derive prevalence and incidence data on chronic diseases, and (4) to provide clinical reference parameters for the elderly mobile general population. This data will foster our understanding of disease mechanisms, which may ultimately help to improve prevention, diagnosis, and therapy for frequent chronic diseases. Here we present the baseline study protocol of AugUR.
C1 [Stark, Klaus; Olden, Matthias; Brandl, Caroline; Dietl, Alexander; Zimmermann, Martina E.; Schelter, Sabine C.; Heid, Iris M.] Univ Regensburg, Dept Genet Epidemiol, D-93053 Regensburg, Germany.
   [Brandl, Caroline; Helbig, Horst] Univ Hosp Regensburg, Dept Ophthalmol, Regensburg, Germany.
   [Brandl, Caroline; Weber, Bernhard H. F.] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
   [Dietl, Alexander; Luchner, Andreas] Univ Hosp Regensburg, Dept Internal Med 2, Regensburg, Germany.
   [Schelter, Sabine C.] Univ Hosp Regensburg, Ctr Clin Studies, Regensburg, Germany.
   [Loss, Julika; Leitzmann, Michael F.] Univ Regensburg, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany.
   [Boeger, Carsten A.] Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany.
   [Kronenberg, Florian] Med Univ Innsbruck, Div Genet Epidemiol, A-6020 Innsbruck, Austria.
C3 University of Regensburg; University of Regensburg; University of
   Regensburg; University of Regensburg; University of Regensburg;
   University of Regensburg; University of Regensburg; Medical University
   of Innsbruck
RP Heid, IM (通讯作者)，Univ Regensburg, Dept Genet Epidemiol, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany.
EM Iris.Heid@klinik.uni-regensburg.de
RI Kronenberg, Florian/B-1736-2008; Stark, Klaus/L-7367-2013; Zimmermann,
   Martina/AAL-2990-2021
OI Kronenberg, Florian/0000-0003-2229-1120; Stark,
   Klaus/0000-0002-7832-1942; Zimmermann, Martina/0000-0002-6916-4404;
   Weber, Bernhard H.F./0000-0002-8808-7723; Brandl,
   Caroline/0000-0001-8223-6137
FU German Federal Ministry of Education and Research [BMBF 01ER1206]
FX This study is supported by a grant from the German Federal Ministry of
   Education and Research (BMBF 01ER1206).
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NR 31
TC 19
Z9 19
U1 0
U2 7
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2318
J9 BMC GERIATR
JI BMC Geriatr.
PD OCT 21
PY 2015
VL 15
AR 130
DI 10.1186/s12877-015-0122-0
PG 8
WC Geriatrics & Gerontology; Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Geriatrics & Gerontology
GA CX2YF
UT WOS:000365562000001
PM 26489512
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Tan, X
   Takahashi, H
   Nishida, J
   Aoki, A
   Inoue, T
   Yanagi, Y
AF Tan, Xue
   Takahashi, Hidenori
   Nishida, Junko
   Aoki, Aya
   Inoue, Tatsuya
   Yanagi, Yasuo
TI Excessive retinol intake exacerbates choroidal neovascularization
   through upregulated vascular endothelial growth factor in retinal
   pigment epithelium in mice
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Visual cycle; VEGF; Angiogenesis; Moderator
ID AGE-RELATED MACULOPATHY; RETINOBLASTOMA Y79 CELLS; VEGF GENE-EXPRESSION;
   VITAMIN-A; BINDING-PROTEIN; MACULAR DEGENERATION; ACID RECEPTOR; VISUAL
   CYCLE; ALPHA-TOCOPHEROL; BETA-CAROTENE
AB As a part of the visual cycle, all-trans-retinol (all-trans-ROL), the major form of vitamin A in circulating blood, is transported to the retinal pigment epithelium (RPE). All-trans-ROL is essential for normal retina function. However, recent researches have shown that excessive retinol intake can cause increase of all-trans-retinal. This can lead to the accumulation of lipofuscin, which is important in the pathogenesis of retina degeneration disease, such as dry type age-related macular degeneration (AMD). Since there are few reports regarding the involvement of all-trans-ROL in exudative AMD, we investigated the effects of all-trans-ROL in vitro and in vivo. We evaluated vascular endothelial growth factor (VEGF) expression in ARPE-19 cells and THP-1 cells after all-trans-ROL treatment using ELISA and real-time RT-PCR. In-vitro tube formation assay was performed with HUVEC cells using the conditioned medium (CM) obtained from ARPE-19 cells treated with all-trans-ROL. Transcriptional activity of retinoic acid receptor (RAR) was evaluated using luciferase assay. In mice, VEGF expressions were investigated in the retina and RPE/choroid after three weeks of excessive oral retinol intake. Laser-induced choroidal neovascularization (CNV) models were evaluated after they were fed with various doses of retinol. VEGF mRNA expression and VEGF production were significantly increased in all-trans-ROL treated ARPE-19 cells, which were inhibited by an RAR antagonist LE540. In contrast, there were no significant changes in VEGF production in THP-1 cells. Transcriptional activity of RAR was upregulated by all-trans-ROL treatment in ARPE-19 cells. The CM, obtained from ARPE-19 cells treated with all-trans-ROL, induced more capillary-like tube formation than cells treated with control vehicles. In vivo, the high retinal diet group has increased VEGF expression in the RPE/choroid and larger lesion size was induced. Our results suggest that all-trans-ROL is a pro-angiogenic factor. Excessive retinoid intake may be a potential risk factor for exudative AMD. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Tan, Xue; Takahashi, Hidenori; Nishida, Junko; Aoki, Aya; Inoue, Tatsuya; Yanagi, Yasuo] Univ Tokyo, Sch Med, Dept Ophthalmol, Bunkyo Ku, Tokyo 1138655, Japan.
C3 University of Tokyo
RP Yanagi, Y (通讯作者)，Univ Tokyo, Sch Med, Dept Ophthalmol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM yanagi-tky@umin.ac.jp
RI Yanagi, Yasuo/AAA-5441-2022; Takahashi, Hidenori/H-2945-2019; Yanagi,
   Yasuo/AAF-2670-2020
OI Takahashi, Hidenori/0000-0001-5331-4730; Yanagi,
   Yasuo/0000-0002-0362-7285
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NR 38
TC 2
Z9 2
U1 0
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2015
VL 131
BP 77
EP 83
DI 10.1016/j.exer.2015.01.005
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CA5VA
UT WOS:000348974700009
PM 25576666
DA 2022-11-30
ER

PT J
AU Caputo, M
   Zirpoli, H
   Di Benedetto, R
   De Nadai, K
   Tecce, MF
AF Caputo, M.
   Zirpoli, H.
   Di Benedetto, R.
   De Nadai, K.
   Tecce, M. F.
TI Perspectives of Choroidal Neovascularization Therapy
SO CURRENT DRUG TARGETS
LA English
DT Review
DE Choroidal neovascularization; macular degeneration; diagnostics;
   targeted therapies
ID PIGMENT EPITHELIAL-CELLS; REGULATED GENE-EXPRESSION; MACULAR
   DEGENERATION; PHOTODYNAMIC THERAPY; BISPECIFIC ANTIBODIES; OCULAR
   ANGIOGENESIS; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; UVEAL MELANOMA; DRUG
   DISCOVERY
AB Vision loss secondary to Choroidal Neovascularization (CNV) is becoming a major disease condition in the developed world. CNV is typically secondary to Age-related Macular Degeneration (AMD) and these conditions are major, and also substantially increasing, causes of blindness among aged people. Several therapeutic options are currently available to treat CNV with variable efficacy on disease progress. Among existing treatments there are laser photocoagulation, photodynamic therapies, local corticosteroids and, more recently, the use of anti-angiogenic factors. Although by these treatments very effective results are obtained and their further improvement is still possible, it is also reasonable and necessary to look for more successful and definitive alternatives. The research in this direction is already very active and it can be expected that applications of the more recent molecular technologies will bring important advances also for CNV. These will likely regard the use of gene therapy and of new target specific factors. Gene therapy methodologies are rapidly becoming closer to current clinical use and, since the eye is a particularly favorable organ for drug delivery, their ocular use is probably going to be among the first successful applications of these techniques. In addition to its specific technology, gene therapy requires the knowledge of specific genes to be modulated to adequately affect pathogenesis and progression of the disease for which it has to be applied. This will also be true for the use of novel target specific drugs such as antibodies and other molecules able to affect cellular factors and pathways also related to disease development. For this reason, a major direction of future CNV therapies will be the identification of specific gene, gene products, metabolic pathways and metabolites related to the disease. This information, in addition to be suitable for gene and target specific therapies, will also allow the development of new procedures to improve diagnosis and/or prognostic evaluation of the disease.
C1 [Caputo, M.; Zirpoli, H.; Tecce, M. F.] Univ Salerno, Dipartimento Sci Farmaceut, I-84084 Fisciano, SA, Italy.
   [Di Benedetto, R.] ASL NA 1, Dipartimento Prevenz, Naples, Italy.
   [De Nadai, K.] Univ Ferrara, Dipartimento Discipline Medchirurg Comunicaz & Co, Sez Oculist, I-44100 Ferrara, Italy.
C3 University of Salerno; University of Ferrara
RP Tecce, MF (通讯作者)，Univ Salerno, Dipartimento Sci Farmaceut, Via Ponte Don Melillo, I-84084 Fisciano, SA, Italy.
EM tecce@unisa.it
RI Tecce, Mario Felice/L-7295-2013
OI TECCE, Mario Felice/0000-0003-2355-6047
FU University of Salerno
FX The authors acknowledge the financial support from the University of
   Salerno FARB 2007 and VII PhD Program in Biochemistry and Pathology of
   Drug Action grants.
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NR 80
TC 10
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U2 10
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1389-4501
J9 CURR DRUG TARGETS
JI Curr. Drug Targets
PD FEB
PY 2011
VL 12
IS 2
BP 234
EP 242
DI 10.2174/138945011794182791
PG 9
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 720RX
UT WOS:000287299000011
PM 20887238
DA 2022-11-30
ER

PT J
AU Rotsos, T
   Sagoo, MS
   daCruz, L
   Andrews, R
   Dowler, J
AF Rotsos, T.
   Sagoo, M. S.
   daCruz, L.
   Andrews, R.
   Dowler, J.
TI Intravitreal anti-VEGF treatment in eyes with combined choroidal
   neovascularisation and vitreomacular traction syndrome
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; POSTERIOR VITREOUS DETACHMENT; MACULAR
   DEGENERATION; VITREORETINAL ADHESIONS; RANIBIZUMAB; RESOLUTION; THERAPY
AB Purpose To report the effect of intravitreal anti-vascular endothelial growth factor injections (IVI) on visual acuity in eyes with choroidal neovascularisation (CNVM) and co-existent vitreomacular traction (VMT) or when VMT has developed during the course of treatment.
   Methods Retrospective interventional case series of seven eyes in seven patients. VMT was monitored with serial optical coherence tomography scans.
   Results The mean age at presentation was 74 years (range 64-95 years). All patients presented with blurring of central vision, rather than distortion. The aetiology of CNVM was wet age-related macular degeneration in five eyes (72%), angioid streaks in one eye (14%) and pathological myopia in one eye (14%). Ranibizumab was used in four eyes (57%) and bevacizumab in three (43%) for the active CNVM component. The mean follow-up was 11 months (range 2-28 months). None of the eyes in this series required surgery for the VMT component, nor were there any cases of spontaneous resolution of VMT. Visual acuity was stabilised or improved in five of the seven eyes (71%) with IVI. Visual acuity results across the whole group were gain of three or more lines of Snellen visual acuity in two eyes (28%), gain of up to three lines in three eyes (42%), no change in visual acuity in one eye (14%) and loss of up to three lines in one eye (14%). There were no eyes losing more than three lines of Snellen visual acuity. In four eyes with pre-existing VMT, visual acuity improved in three with IVI. In three eyes that developed VMT after IVI, visual acuity improved in two with IVI. Delay from diagnosis of CNVM to treatment with IVI contributed to a poor response.
   Conclusions Most eyes improved visual acuity with IVI for combined CNVM and VMT. Despite the often dramatic features of VMT on optical coherence tomography, treatment of co-existing CNVM should be prompt. Vitreoretinal surgery was not required in this series, but is held in reserve if there is still potential for gain in vision following CNVM resolution.
C1 [Rotsos, T.; Sagoo, M. S.; daCruz, L.; Andrews, R.; Dowler, J.] Moorfields Eye Hosp, Med Retina Serv, London EC1V 2PD, England.
   [Sagoo, M. S.] UCL Inst Ophthalmol, London, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London
RP Sagoo, MS (通讯作者)，Moorfields Eye Hosp, Med Retina Serv, City Rd, London EC1V 2PD, England.
EM mandeep.sagoo@moorfields.nhs.uk
OI Sagoo, Mandeep/0000-0003-1530-3824
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NR 28
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PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD SEP
PY 2010
VL 94
IS 9
BP 1205
EP 1210
DI 10.1136/bjo.2009.173765
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 654YF
UT WOS:000282206500020
PM 20558421
DA 2022-11-30
ER

PT J
AU Li, DL
   Zhang, JX
   Liu, ZJ
   Gong, YY
   Zheng, Z
AF Li, Dongli
   Zhang, Junxiu
   Liu, Zijia
   Gong, Yuanyuan
   Zheng, Zhi
TI Human umbilical cord mesenchymal stem cell-derived exosomal miR-27b
   attenuates subretinal fibrosis via suppressing epithelial-mesenchymal
   transition by targeting HOXC6
SO STEM CELL RESEARCH & THERAPY
LA English
DT Article
DE Epithelial-mesenchymal transition; Exosomes; Subretinal fibrosis;
   Mesenchymal stem cells
ID VESICLES PROMOTE NEUROPROTECTION; RETINAL LASER INJURY; EXTRACELLULAR
   VESICLES; MACULAR DEGENERATION; BONE-MARROW
AB Background and aimSubretinal fibrosis resulting from neovascular age-related macular degeneration (nAMD) is one of the major causes of serious and irreversible vision loss worldwide, and no definite and effective treatment exists currently. Retinal pigmented epithelium (RPE) cells are crucial in maintaining the visual function of normal eyes and its epithelial-mesenchymal transition (EMT) is associated with the pathogenesis of subretinal fibrosis. Stem cell-derived exosomes have been reported to play a crucial role in tissue fibrosis by transferring their molecular contents. This study aimed to explore the effects of human umbilical cord-derived mesenchymal stem cell exosomes (hucMSC-Exo) on subretinal fibrosis in vivo and in vitro and to investigate the anti-fibrotic mechanism of action of hucMSC-Exo.MethodsIn this study, human umbilical cord-derived mesenchymal stem cells (hucMSCs) were successfully cultured and identified, and exosomes were isolated from the supernatant by ultracentrifugation. A laser-induced choroidal neovascularization (CNV) and subretinal fibrosis model indicated that the intravitreal administration of hucMSC-Exo effectively alleviated subretinal fibrosis in vivo. Furthermore, hucMSC-Exo could efficaciously suppress the migration of retinal pigmented epithelial (RPE) cells and promote the mesenchymal-epithelial transition by delivering miR-27b-3p. The latent binding of miR-27b-3p to homeobox protein Hox-C6 (HOXC6) was analyzed by bioinformatics prediction and luciferase reporter assays.ResultsThis study showed that the intravitreal injection of hucMSC-Exo effectively ameliorated laser-induced CNV and subretinal fibrosis via the suppression of epithelial-mesenchymal transition (EMT) process. In addition, hucMSC-Exo containing miR-27b repressed the EMT process in RPE cells induced by transforming growth factor-beta2 (TGF-beta 2) via inhibiting HOXC6 expression.ConclusionsThe present study showed that HucMSC-derived exosomal miR-27b could reverse the process of EMT induced by TGF-beta 2 via inhibiting HOXC6, indicating that the exosomal miR-27b/HOXC6 axis might play a vital role in ameliorating subretinal fibrosis. The present study proposed a promising therapeutic agent for treating ocular fibrotic diseases and provided insights into the mechanism of action of hucMSC-Exo on subretinal fibrosis.
C1 [Li, Dongli; Zhang, Junxiu; Liu, Zijia; Gong, Yuanyuan; Zheng, Zhi] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Ophthalmol, Sch Med, Shanghai 20080, Peoples R China.
   [Li, Dongli; Zhang, Junxiu; Liu, Zijia; Gong, Yuanyuan; Zheng, Zhi] Natl Clin Res Ctr Eye Dis, Shanghai 200080, Peoples R China.
   [Li, Dongli; Zhang, Junxiu; Liu, Zijia; Gong, Yuanyuan; Zheng, Zhi] Shanghai Key Lab Ocular Fundus Dis, Shanghai 200080, Peoples R China.
   [Li, Dongli; Zhang, Junxiu; Liu, Zijia; Gong, Yuanyuan; Zheng, Zhi] Shanghai Engn Ctr Visual Sci & Photomed, 100 Haining Rd, Shanghai 200080, Peoples R China.
C3 Shanghai Jiao Tong University
RP Gong, YY; Zheng, Z (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Ophthalmol, Sch Med, Shanghai 20080, Peoples R China.; Gong, YY; Zheng, Z (通讯作者)，Natl Clin Res Ctr Eye Dis, Shanghai 200080, Peoples R China.; Gong, YY; Zheng, Z (通讯作者)，Shanghai Key Lab Ocular Fundus Dis, Shanghai 200080, Peoples R China.; Gong, YY; Zheng, Z (通讯作者)，Shanghai Engn Ctr Visual Sci & Photomed, 100 Haining Rd, Shanghai 200080, Peoples R China.
EM gyydr@alumni.sjtu.edu.cn; zhengzhi139@163.com
FU National Key R&D Program of China [2016YFC0904800, 2019YFC0840607];
   National Science and Technology Major Project of China [2017ZX09304010];
   Shanghai Science and Technology Commission Research Project
   [19401932700]; Clinical Research Innovation Plan of Shanghai General
   Hospital [CTCCR-2018BP04]; Bethune Lumitin Research Funding for the
   young and middle-aged Ophthalmologists [BJ-LM2016003J]
FX This work was supported by the National Key R&D Program of China (grant
   nos. 2016YFC0904800, 2019YFC0840607), National Science and Technology
   Major Project of China (grant nos. 2017ZX09304010), Shanghai Science and
   Technology Commission Research Project (grant nos.19401932700), Clinical
   Research Innovation Plan of Shanghai General Hospital (grant nos.
   CTCCR-2018BP04), and Bethune Lumitin Research Funding for the young and
   middle-aged Ophthalmologists (BJ-LM2016003J).
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NR 44
TC 13
Z9 13
U1 1
U2 7
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1757-6512
J9 STEM CELL RES THER
JI Stem Cell Res. Ther.
PD JAN 7
PY 2021
VL 12
IS 1
AR 24
DI 10.1186/s13287-020-02064-0
PG 17
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA PU7RY
UT WOS:000609499600014
PM 33413548
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Hughes, S
   Gumas, J
   Lee, R
   Rumano, M
   Berger, N
   Gautam, AK
   Sfyroera, G
   Chan, AL
   Gnanaguru, G
   Connor, KM
   Kim, BJ
   Dunaief, JL
   Ricklin, D
   Hajishengallis, G
   Yancopoulou, D
   Reis, ES
   Mastellos, DC
   Lambris, JD
AF Hughes, Sarah
   Gumas, Justin
   Lee, Rebecca
   Rumano, Merita
   Berger, Nadja
   Gautam, Avneesh Kumar
   Sfyroera, Georgia
   Chan, Anna Lorena
   Gnanaguru, Gopalan
   Connor, Kip M.
   Kim, Benjamin J.
   Dunaief, Joshua L.
   Ricklin, Daniel
   Hajishengallis, George
   Yancopoulou, Despina
   Reis, Edimara S.
   Mastellos, Dimitrios C.
   Lambris, John D.
TI Prolonged intraocular residence and retinal tissue distribution of a
   fourth-generation compstatin-based C3 inhibitor in non-human primates
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE Complement C3 inhibitors; Compstatins; Cp40-KKK; Retina; Macular
   degeneration; Geographic atrophy; Ocular pharmacokinetics; Nonhuman
   primates
ID MACULAR DEGENERATION; COMPLEMENT; ACTIVATION; CP40
AB Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly population. Genetic studies in susceptible individuals have linked this ocular disease to deregulated complement activity that culminates in increased C3 turnover, retinal inflammation and photoreceptor loss. Therapeutic targeting of C3 has therefore emerged as a promising strategy for broadly intercepting the detrimental proinflammatory consequences of complement activation in the retinal tissue. In this regard, a PEGylated second-generation derivative of the compstatin family of C3-targeted inhibitors is currently in late-stage clinical development as a treatment option for geographic atrophy, an advanced form of AMD which lacks approved therapy. While efficacy has been strongly suggested in phase 2 clinical trials, crucial aspects still remain to be defined with regard to the ocular bioavailability, tissue distribution and residence, and dosing frequency of such inhibitors in AMD patients. Here we report the intraocular distribution and pharmacokinetic profile of the fourth-generation compstatin analog, Cp40-KKK in cynomolgus monkeys following a single intravitreal injection. Using a sensitive surface plasmon resonance (SPR)-based competition assay and ELISA, we have quantified both the amount of inhibitor and the concentration of C3 retained in the vitreous of Cp40-KKK-injected animals. Cp40-KKK displays prolonged intraocular residence, being detected at C3-saturating levels for over 3 months after a single intravitreal injection. Moreover, we have probed the distribution of Cp40-KKK within the ocular tissue by means of immunohistochemistry and highly specific anti-Cp40-KKK antibodies. Both C3 and Cp40-KKK were detected in the retinal tissue of inhibitor-injected animals, with prominent co-localization in the choroid one-month post intravitreal injection. These results attest to the high retinal tissue penetrance and target-driven distribution of Cp40-KKK. Given its subnanomolar binding affinity and prolonged ocular residence, Cp40-KKK constitutes a promising drug candidate for ocular pathologies underpinned by deregulated C3 activation.
C1 [Hughes, Sarah; Gumas, Justin; Lee, Rebecca; Rumano, Merita; Berger, Nadja; Gautam, Avneesh Kumar; Sfyroera, Georgia; Reis, Edimara S.; Lambris, John D.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Chan, Anna Lorena] Jose R Reyes Mem Med Ctr, Manila, Philippines.
   [Gnanaguru, Gopalan; Connor, Kip M.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis Lab, Boston, MA 02114 USA.
   [Gnanaguru, Gopalan; Connor, Kip M.] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA.
   [Kim, Benjamin J.; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Ricklin, Daniel] Univ Basel, Dept Pharmaceut Sci, Basel, Switzerland.
   [Hajishengallis, George] Univ Penn, Dept Basic & Translat Sci, Penn Dent Med, Philadelphia, PA 19104 USA.
   [Yancopoulou, Despina] Amyndas Pharmaceut, Glifadha, Greece.
   [Mastellos, Dimitrios C.] Natl Ctr Sci Res Demokritos, Athens, Greece.
C3 University of Pennsylvania; Pennsylvania Medicine; Harvard University;
   Massachusetts Eye & Ear Infirmary; Harvard University; Harvard Medical
   School; University of Pennsylvania; Pennsylvania Medicine; University of
   Basel; University of Pennsylvania; National Centre of Scientific
   Research "Demokritos"
RP Lambris, JD (通讯作者)，Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA.; Mastellos, DC (通讯作者)，Natl Ctr Sci Res Demokritos, Athens, Greece.
EM mastellos@rrp.demokritos.gr; lambris@pennmedicine.upenn.edu
RI Gnanaguru, Gopalan/AAJ-9336-2021; Gautam, Avneesh/AAU-3804-2021
OI Gautam, Avneesh/0000-0003-1745-5530; Mastellos,
   Dimitrios/0000-0002-6634-3271; Berger, Nadja/0000-0002-4435-8317
FU U.S. National Institutes of Health [AI068730]; Operational Programme
   "Competitiveness, Entrepreneurship and Innovation" (NSRF 2014-2020) [MIS
   5002559]; European Union (European Regional Development Fund)
FX We thank Prof. Ronald P. Taylor (University of Virginia) for generously
   providing the anti-C3b/iC3b monoclonal antibody, D131-45A8E11, for
   intravitreal C3 measurements. This work was supported by grants from the
   U.S. National Institutes of Health (AI068730; to JDL). DCM acknowledges
   support from project MIS 5002559 which is implemented under the "Action
   for the Strategic Development on the Research and Technological Sector",
   funded by the Operational Programme "Competitiveness, Entrepreneurship
   and Innovation" (NSRF 2014-2020) and co-financed by Greece and the
   European Union (European Regional Development Fund.
CR Berger N, 2018, J MED CHEM, V61, P6153, DOI 10.1021/acs.jmedchem.8b00560
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NR 27
TC 6
Z9 6
U1 2
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
EI 1521-7035
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD MAY
PY 2020
VL 214
AR 108391
DI 10.1016/j.clim.2020.108391
PG 8
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA LK2MA
UT WOS:000530692800019
PM 32229292
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Ye, Z
   He, SZ
   Li, ZH
AF Ye, Zi
   He, Shou-Zhi
   Li, Zhao-Hui
TI Effect of A beta protein on inhibiting proliferation and promoting
   apoptosis of retinal pigment epithelial cells
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE amyloid beta protein; retinal pigment epithelial cells; proliferation;
   apoptosis; receptor for advanced glycation endproducts; nuclear
   factor-kappaB; age-related macular degeneration
ID NF-KAPPA-B; MACULAR DEGENERATION; ALZHEIMERS-DISEASE; INFLAMMASOME
   ACTIVATION; OXIDATIVE STRESS; AMYLOID-BETA; EXPRESSION; INCREASES;
   DRUSEN; MODEL
AB AIM: To identify the effect and regulatory mechanism of amyloid beta (A beta) protein on retinal pigment epithelial (RPE) cells in cell proliferation and apoptosis, and clarify A beta role in the pathogenesis of age-related macular degeneration (AMD).
   METHODS: The model of A beta 25-35 protein cytotoxicity in RPE cell was successfully established to investigate the effect of A beta protein on RPE cells in vitro. Based on A beta protein, the specific inhibitors (HY-50682 or BAY11-7082) or activating agent (lipopolysaccharide) was used to analyze the regulatory mechanism of A beta protein to RPE cells on cell proliferation and apoptosis by flow cytometry, real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay and dual-luciferase reporter gene assay.
   RESULTS: The number of RPE cells, treated with A beta 25-35 from 0.3 to 60 mu mol/L, significantly reduce (P<0.01), and had the dose-dependent effect. A beta protein 60 mu mol/L inhibits the G1/S phase transition (P<0.01) and down-regulated cyclin E mRNA level (P<0.01). Similarly, A beta 25-35 induced a significant increase of cell apoptosis, accompanied by the significantly higher level of activated caspase 3 protein. Furthermore, nuclear factor-kappaB (NF-kappa B) activity and phosphorylated I kappa-Ba level would significantly lower in treated RPE cells. Using specific inhibitors or activating agent based on the A beta, the cell numbers, NF-kappa B activity, phosphorylated I kappa-Ba level, receptor for advanced glycation endproducts (RAGE) gene expression levels, cyclin E mRNA level and activated caspase 3 level had accordingly changed by different methods, confirming that RAGE/NF-kappa B signaling pathway involved in the regulation of A beta protein on RPE cell apoptosis and proliferation.
   CONCLUSION: A beta protein inhibits cell proliferation and activates apoptosis via inactivation of the RAGE/NF-kappa B signaling pathway in RPE cell.
C1 [Ye, Zi; He, Shou-Zhi; Li, Zhao-Hui] Chinese Peoples Liberat Army Gen Hosp, Dept Ophthalmol, Beijing 100853, Peoples R China.
C3 Chinese People's Liberation Army General Hospital
RP Li, ZH (通讯作者)，Chinese Peoples Liberat Army Gen Hosp, Dept Ophthalmol, Beijing 100853, Peoples R China.
EM zhaohuili650@hotmail.com
RI Zi, Ye/GWM-3932-2022
OI Li, Zhaohui/0000-0002-4132-658X
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NR 20
TC 5
Z9 6
U1 0
U2 3
PU IJO PRESS
PI XI AN
PA NO 269 YOUYI EAST RD, XI AN, 710054, PEOPLES R CHINA
SN 2222-3959
EI 2227-4898
J9 INT J OPHTHALMOL-CHI
JI Int. J. Ophthalmol.
PD JUN 18
PY 2018
VL 11
IS 6
BP 929
EP 934
DI 10.18240/ijo.2018.06.06
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GM0BY
UT WOS:000437711600006
PM 29977803
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Yan, ZZ
   Shi, HH
   Zhu, RR
   Li, LL
   Qin, B
   Kang, LH
   Chen, H
   Guan, HJ
AF Yan, Zhenzhen
   Shi, Haihong
   Zhu, Rongrong
   Li, Lele
   Qin, Bai
   Kang, Lihua
   Chen, Hui
   Guan, Huaijin
TI Inhibition of YAP ameliorates choroidal neovascularization via
   inhibiting endothelial cell proliferation
SO MOLECULAR VISION
LA English
DT Article
ID HIPPO SIGNALING PATHWAY; TISSUE TRANSGLUTAMINASE; GROWTH-FACTOR;
   ANGIOGENESIS; PROTEIN; MOUSE; RANIBIZUMAB; HOMEOSTASIS; ACTIVATION;
   EXPRESSION
AB Purpose: Age-related macular degeneration (AMD) is the leading cause of central visual loss among patients over the age of 55 years worldwide. Neovascular-type AMD (nAMD) accounts for approximately 10% of patients with AMD and is characterized by choroidal neovascularization (CNV). The proliferation of choroidal endothelial cells (CECs) is one important step in the formation of new vessels. Transcriptional coactivator Yes-associated protein (YAP) can promote the proliferation of multiple cancer cells, corneal endothelial cells, and vascular smooth muscle cells, which participate in angiogenesis. This study intends to reveal the expression and functions of YAP during the CNV process.
   Methods: In the study, a mouse CNV model was generated by laser photocoagulation. YAP expression was detected with western blotting and immunohistochemistry. YAP siRNA and ranibizumab, a VEGF monoclonal antibody, were injected intravitreally in CNV mice. The YAP and VEGF expression levels after injection were detected with western blotting. The incidence and leakage area of CNV were measured with fundus fluorescein angiography, choroidal flat mounting, and hematoxylin and eosin (HE) staining. Immunofluorescent double staining was used to detect YAP cellular localization with CD31 (an endothelial cell marker) antibody. Proliferating cell nuclear antigen (PCNA) expression in CNV mice without or with YAP siRNA intravitreal injection and the colocalization of PCNA and CD31 were measured with western blotting and immunofluorescent double staining, respectively.
   Results: YAP expression increased following laser exposure, in accordance with vascular endothelial growth factor (VEGF) expression. YAP siRNA and ranibizumab decreased VEGF expression and the incidence and leakage area of CNV. YAP was localized in the vascular endothelium within the CNV site. Additionally, after laser exposure, YAP siRNA inhibited the increased expression of PCNA, which was colocalized with endothelial cells.
   Conclusions: This study showed that YAP upregulation promoted CNV formation by upregulating the proliferation of endothelial cells, providing evidence for the molecular mechanisms of CNV and suggesting a novel molecular target for nAMD treatment.
C1 [Yan, Zhenzhen; Shi, Haihong; Zhu, Rongrong; Li, Lele; Qin, Bai; Kang, Lihua; Chen, Hui; Guan, Huaijin] Affiliated Hosp Nantong Univ, Dept Ophthalmol, Nantong 226001, Jiangsu, Peoples R China.
C3 Nantong University
RP Guan, HJ (通讯作者)，Affiliated Hosp Nantong Univ, Dept Ophthalmol, Nantong 226001, Jiangsu, Peoples R China.
EM guanhjeye@163.com
FU National Natural Science Foundation of China [81470616]
FX The study was supported by National Natural Science Foundation of China
   (No. 81470616).
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NR 65
TC 19
Z9 19
U1 2
U2 8
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JAN 31
PY 2018
VL 24
BP 83
EP 93
PG 11
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA FU3RJ
UT WOS:000423769100001
PM 29422766
DA 2022-11-30
ER

PT J
AU Rokicki, W
   Drozdzowska, B
   Czekajlo, A
   Grzeszczak, W
   Karpe, J
   Wiktor, K
   Pluskiewicz, W
AF Rokicki, Wojciech
   Drozdzowska, Bogna
   Czekajlo, Aleksandra
   Grzeszczak, Wladyslaw
   Karpe, Jacek
   Wiktor, Katarzyna
   Pluskiewicz, Wojciech
TI Common ophthalmic problems of urban and rural postmenopausal women in a
   population sample of Raciborz district, a RAC-OST-POL Study
SO ANNALS OF AGRICULTURAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
DE Epidemiological study; women; vision; rural; urban
ID HORMONE REPLACEMENT THERAPY; AGE-RELATED MACULOPATHY; DRY EYE;
   REPRODUCTIVE EXPOSURES; MACULAR DEGENERATION; PREVALENCE; CATARACT;
   ASSOCIATION; PRESSURE; GLAUCOMA
AB Introduction and objective. We wished to establish the prevalence of eye diseases and eye disease risk factors at postmenopausal age and to compare ophthalmic problems in urban and rural areas of Raciborz.
   Patients and methods. The study was performed in 2010. Out of the whole population of Raciborz, Poland, 10 percent (1750) of women were randomly selected for the reported study. Finally, ocular diseases, ophthalmic agents, health status (physical activity level, body mass index-BMI, reproductive history, the use of psychotropic drugs and hormone replacement therapy-HRT) were recorded in 623 women. The women underwent visual acuity test and anterior segment examination, applanation tonometry and indirect ophthalmoscopy.
   Results. The mean age of the selected patients was 66.01 +/- 7.76 years, 275 (44%) of them originating from rural and 348(56%) from urban regions. The average woman was obese (BMI=30.54 +/- 5.38 kg/m(2)), with near normal agility and reproductive history of 2.59 +/- 1.55 births, 147(24%) subjects remained under regular HRT support. According to the WHO, the visual acuity was classified as normal or near normal in 87.5%, while no blindness was recorded at all. Visual acuity depended, first of all, on lens status and was better among subjects with good agility (R=-0.31, p=0.001). Dry eye prevalence increased significantly over age of 67 years (p=0.000) and HRT seemed to be a dry eye protective factor (p=0.010). Except age, No other risk factors of cataract, other than age, were identified. Normal agility (p=0.003) and HRT (p=0.032) were associated with lower AMD (age-related macular degeneration) prevalence rates. The differences between urban and rural participants were presented only in education, reproductive history, hypertension and frequency of ophthalmic examinations.
   Conclusions. Older adult women living in neighboring urban and rural areas present no differential in ophthalmic health problems.
C1 [Rokicki, Wojciech] Med Univ Silesia, Dept & Clin Ophthalmol, Katowice, Poland.
   [Drozdzowska, Bogna] Med Univ Silesia, Dept Pathomorphol, Katowice, Poland.
   [Czekajlo, Aleksandra] Dept Nephrol, Raciborz, Poland.
   [Grzeszczak, Wladyslaw] Med Univ Silesia, Dept & Clin Internal Dis Diabetol & Nephrol, Katowice, Poland.
   [Karpe, Jacek] Med Univ Silesia, Dept Anaesthesiol & Intens Care, Katowice, Poland.
   [Wiktor, Katarzyna] KCR SA, Warsaw, Poland.
   [Pluskiewicz, Wojciech] Med Univ Silesia, Dept & Clin Internal Dis Diabetol & Nephrol, Metab Bone Dis Unit, Katowice, Poland.
C3 Medical University Silesia; Medical University Silesia; Medical
   University Silesia; Medical University Silesia; Medical University
   Silesia
RP Rokicki, W (通讯作者)，Med Univ Silesia, Dept Ophthalmol, Katowice, Poland.
EM wrjr@xl.wp.pl
OI Pluskiewicz, Wojciech/0000-0003-1839-6560; Drozdzowska,
   Bogna/0000-0002-2287-6842; Grzeszczak, Wladyslaw/0000-0003-1947-3783;
   Karpe, Jacek/0000-0003-0578-2497
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NR 30
TC 7
Z9 7
U1 0
U2 6
PU INST AGRICULTURAL MEDICINE
PI LUBLIN
PA JACZEWSKIEGO 2, PO BOX 185, 20-950 LUBLIN, POLAND
SN 1232-1966
EI 1898-2263
J9 ANN AGR ENV MED
JI Ann. Agr. Env. Med.
PY 2014
VL 21
IS 1
BP 70
EP 74
PG 5
WC Environmental Sciences; Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health
GA AE3HO
UT WOS:000333867800013
PM 24738500
DA 2022-11-30
ER

PT J
AU Hu, ZH
   Medioni, GG
   Hernandez, M
   Hariri, A
   Wu, XD
   Sadda, SR
AF Hu, Zhihong
   Medioni, Gerard G.
   Hernandez, Matthias
   Hariri, Amirhossein
   Wu, Xiaodong
   Sadda, SriniVas R.
TI Segmentation of the Geographic Atrophy in Spectral-Domain Optical
   Coherence Tomography and Fundus Autofluorescence Images
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE segmentation; geographic atrophy; spectral-domain optical coherence
   tomography images; fundus autofluorescence images
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; SHAPE
AB PURPOSE. Geographic atrophy (GA) is the atrophic late-stage manifestation of age-related macular degeneration (AMD), which may result in severe vision loss and blindness. The purpose of this study was to develop a reliable, effective approach for GA segmentation in both spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) images using a level set-based approach and to compare the segmentation performance in the two modalities.
   METHODS. To identify GA regions in SD-OCT images, three retinal surfaces were first segmented in volumetric SD-OCT images using a double-surface graph search scheme. A two-dimensional (2-D) partial OCT projection image was created from the segmented choroid layer. A level set approach was applied to segment the GA in the partial OCT projection image. In addition, the algorithm was applied to FAF images for the GA segmentation. Twenty randomly chosen macular SD-OCT (Zeiss Cirrus) volumes and 20 corresponding FAF (Heidelberg Spectralis) images were obtained from 20 subjects with GA. The algorithm-defined GA region was compared with consensus manual delineation performed by certified graders.
   RESULTS. The mean Dice similarity coefficients (DSC) between the algorithm-and manually defined GA regions were 0.87 +/- 0.09 in partial OCT projection images and 0.89 +/- 0.07 in registered FAF images. The area correlations between them were 0.93 (P < 0.001) in partial OCT projection images and 0.99 (P < 0.001) in FAF images. The mean DSC between the algorithm-defined GA regions in the partial OCT projection and registered FAF images was 0.79 +/- 0.12, and the area correlation was 0.96 (P < 0.001).
   CONCLUSIONS. A level set approach was developed to segment GA regions in both SD-OCT and FAF images. This approach demonstrated good agreement between the algorithm-and manually defined GA regions within each single modality. The GA segmentation in FAF images performed better than in partial OCT projection images. Across the two modalities, the GA segmentation presented reasonable agreement.
C1 [Hu, Zhihong; Hariri, Amirhossein; Sadda, SriniVas R.] Univ So Calif, Doheny Eye Inst, Los Angeles, CA USA.
   [Medioni, Gerard G.; Hernandez, Matthias] Univ So Calif, Dept Comp Sci, Los Angeles, CA 90089 USA.
   [Wu, Xiaodong] Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA.
C3 Doheny Eye Institute; University of Southern California; University of
   Southern California; University of Iowa
RP Sadda, SR (通讯作者)，Doheny Eye Inst, 1450 San Pablo St, Los Angeles, CA 90033 USA.
EM ssadda@doheny.org
FU Beckman Macular Degeneration Research Center; Research to Prevent
   Blindness Physician Scientist Award; Division of Computing and
   Communication Foundations [0844765] Funding Source: National Science
   Foundation
FX Supported by the Beckman Macular Degeneration Research Center and a
   Research to Prevent Blindness Physician Scientist Award.
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NR 19
TC 49
Z9 50
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2013
VL 54
IS 13
BP 8375
EP 8383
DI 10.1167/iovs.13-12552
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AD1ZM
UT WOS:000333032200033
PM 24265015
DA 2022-11-30
ER

PT J
AU Kennedy, RD
   Spafford, MM
   Behm, I
   Hammond, D
   Fong, GT
   Borland, R
AF Kennedy, Ryan David
   Spafford, Marlee M.
   Behm, Ilan
   Hammond, David
   Fong, Geoffrey T.
   Borland, Ron
TI Positive impact of Australian 'blindness' tobacco warning labels:
   findings from the ITC four country survey
SO CLINICAL AND EXPERIMENTAL OPTOMETRY
LA English
DT Article
DE age-related macular degeneration; cessation; health education; public
   health; smoking
ID AGE-RELATED MACULOPATHY; SMOKING-CESSATION; UNITED-KINGDOM
AB Background: Smokers with greater knowledge of the health effects of smoking are more likely to quit and remain abstinent. Australia has communicated the causal association of smoking and blindness since the late 1990s. In March 2007, Australia became the first country to include a pictorial warning label on cigarette packages with the message that smoking causes blindness. The current study tested the hypothesis that the introduction of this warning label increased smokers' knowledge of this important health effect.
   Methods: Six waves of the International Tobacco Control Four Country Survey were conducted, as a telephone survey of 17,472 adult smokers in Australia, Canada, United Kingdom and the United States, with three waves before and three waves after the blindness health warning was introduced in Australia. The survey measured adult smokers' knowledge that smoking causes blindness.
   Results: Australian smokers were significantly more likely to report that smoking causes blindness, compared to Canadian, UK and US smokers, where there were neither health campaigns nor health warnings labels about blindness. After the introduction of the blindness warning, Australian smokers were more likely than before the blindness warning to report that they know that smoking causes blindness (62 versus 49 per cent; OR = 1.68, 95% CI: 1.03, 2.76, p = 0.04). In Australia, smokers aged over 55?years were less likely than those aged 18 to 24 to report that smoking causes blindness (OR = 0.43; 95% CI: 0.29, 0.62, p < 0.001).
   Conclusion: While more smokers report that smoking causes blindness in Australia compared to other countries, which have not had national social marketing campaigns, further gains in knowledge were found after pictorial warning labels were introduced in Australia. Findings suggest there is still a need to educate the public about the causal association of smoking and blindness. More education may be needed to redress the knowledge gap in older Australian smokers as the incidence of age-related macular degeneration increases with age.
C1 [Kennedy, Ryan David] Univ Waterloo, Propel Ctr Populat Hlth Impact, Waterloo, ON N2L 3G1, Canada.
   [Kennedy, Ryan David; Behm, Ilan] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
   [Spafford, Marlee M.] Univ Waterloo, Sch Optometry & Vis Sci, Waterloo, ON N2L 3G1, Canada.
   [Hammond, David] Univ Waterloo, Sch Publ Hlth & Hlth Syst, Waterloo, ON N2L 3G1, Canada.
   [Fong, Geoffrey T.] Univ Waterloo, Dept Psychol, Waterloo, ON N2L 3G1, Canada.
   [Fong, Geoffrey T.] Ontario Inst Canc Res, Toronto, ON, Canada.
   [Borland, Ron] Canc Council Victoria, Carlton, Vic, Australia.
C3 University of Waterloo; Harvard University; Harvard T.H. Chan School of
   Public Health; University of Waterloo; University of Waterloo;
   University of Waterloo; Ontario Institute for Cancer Research;
   University of Toronto; University Toronto Affiliates; Cancer Council
   Victoria
RP Kennedy, RD (通讯作者)，Univ Waterloo, Propel Ctr Populat Hlth Impact, Waterloo, ON N2L 3G1, Canada.
EM rdkennedy@uwaterloo.ca
RI Fong, Geoffrey T/H-2810-2014; Kennedy, Ryan David/U-3794-2017
OI Fong, Geoffrey T/0000-0001-9098-6472; Kennedy, Ryan
   David/0000-0002-9448-5234; Borland, Ron/0000-0003-0059-178X
FU National Health and Medical Research Council of Australia [265903,
   450110]; Commonwealth Department of Health and Ageing; Canadian
   Institutes for Health Research [57897, 79551, 115016]; U.S. National
   Cancer Institute [P50 CA111236, RO1 CA100362]; Robert Wood Johnson
   Foundation [045734]; Cancer Research UK [C312/A3726, C312/A6465,
   C312/A11039, C312/A11943]; Ontario Institute for Cancer Research;
   Canadian Cancer Society through the Propel Centre for Population Health
   Impact; Canadian Institutes of Health Research; Canadian Cancer Society
   Research Institute Junior Investigator Award; NATIONAL CANCER INSTITUTE
   [P50CA111236, R01CA100362] Funding Source: NIH RePORTER
FX Funding support for the ITC Four Country Survey was provided by the
   National Health and Medical Research Council of Australia (265903 and
   450110), Commonwealth Department of Health and Ageing, Canadian
   Institutes for Health Research (57897, 79551, and 115016), U.S. National
   Cancer Institute (P50 CA111236 and RO1 CA100362), Robert Wood Johnson
   Foundation (045734), Cancer Research UK (C312/A3726, C312/A6465,
   C312/A11039 and C312/A11943) and the Ontario Institute for Cancer
   Research (Senior Investigator Award). Additional support was provided
   from the Canadian Cancer Society through the Propel Centre for
   Population Health Impact and a Canadian Institutes of Health Research
   New Investigator Award and the Canadian Cancer Society Research
   Institute Junior Investigator Award (Hammond).
CR Australian Bureau of Statistics, NAT HLTH SURV SUMM R
   Australian Commonwealth Government, 2009, HLTH WARN CAMP 2006
   Australian Government Department of Health and Ageing, 2004, 1997 2003 NAT TOB CA
   Australian Government Department of Health and Ageing, TOB HLTH WARN 2011
   Australian Institute for Health and Welfare, 2005, B AIHW
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   ITC Four Country Survey Team, INT TOB CONTR POL EV
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NR 30
TC 24
Z9 24
U1 0
U2 9
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0816-4622
EI 1444-0938
J9 CLIN EXP OPTOM
JI Clin. Exp. Optom.
PD NOV
PY 2012
VL 95
IS 6
BP 590
EP 598
DI 10.1111/j.1444-0938.2012.00789.x
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 029IG
UT WOS:000310487500006
PM 22882362
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Munk, M
   Kiss, C
   Sulzbacher, F
   Eisenkolbl, S
   Sacu, S
   Kalcher, K
   Jampol, L
   Schmidt-Erfurth, U
AF Munk, Marion
   Kiss, Christopher
   Sulzbacher, Florian
   Eisenkoelbl, Stefan
   Sacu, Stefan
   Kalcher, Klaudius
   Jampol, Lee
   Schmidt-Erfurth, Ursula
TI Short-term progression of wet AMD and correlation with 1-year treatment
   results
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; neovascular AMD; pretreatment
   progression; short-term progression
AB . Purpose: Quantification of short-term progression of active neovascular age-related macular degeneration and correlation with 1-year outcome. Methods: Sixty-five patients with newly diagnosed treatment-naive active subfoveal choroidal neovascularization (CNV), who had participated in clinical trials testing anti-vascular endothelial growth factor therapy, were retrospectively assessed. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), Spectral Domain Optical Coherence Tomography (SD-OCT) and fluorescein angiography (FA) were performed twice during the pretreatment period. Changes in BCVA, central retinal thickness (CRT), average macular thickness (AMT) and leakage area were documented within this pretreatment period for all patients and for lesion type I (occult CNV, n = 42) and type II (classic CNV, n = 23). Three-month and 1-year BCVA were then correlated with the pretreatment period. Results: The pretreatment period was 19 +/- 3 days (range: 2108). Neither type I nor type II lesions showed a significant BCVA decrease or CRT/AMT increase during this period. On FA, mean leakage area increased significantly during the pretreatment period: in the pooled group from 5.50 +/- 0.62 (screening) to 7.60 +/- 0.86 mm2 (baseline) (p < 0.0001), in type II from 4.65 +/- 0.90 to 7.83 +/- 1.62 mm2 (p < 0.01) and in type I from 6.08 +/- 0.85 to 7.45 +/- 0.96 mm2 (p < 0.0001). The mean increase in leakage area per day was 0.046 +/- 0.02 mm2, p = 0.034. Type II showed a daily growth of 0.09 +/- 0.08 mm2 (p < 0.042) and type I 0.045 +/- 0.008 mm2 per day (p < 0.0001). However, neither leakage area increase nor pretreatment period was correlated with 3-month or 1-year BCVA outcome. Conclusions: SD-OCT and BCVA testing did not reveal deterioration during the pretreatment period. However, the leakage area progressed rapidly. Despite the rapid increasing leakage area, the 19-day waiting period was not associated with a poorer visual outcome at 3 months and 1 year.
C1 [Munk, Marion; Kiss, Christopher; Sulzbacher, Florian; Eisenkoelbl, Stefan; Sacu, Stefan; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria.
   [Kalcher, Klaudius] Univ Technol, Dept Stat & Probabil Theory, Vienna, Austria.
   [Jampol, Lee] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, Chicago, IL 60611 USA.
C3 Medical University of Vienna; Technische Universitat Wien; Northwestern
   University; Feinberg School of Medicine
RP Kiss, C (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM christopher.kiss@meduniwien.ac.at
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311; Kalcher,
   Klaudius/0000-0003-4558-7987
FU Alcon Laboratory Inc.; Bayer Health Care; Novartis; Regeneron; Pfizer
FX A part of this manuscript has been presented at the ARVO 2010. We like
   to thank Dr. Rene Ruckert for his continuous support and review of this
   manuscript, Dr. Wolfgang Huf and Dipl. Ing. Boubela for their continuous
   statistical support and Dr. Robert Blum for his medical writing
   assistance. Ursula Schmidt-Erfurth, MD, has following financial
   interests or relations to disclose: Consultant fees from Alcon
   Laboratory Inc., Bayer Health Care and Novartis, Lecture and travel fees
   from Alcon Laboratory Inc., Bayer Health Care, Novartis, Regeneron and
   Pfizer.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD SEP
PY 2012
VL 90
IS 6
BP e420
EP e427
DI 10.1111/j.1755-3768.2011.02353.x
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 996JB
UT WOS:000308079900001
PM 22339794
OA Bronze
DA 2022-11-30
ER

PT J
AU Bai, YY
   Ma, JX
   Guo, JJ
   Wang, JJ
   Zhu, M
   Chen, Y
   Le, YZ
AF Bai, Yanyan
   Ma, Jian-xing
   Guo, Junjing
   Wang, Juanjuan
   Zhu, Meili
   Chen, Ying
   Le, Yun-Zheng
TI Muller cell-derived VEGF is a significant contributor to retinal
   neovascularization
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE Muller cells; VEGF; ischaemia; neovascularization; neuron survival
ID ENDOTHELIAL GROWTH-FACTOR; PROLIFERATIVE DIABETIC-RETINOPATHY;
   OXYGEN-INDUCED RETINOPATHY; CRE RECOMBINASE; TRANSGENIC MICE; MOUSE
   MODEL; VASCULAR-PERMEABILITY; INDUCIBLE EXPRESSION; CONE PHOTORECEPTORS;
   PIGMENT EPITHELIUM
AB Vascular endothelial growth factor (VEGF-A) is a major pathogenic factor and a therapeutic target for age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. Despite intensive effort in the field, the cellular mechanisms of VEGF action remain virtually uninvestigated. This situation makes it difficult to design cellular target-based therapeutics for these diseases. In light of the recent finding that VEGF is a potential neurotrophic factor, revealing the cellular mechanisms of VEGF action becomes necessary to preserve its beneficial effect and inhibit its pathological function in long-term anti-VEGF therapeutics for ocular vascular diseases. We therefore generated conditional VEGF knockout mice with an inducible Cre/lox system and determined the significance of Muller cell-derived VEGF in retinal development and maintenance and ischaemia-induced neovascularizartion and vascular leakage. Retinal development in the conditional VEGF knockout mice was analysed by examining retinal and choroidal vasculatures and retinal morphology and function. Ischaemia-induced retinal neovascularization and vascular leakage in the conditional VEGF knockout mice were analysed with fluorescein angiography, quantification of proliferative neovascular cells, immunohistochemistry, and immunoblotting using an oxygen-induced retinopathy model. Our results demonstrated that disruption of Muller cell-derived VEGF resulted in no apparent defects in retinal and choroidal vasculatures and retinal morphology and function, significant inhibition of the ischaemia-induced retinal neovascularization and vascular leakage, and attenuation of the ischaemia-induced breakdown of the blood-retina barrier. These results suggest that the retinal Muller cell-derived VEGF is a major contributor to ischaemia-induced retinal vascular leakage and pre-retinal and intra-retinal neovascularization. The observation that a significant, but not complete, reduction of VEGF in the retina does not cause detectable retinal degeneration suggests that appropriate doses of anti-VEGF agents may be important to the safe treatment of retinal vascular diseases. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 [Bai, Yanyan; Ma, Jian-xing; Guo, Junjing; Wang, Juanjuan; Zhu, Meili; Chen, Ying; Le, Yun-Zheng] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA.
   [Bai, Yanyan; Ma, Jian-xing; Guo, Junjing; Wang, Juanjuan; Zhu, Meili; Chen, Ying; Le, Yun-Zheng] Univ Oklahoma, Hlth Sci Ctr, Harold Hamm Oklahoma Diabet Ctr, Oklahoma City, OK 73104 USA.
   [Bai, Yanyan] Soochow Univ, Dept Med, Suzhou 215123, Peoples R China.
   [Ma, Jian-xing; Le, Yun-Zheng] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA.
   [Guo, Junjing] Harbin Med Coll, Affiliated Hosp 2, Dept Ophthalmol, Harbin 150086, Peoples R China.
   [Wang, Juanjuan] Cent S Univ, Xiangya Hosp, Dept Ophthalmol, Changsha 410008, Hunan, Peoples R China.
   [Le, Yun-Zheng] Dean McGee Eye Inst, Oklahoma City, OK 73104 USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; University of Oklahoma System; University of Oklahoma Health
   Sciences Center; Soochow University - China; University of Oklahoma
   System; University of Oklahoma Health Sciences Center; Harbin Medical
   University; Central South University
RP Le, YZ (通讯作者)，941 SL Young Blvd,BSEB 302G, Oklahoma City, OK 73104 USA.
EM Yun-Le@ouhsc.edu
RI wang, juanjuan/GYV-5540-2022
OI Bai, Yanyan/0000-0002-8365-8451
FU NIH [P20 RR17703, P20 RR024215, P30 EY12190, EY015650, EY012231]; ADA
   [1-06-RA-76]; JDRF [5-2005-1292]; AHAF [M2008-059]; FFB
   [BR-CMM-0808-0453-UOK]; OCAST [HR09-058]; Hope for Vision and Research
   to Prevent Blindness, Inc.; NATIONAL CENTER FOR RESEARCH RESOURCES
   [P20RR024215, P20RR017703] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [R21EY015650, R33EY015650, P30EY012190, R01EY012231] Funding
   Source: NIH RePORTER
FX We thank W Zheng and G Zeng for technical assistance, Dr N Ferrara and
   Genentech Inc for providing floxed VEGF mice, and J Ash and M Elliott
   for helpful suggestions. This study was supported by NIH grants P20
   RR17703, P20 RR024215, P30 EY12190, EY015650, and EY012231; ADA grant
   1-06-RA-76; JDRF grant 5-2005-1292; AHAF grant M2008-059; FFB grant
   BR-CMM-0808-0453-UOK; OCAST grant HR09-058; and unrestricted research
   awards from Hope for Vision and Research to Prevent Blindness, Inc.
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NR 43
TC 166
Z9 179
U1 0
U2 14
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3417
EI 1096-9896
J9 J PATHOL
JI J. Pathol.
PD DEC
PY 2009
VL 219
IS 4
BP 446
EP 454
DI 10.1002/path.2611
PG 9
WC Oncology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Pathology
GA 532BZ
UT WOS:000272720200008
PM 19768732
DA 2022-11-30
ER

PT J
AU Wei, Y
   Wang, X
   Wang, L
AF Wei, Yan
   Wang, Xu
   Wang, Ling
TI Presence and regulation of cannabinoid receptors in human retinal
   pigment epithelial cells
SO MOLECULAR VISION
LA English
DT Article
ID MITOCHONDRIAL-DNA DAMAGE; MACULAR DEGENERATION; ENDOCANNABINOID SYSTEM;
   MULTIPLE-SCLEROSIS; ENDOGENOUS CANNABINOIDS; INDUCED NEUROTOXICITY;
   PARKINSONS-DISEASE; OXIDATIVE STRESS; GOLDFISH RETINA; BIPOLAR CELLS
AB Purpose: Cannabinoid receptors have been detected in neuron cells and proposed as potential therapeutic agents in neurodegenerative disorders because of their involvement in controlling neural cell survival and death. However, their presence and role in human retinal pigment epithelial (RPE) cells, which play a key role in initiating and developing age related macular degeneration (ARMD), have never been investigated. Here we analyzed the expression of and changes in cannabinoid receptors (CB1 and CB2) and one enzyme responsible for endocannabinoid hydrolysis, fatty acid amide hydrolase (FAAH), in RPE cell oxidative damage process, a cellular model of ARMD.
   Methods: Primary human RPE cells and cells from the ARPE-19 cell line were cultured and exposed to H2O2 for 24 h to induce oxidative damage. Real time RT-PCR, immunofluorescent staining, and western blot methods were performed to study the expression of and changes in CB1 and CB2 receptors, and FAAH. Cell viability and reactive oxygen species (ROS) production were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and a dichlorofluorescein (DCF) assay, respectively. PI3K/Akt and ERK1/2 protein expression and activation of signaling molecules were assessed by western blot analysis.
   Results: By using real time RT-PCR, immunofluorescent staining and western blot methods, we showed that human RPE cells express CB1, CB2, and FAAH. Meanwhile, oxidative stress can upregulate CB1 and CB2 receptor expression, and downregulate FAAH expression. The CB1/CB2 receptor agonist, CP55,940, and the CB2 receptor agonist, JWH015 significantly protected RPE cells from oxidative damage. In addition, CP55,940 significantly reduced the levels of intracellular ROS, strengthened oxidative stress-induced activation of PI3K/Akt and reduced activation of the ERK1/2 signal pathway.
   Conclusions: The results demonstrate the expression and regulation of CB1 and CB2 receptors and FAAH in human RPE cells. The modulation of cannabinoid receptor tone warrants consideration for future therapeutic strategies of ARMD.
C1 [Wei, Yan; Wang, Ling] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Ophthalmol, Shanghai 200025, Peoples R China.
   [Wang, Xu] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 200031, Peoples R China.
C3 Shanghai Jiao Tong University; Chinese Academy of Sciences; Shanghai
   Institute of Materia Medica, CAS
RP Wang, L (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Ophthalmol, Shanghai 200025, Peoples R China.
EM l.wang_rjeye@163.com
FU Shanghai Leading Academic Discipline [S30205]; Shanghai Science and
   Technology Committee [08JC1415600]
FX We greatly appreciate the support received from Shanghai Leading
   Academic Discipline Project S30205 and Shanghai Science and Technology
   Committee 08JC1415600.
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NR 47
TC 45
Z9 47
U1 0
U2 2
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUN 14
PY 2009
VL 15
IS 132-33
BP 1243
EP 1251
PG 9
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 470OY
UT WOS:000267986500001
PM 19547718
DA 2022-11-30
ER

PT J
AU Gunnlaugsdottir, E
   Arnarsson, A
   Jonasson, F
AF Gunnlaugsdottir, Elin
   Arnarsson, Arsaell
   Jonasson, Fridbert
TI Prevalence and causes of visual impairment and blindness in Icelanders
   aged 50 years and older: the Reykjavik Eye Study
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE blindness; geographic atrophy; prevalence; visual impairment
ID POPULATION; ACUITY; MACULOPATHY; GLAUCOMA; AUSTRALIA; AMBLYOPIA
AB Purpose: This study aimed to study the prevalences and causes of visual impairment and blindness in an Icelandic adult population.
   Methods: The Reykjavik Eye Study includes a random sample of citizens of Reykjavik aged >= 50 years, with an equal proportion (6.4%) for each year of birth and each sex. A total of 1045 persons were examined, representing a response rate of 75.8%. All participants underwent an extensive ophthalmological examination using a standard protocol. We used World Health Organization (WHO) definitions for bilateral visual impairment (best corrected visual acuity [VA] < 6/18 or visual field of >= 5 degrees and < 10 degrees around the fixation point in the better eye) and blindness (VA < 3/60 or visual field < 5 degrees in the better eye). We also used US criteria, which define bilateral visual impairment as present if VA is < 6/12 and blindness as present if VA is <= 6/60 (both in the better eye). The causes of visual loss were determined for all participants found to be visually impaired in one or both eyes.
   Results: The prevalences of bilateral visual impairment and blindness were 0.96% (95% confidence interval [CI] 0.37-1.55) and 0.57% (95% CI 0.12-1.03), respectively, using the WHO criteria, and 2.01% (95% CI 1.16-2.86) and 0.77% (95% CI 0.24-1.29), respectively, using the US criteria. The prevalence rates were 4.40% and 5.45% for unilateral visual impairment and 1.72% and 3.06% for unilateral blindness, using the WHO and US criteria, respectively. Age-related macular degeneration (AMD) was the major cause of bilateral visual loss, whereas the most common causes of unilateral visual loss were, in this order, amblyopia, cataract and glaucoma.
   Conclusions: Prevalence of visual loss increases with age. The leading cause of bilateral visual impairment and blindness was AMD, accounting for more than half of all cases, and cases of geographic atrophy outnumbered those of exudative AMD by two to one.
C1 [Gunnlaugsdottir, Elin; Arnarsson, Arsaell; Jonasson, Fridbert] Univ Iceland, Dept Ophthalmol, Reykjavik, Iceland.
   [Arnarsson, Arsaell] Univ Akureyri, Dept Social Sci, Akureyri, Iceland.
C3 University of Iceland; University of Akureyri
RP Jonasson, F (通讯作者)，Univ Eye Dept, Landspitalinn, IS-101 Reykjavik, Iceland.
EM fridbert@landspitali.is
RI Jonasson, Fridbert/ABA-9889-2021
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NR 31
TC 54
Z9 56
U1 0
U2 11
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD NOV
PY 2008
VL 86
IS 7
BP 778
EP 785
DI 10.1111/j.1755-3768.2008.01191.x
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 367BJ
UT WOS:000260527200014
PM 18513265
OA Bronze
DA 2022-11-30
ER

PT J
AU Fink, W
   Sadun, AA
AF Fink, W
   Sadun, AA
TI Three-dimensional computer-automated threshold Amsler grid test
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE Amsler grid test; scotomas
ID PARACENTRAL SCOTOMAS
AB We describe a novel method for testing a visual field that employs a computer monitor with displays of varying contrast that permits unprecedented resolution and characterization of the structure of scotomas in three dimensions. Patients are placed in front of a touch-sensitive computer screen at a fixed distance. With one eye covered, they focus on a central fixation marker and trace with their finger the areas on an Amsler grid that are missing from their field of vision. Increasing degrees of contrast of the Amsler grid are simulated by repeating the test at different gray-scale levels. The results are recorded and then displayed as topographical contour rings by the computer test program. The results can also be rendered as an immediate 3-D depiction of the central hill-of-vision. Several clinical pilot studies have been conducted at the Doheny Eye Institute and more than 200 patients have been examined with this system so far. Conditions such as optic neuritis, anterior ischemic optic neuropathy (AION), age-related macular degeneration (AMD), glaucoma, and ocular hypertension have been successfully assessed by this test. Each condition provides unique patterns that are most evident in 3-D. The 3-D computer-automated threshold Amsler grid test is an innovative and noninvasive visual field test. It provides several advantages over state-of-the-art standard automated perimetry, including: (1) additional information through 3-D depiction of scotomas, such as location, extent, slope, depth, and shape; (2) high angular resolution (1 deg compared with typically 6 deg); (3) a simple test setup (merely a touch-sensitive computer monitor and the test software); (4) excellent patient compliance (spending 4 to 5 min per eye). In light of its promising initial tests, the 3-D visual field test appears to have the potential for the early detection and monitoring of various diseases over time. 2004 Society of Photo-Optical Instrumentation Engineers.
C1 CALTECH, Pasadena, CA 91125 USA.
   Univ So Calif, Doheny Eye Inst, Keck Sch Med, Los Angeles, CA USA.
C3 California Institute of Technology; Doheny Eye Institute; University of
   Southern California
RP Fink, W (通讯作者)，CALTECH, Pasadena, CA 91125 USA.
EM wfin@krl.caltech.edu
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NR 20
TC 26
Z9 32
U1 0
U2 7
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
EI 1560-2281
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD JAN-FEB
PY 2004
VL 9
IS 1
BP 149
EP 153
DI 10.1117/1.1625952
PG 5
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
GA 765BR
UT WOS:000188247700015
PM 14715067
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Borodoker, N
   Spaide, RF
   Maranan, L
   Murray, J
   Freund, KB
   Slakter, JS
   Sorenson, JA
   Yannuzzi, LA
   Guyer, DR
   Fisher, YL
AF Borodoker, N
   Spaide, RF
   Maranan, L
   Murray, J
   Freund, KB
   Slakter, JS
   Sorenson, JA
   Yannuzzi, LA
   Guyer, DR
   Fisher, YL
TI Verteporfin infusion-associated pain
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID CHOROIDAL NEOVASCULARIZATION; PHOTODYNAMIC THERAPY; MACULAR
   DEGENERATION; BENZOPORPHYRIN; PHASE-1; CHEST
AB PURPOSE: To determine if oral hydration decreases the incidence of verteporfin infusion-associated pain and to find out if other factors play a role in predisposing to this undesired complication.
   METHODS: Nonrandomized clinical trial. We prospectively examined 250 consecutive patients who have been diagnosed with subfoveal choroidal neovascularization secondary to age-related macular degeneration and received photodynamic therapy using verteporfin. One hundred twenty-five patients were assigned to receive 500 ml of water orally administered 30 minutes before beginning the verteporfin infusion, and the remaining 125 consecutive patients were used as controls. Historical and clinical factors in these patients were evaluated for their association with the presence of verteporfin infusion-associated pain.
   RESULTS: Out of 125 patients receiving water before treatment 12 (9.6%) experienced verteporfin infusion-associated pain. Among the 125 patients who did not get hydration before therapy 12 (9.6%) experienced verteporfin infusion-associated pain. There was no statistical difference between the incidence of pain in the two groups (P = 1.0). No statistically significant association was evidenced between the presence of pain and participant's baseline characteristics, except for pain on previous administration of verteporfin (P < .001). Out of 250 total patients 24 (9.6%) developed verteporfin infusions associated pain. Back pain was the most common and occurred in 21 (8.4%) patients, but other sites included leg, groin, chest, buttock, arm, and shoulder pain cone currently or independently. All patients had resolution of their pain, including chest pain, on cessation of the infusion.
   CONCLUSIONS: Verteporfin infusion,associated pain may be more common than has been previously reported and is not limited to the back area. It appears to be an idiosyncratic reaction to the drug. It does not seem to be prevented by oral hydration before infusion of verteporfin, and no baseline characteristics, other than a history of pain on previous infusion, seem to be predictive of verteporfin infusion-associated pain. (Am J Ophthalmol 2002;133:211-214. (C) 2002 by Elsevier Science Inc. All rights reserved.).
C1 Vitreous Retina Macula Consultants New York, New York, NY 10021 USA.
   Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA.
C3 Vitreous Retina Macula Consultants of New York; Manhattan Eye Ear &
   Throat Hospital
RP Spaide, RF (通讯作者)，Vitreous Retina Macula Consultants New York, 519 E 72nd St,Suite 203, New York, NY 10021 USA.
RI Spaide, Richard/ABD-7368-2020; Freund, K. Bailey/V-7488-2018
OI Freund, K. Bailey/0000-0002-7888-9773
CR ALLISON BA, 1994, BRIT J CANCER, V69, P833, DOI 10.1038/bjc.1994.162
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NR 10
TC 13
Z9 14
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD FEB
PY 2002
VL 133
IS 2
BP 211
EP 214
DI 10.1016/S0002-9394(01)01341-1
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 518LM
UT WOS:000173669900005
PM 11812424
DA 2022-11-30
ER

PT J
AU Frazer-Abel, A
   Kirschfink, M
   Prohaszka, Z
AF Frazer-Abel, Ashley
   Kirschfink, Michael
   Prohaszka, Zoltan
TI Expanding Horizons in Complement Analysis and Quality Control
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE complement; laboratory analysis; quality control; diagnostic test; assay
   performance
ID FACTOR-H; SYSTEM; ACTIVATION; ECULIZUMAB; DEFICIENCIES; DISEASES;
   PATHWAY; IMMUNODEFICIENCIES; AUTOANTIBODIES; CONSEQUENCES
AB Complement not only plays a key role in host microbial defense but also modulates the adaptive immune response through modification of T- and B-cell reactivity. Moreover, a normally functioning complement system participates in hematopoiesis, reproduction, lipid metabolism, and tissue regeneration. Because of its powerful inflammatory potential, multiple regulatory proteins are needed to prevent potential tissue damage. In clinical practice, dysregulation and overactivation of the complement system are major causes of a variety of inflammatory and autoimmune diseases ranging from nephropathies, age-related macular degeneration (AMD), and systemic lupus erythematosus (SLE) to graft rejection, sepsis, and multi-organ failure. The clinical importance is reflected by the recent development of multiple drugs targeting complement with a broad spectrum of indications. The recognition of the role of complement in diverse diseases and the advent of complement therapeutics has increased the number of laboratories and suppliers entering the field. This has highlighted the need for reliable complement testing. The relatively rapid expansion in complement testing has presented challenges for a previously niche field. This is exemplified by the issue of cross-reactivity of complement-directed antibodies and by the challenges of the poor stability of many of the complement analytes. The complex nature of complement testing and increasing clinical demand has been met in the last decade by efforts to improve the standardization among laboratories. Initiated by the IUIS/ICS Committee for the Standardization and Quality Assessment in Complement Measurements 14 rounds of external quality assessment since 2010 resulted in improvements in the consistency of testing across participating institutions, while extending the global reach of the efforts to more than 200 laboratories in 30 countries. Worldwide trends of assay availability, usage, and analytical performance are summarized based on the past years' experiences. Progress in complement analysis has been facilitated by the quality assessment and standardization efforts that now allow complement testing to provide a comprehensive insight into deficiencies and the activation state of the system. This in turn enables clinicians to better define disease severity, evolution, and response to therapy.
C1 [Frazer-Abel, Ashley] Univ Colorado, Exsera Biolabs, Aurora, CO USA.
   [Kirschfink, Michael] Heidelberg Univ, Inst Immunol, Heidelberg, Germany.
   [Prohaszka, Zoltan] Res Lab Semmelweis Univ, Dept Med & Hematol, Budapest, Hungary.
C3 University of Colorado System; University of Colorado Anschutz Medical
   Campus; Ruprecht Karls University Heidelberg
RP Prohaszka, Z (通讯作者)，Res Lab Semmelweis Univ, Dept Med & Hematol, Budapest, Hungary.
EM prohaszka.zoltan@med.semmelweis-univ.hu
FU National Office for Innovation and Research "Befektetes a jovo.be"
   [2020-1-1-6-JOVO-202100013]
FX The research was financed by the National Office for Innovation and
   Research "Befektetes a jovo.be" (2020-1-1-6-JOVO-202100013) to ZP.
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NR 94
TC 8
Z9 8
U1 2
U2 13
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD AUG 9
PY 2021
VL 12
AR 697313
DI 10.3389/fimmu.2021.697313
PG 12
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA UF1DY
UT WOS:000688323000001
PM 34434189
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Allen, P
   Calcagni, A
   Robson, AG
   Claridge, E
AF Allen, Piers
   Calcagni, Antonio
   Robson, Anthony G.
   Claridge, Ela
TI Investigating the potential of Zernike polynomials to characterise
   spatial distribution of macular pigment
SO PLOS ONE
LA English
DT Article
ID OPTICAL-DENSITY MEASUREMENT; FUNDUS AUTOFLUORESCENCE;
   QUANTITATIVE-ANALYSIS; EYE DISEASE; AGE; DEGENERATION; CAROTENOIDS;
   ZEAXANTHIN; LUTEIN; REFLECTANCE
AB It has been postulated that particular patterns of macular pigment (MP) distribution may be associated with the risk for eye diseases such as age-related macular degeneration (AMD). This work investigates the potential of Zernike polynomials (ZP) to characterise the level and distribution of MP, and their suitability as a representation for analysis of the effects of age and AMD on MP patterns. As the case study, MP distribution maps computed using an experimental method based on fundus reflectance (MRIA) were obtained for ninety volunteers representing three groups: under-fifty without AMD, fifty and over without AMD, and fifty and over with AMD. ZP with 105 coefficients were fitted to the maps using least-squares optimisation and found to represent MP maps accurately (RMSE<10-1). One-way MANOVA analysis carried out on ZP representations showed that the three subject groups have significantly different means (Wilk's Lambda 0.125, p<0.0001). Linear discriminant analysis with leave-one-out scheme resulted in accuracy, sensitivity and specificity of classification according to, respectively, disease status regardless of age (81% all); disease status in the age-matched groups (87%, 88%, 86%); age irrespective of disease status (81%, 83%, 73%); and age for subjects without AMD (83%, 88%, 80%). Mean MP distributions computed from ZP coefficients for the three groups showed more elevated and more peaked MP for the healthy under-fifty group; more irregular and more elevated peripheral levels in over-fifty AMD group than in over-fifty non-AMD group; and moderate radial asymmetry in non-AMD over-50 group. The results suggest that ZP coefficients are capable of accurately representing MP in a way that captures certain spatial patterns of its distribution. Using the ZP representation MP maps could be classified according to both age and disease status with accuracy significantly greater than chance, with peak elevation, pattern irregularity and radial asymmetry identified as important features.
C1 [Allen, Piers; Calcagni, Antonio; Claridge, Ela] Univ Birmingham, Sch Comp Sci, Birmingham, W Midlands, England.
   [Calcagni, Antonio] Aston Univ, Ophthalm Res Grp, Sch Life & Hlth Sci, Birmingham, W Midlands, England.
   [Calcagni, Antonio; Robson, Anthony G.] Moorfields Eye Hosp NHS Fdn Trust, Dept Electrophysiol, London, England.
   [Robson, Anthony G.] UCL, Inst Ophthalmol, London, England.
   [Allen, Piers] Univ Birmingham, Res & Training Ctr Phys Sci Hlth, Birmingham, W Midlands, England.
C3 University of Birmingham; Aston University; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   University of London; University College London; University of
   Birmingham
RP Claridge, E (通讯作者)，Univ Birmingham, Sch Comp Sci, Birmingham, W Midlands, England.
EM e.claridge@cs.bham.ac.uk
OI Calcagni, Antonio Salvatore Pio/0000-0002-1446-3546; Robson,
   Anthony/0000-0002-8391-6123
FU Dunhill Medical Trust [R116/0509]; Paul & Yuanbi Ramsay Research Fund,
   University of Birmingham; NIHR Biomedical Research Centre at Moorfields
   Eye Hospital NHS Foundation Trust; UCL Institute of Ophthalmology
FX This work was supported by the Dunhill Medical Trust, grant number
   R116/0509, (http://dunhillmedical.org.uk) to EC, AC; Paul & Yuanbi
   Ramsay Research Fund, University of Birmingham to PA. AGR wishes to
   acknowledge support by the NIHR Biomedical Research Centre at Moorfields
   Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.
   The funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.; The authors wish
   to acknowledge contributions that the following colleagues made to the
   development of the Multispectral Retinal Image Analysis technique and to
   image data collection: Professor Jonathan M Gibson, Dr Frank Eperjesi,
   Dr Hannah Bartlett ( Aston University, Birmingham, U.K.), Dr Iain B
   Styles and Dr Yuan Shen ( University of Birmingham, U.K.). Anthony G
   Robson wishes to acknowledge support by the NIHR Biomedical Research
   Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute
   of Ophthalmology.
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TC 2
Z9 2
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 24
PY 2019
VL 14
IS 5
AR e0217265
DI 10.1371/journal.pone.0217265
PG 19
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HZ5BN
UT WOS:000468865700026
PM 31125363
OA Green Published, gold, Green Submitted, Green Accepted
DA 2022-11-30
ER

PT J
AU Balyen, L
   Peto, T
AF Balyen, Lokman
   Peto, Tunde
TI Promising Artificial Intelligence-Machine Learning-Deep Learning
   Algorithms in Ophthalmology
SO ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE age-related macular degeneration; deep learning; diabetic retinopathy;
   glaucoma; machine learning
ID DIABETIC-RETINOPATHY; AUTOMATED IDENTIFICATION; KERATOCONUS DETECTION;
   RETINAL-DETACHMENT; NEURAL-NETWORKS; RISK-FACTORS; IMAGES; SEGMENTATION;
   CATARACT; PREMATURITY
AB The lifestyle of modern society has changed significantly with the emergence of artificial intelligence (AI), machine learning (ML), and deep learning (DL) technologies in recent years. Artificial intelligence is a multidimensional technology with various components such as advanced algorithms, ML and DL. Together, AI, ML, and DL are expected to provide automated devices to ophthalmologists for early diagnosis and timely treatment of ocular disorders in the near future. In fact, AI, ML, and DL have been used in ophthalmic setting to validate the diagnosis of diseases, read images, perform corneal topographic mapping and intraocular lens calculations. Diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma are the 3 most common causes of irreversible blindness on a global scale. Ophthalmic imaging provides a way to diagnose and objectively detect the progression of a number of pathologies including DR, AMD, glaucoma, and other ophthalmic disorders. There are 2 methods of imaging used as diagnostic methods in ophthalmic practice: fundus digital photography and optical coherence tomography (OCT). Of note, OCT has become the most widely used imaging modality in ophthalmology settings in the developed world. Changes in population demographics and lifestyle, extension of average lifespan, and the changing pattern of chronic diseases such as obesity, diabetes, DR, AMD, and glaucoma create a rising demand for such images. Furthermore, the limitation of availability of retina specialists and trained human graders is a major problem in many countries. Consequently, given the current population growth trends, it is inevitable that analyzing such images is time-consuming, costly, and prone to human error. Therefore, the detection and treatment of DR, AMD, glaucoma, and other ophthalmic disorders through unmanned automated applications system in the near future will be inevitable. We provide an overview of the potential impact of the current AI, ML, and DL methods and their applications on the early detection and treatment of DR, AMD, glaucoma, and other ophthalmic diseases.
C1 [Balyen, Lokman] Kafkas Univ, Fac Med, Dept Ophthalmol, Kars, Turkey.
   [Peto, Tunde] Queens Univ Belfast, Sch Med, Inst Clin Sci, Dept Ophthalmol,Ctr Publ Hlth, Belfast, Antrim, North Ireland.
C3 Kafkas University; Queens University Belfast
RP Balyen, L (通讯作者)，Kafkas Univ, Fac Med, Dept Ophthalmol, Kars, Turkey.
EM lbalyen@hotmail.com
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NR 86
TC 65
Z9 66
U1 11
U2 51
PU ASIA-PACIFIC ACAD OPHTHALMOLOGY-APAO
PI KOWLOON
PA 4-F, HONG KONG EYE HOSP, 147K ARGYLE ST, KOWLOON, KOWLOON, HONG KONG
   00000, PEOPLES R CHINA
EI 2162-0989
J9 ASIA-PAC J OPHTHALMO
JI Asia-Pac. J. Ophthalmol.
PD MAY-JUN
PY 2019
VL 8
IS 3
BP 264
EP 272
DI 10.22608/APO.2018479
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JT1TD
UT WOS:000500779400013
PM 31149787
OA Green Accepted, gold
DA 2022-11-30
ER

PT J
AU McCarthy, G
   Fenu, E
   Bennett, N
   Almond, C
AF McCarthy, Grant
   Fenu, Elisabetta
   Bennett, Natalie
   Almond, Chrissy
TI Intravitreal Ranibizumab for the Treatment of Visual Impairment Due to
   Choroidal Neovascularization Associated with Rare Diseases:
   Cost-Effectiveness in the UK
SO ADVANCES IN THERAPY
LA English
DT Article
DE Choroidal neovascularization; Cost-effectiveness; Economic evaluation;
   Ophthalmology; Ranibizumab; VEGF
ID MACULAR DEGENERATION; AFLIBERCEPT INJECTION; VISION LOSS; SIMULATION;
   SECONDARY; BLINDNESS; YOUNG
AB Introduction: This study sought to determine the cost-effectiveness of intravitreal ranibizumab compared with best supportive care (BSC; considered to be no active treatment) for the treatment of visual impairment due to choroidal neovascularization (CNV) associated with causes other than neovascular age-related macular degeneration (nAMD) and pathologic myopia (PM) in a UK setting.
   Methods: An individual patient-level simulation model was developed to estimate the lifetime costs and quality-adjusted life years (QALYs) of ranibizumab vs. BSC. Regression analyses, performed on patient-level data collected within the pivotal phase III MINERVA trial, modelled visual acuity (VA) progression while patients remained on treatment. Patient utilities were modelled as a function of VA in both eyes and resource use estimates were based on trial data or the literature. Costs were evaluated from the perspective of the UK National Health Service and personal social services, with future costs and health outcomes discounted at 3.5% per annum. Sensitivity and scenario analyses were conducted.
   Results: The incremental cost-effectiveness ratio for intravitreal ranibizumab was 1363 per QALY compared to BSC and was associated with an incremental benefit of 1.06 QALYs and an incremental cost of 1444 per patient. Drug and administration costs of intravitreal ranibizumab were offset by the prevention of the development of blindness and its associated costs, while the increase in benefits was driven by a reduction in mortality risk and an improved health-related quality of life attributed to an improvement in VA. The findings were robust to a range of sensitivity analyses and ranibizumab consistently remained cost-effective at a willingness-to-pay threshold of 20,000-30,000 pound per QALY gained for all sensitivity analyses.
   Conclusion: Intravitreal ranibizumab is a highly cost-effective intervention for the treatment of CNV due to causes other than nAMD and PM as it delivers substantial QALY gains to patients while making cost savings vs. BSC.
C1 [McCarthy, Grant; Fenu, Elisabetta; Almond, Chrissy] BresMed Hlth Solut Ltd, Sheffield, S Yorkshire, England.
   [Bennett, Natalie] Novartis Pharmaceut UK Ltd, Camberley, Surrey, England.
C3 Novartis
RP Bennett, N (通讯作者)，Novartis Pharmaceut UK Ltd, Camberley, Surrey, England.
EM natalie.bennett@novartis.com
RI McCarthy, Grant/AAA-5445-2021
OI McCarthy, Grant/0000-0001-8292-8598
FU Novartis Pharmaceuticals UK Ltd, Surrey, UK; Novartis Pharmaceuticals UK
   Ltd.
FX This study was funded by Novartis Pharmaceuticals UK Ltd, Surrey, UK.
   Funding for the article processing charges was provided by Novartis
   Pharmaceuticals UK Ltd. All authors had full access to all of the data
   in this study and take complete responsibility for the integrity of the
   data and accuracy of the data analysis.
CR Bennett N, 2018, ADV THER, V35, P591, DOI 10.1007/s12325-018-0698-9
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NR 34
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0741-238X
EI 1865-8652
J9 ADV THER
JI Adv. Ther.
PD MAR
PY 2019
VL 36
IS 3
BP 632
EP 644
DI 10.1007/s12325-019-0894-2
PG 13
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA HQ1AT
UT WOS:000462129500009
PM 30726549
DA 2022-11-30
ER

PT J
AU Grassmann, F
   Bergholz, R
   Mandl, J
   Jagle, H
   Ruether, K
   Weber, BHF
AF Grassmann, Felix
   Bergholz, Richard
   Maendl, Julia
   Jaegle, Herbert
   Ruether, Klaus
   Weber, Bernhard H. F.
TI Common synonymous variants in ABCA4 are protective for chloroquine
   induced maculopathy (toxic maculopathy)
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Chloroquine induced maculopathy; ABCA4; Age-related macular
   degeneration; Stargardt's disease; Genetic association
ID RETINAL TOXICITY; HYDROXYCHLOROQUINE RETINOPATHY; MACULAR DEGENERATION;
   STARGARDT-DISEASE; GENE ABCR; MUTATIONS; RPE; ACCUMULATION; CELLS; RISK
AB Background: Chloroquine (CQ) and hydroxychloroquine (HCQ) are used to treat auto-immune related diseases such as rheumatoid arthritis (RA) or systemic lupus erythematosus. Both drugs however can cause retinal toxicity eventually leading to irreversible maculopathy and retinopathy. Established risk factors are duration and dosage of treatment while the involvement of genetic factors contributing to toxic maculopathy is largely unclear. To address the latter issue, this study aimed to expand on earlier efforts by (1) evaluating risk-altering variants known to be associated with age-related macular degeneration (AMD), a frequent maculopathy in individuals over 55 years of age, and (2) determining the contribution of genetic variants in the coding sequence of the ABCA4 gene.
   Methods: The ABCA4 gene was analyzed by deep sequencing technology using a personal genome machine (Ion Torrent) with 200 bp read length. Assessment of AMD variants was done by restriction enzyme digestion of PCR products and TaqMan SNP genotyping. Effect sizes, p-values and confidence intervals of common variants were evaluated by logistic regression (Firth's bias corrected). To account for multiple testing, p-values were adjusted according to the false discovery rate.
   Results: We found no effects of known AMD-associated variants on the risk of toxic maculopathy. In contrast, we report a statistically significant association of common variants in the ABCA4 gene with retinal disease, assessed by a score-based variance-component test (P-SKAT = 0.0055). This association remained significant after adjustment for environmental factors like age and duration of medication and was driven by three common variants in ABCA4 (c.5682G > C, c.5814A > G, c.5844A > G), all conferring a reduced risk for toxic maculopathy.
   Conclusions: Our findings demonstrate that minor alleles of common genetic variants in ABCA4 significantly reduce susceptibility to develop toxic maculopathy under CQ treatment. A refined risk profile based on genetic and environmental factors may have implications for revised recommendations in CQ as well as HCQ treatment.
C1 [Grassmann, Felix; Maendl, Julia; Weber, Bernhard H. F.] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
   [Bergholz, Richard] Charite Augenklin Campus Virchow Klinikum, D-13353 Berlin, Germany.
   [Jaegle, Herbert] Univ Hosp Regensburg, Dept Ophthalmol, D-93053 Regensburg, Germany.
   [Ruether, Klaus] Sankt Gertrauden Krankenhaus, Augenklin, D-10713 Berlin, Germany.
C3 University of Regensburg; Free University of Berlin; Humboldt University
   of Berlin; Charite Universitatsmedizin Berlin; University of Regensburg;
   University of Hamburg; University Medical Center Hamburg-Eppendorf
RP Weber, BHF (通讯作者)，Univ Regensburg, Inst Human Genet, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany.
EM bweb@klinik.uni-regensburg.de
RI Jägle, Herbert/GPP-2945-2022
OI Weber, Bernhard H.F./0000-0002-8808-7723; Bergholz,
   Richard/0000-0001-7352-7653; Grassmann, Felix/0000-0003-1390-7528
FU Institute of Human Genetics, Regensburg; Charite Eye Clinic, Berlin
FX We are grateful to the patients and control subjects for their
   participation in this study. We also want to thank Kerstin Meier and
   Yvonne Bilek for her excellent technical support. This work was
   supported in part by institutional funds (Institute of Human Genetics,
   Regensburg, and Charite Eye Clinic, Berlin). Design, collection,
   analysis or interpretation of data was not influenced by the respective
   funding bodies.
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NR 29
TC 26
Z9 27
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD MAR 6
PY 2015
VL 15
AR 18
DI 10.1186/s12886-015-0008-0
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CC8CL
UT WOS:000350595600001
PM 25884411
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Song, W
   Wei, Q
   Jiao, SL
   Zhang, HF
AF Song, Wei
   Wei, Qing
   Jiao, Shuliang
   Zhang, Hao F.
TI Integrated Photoacoustic Ophthalmoscopy and Spectral-domain Optical
   Coherence Tomography
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Biomedical Engineering; Issue 71; Bioengineering; Medicine; Anatomy;
   Physiology; Opthalmology; Physics; Biophysics; Photoacoustic;
   ophthalmology; ophthalmoscopy; optical coherence tomography; retinal
   imaging; spectral-domain; tomography; rat; animal model; imaging
AB Both the clinical diagnosis and fundamental investigation of major ocular diseases greatly benefit from various non-invasive ophthalmic imaging technologies. Existing retinal imaging modalities, such as fundus photography(1), confocal scanning laser ophthalmoscopy (cSLO)(2), and optical coherence tomography (OCT)(3), have significant contributions in monitoring disease onsets and progressions, and developing new therapeutic strategies. However, they predominantly rely on the back-reflected photons from the retina. As a consequence, the optical absorption properties of the retina, which are usually strongly associated with retinal pathophysiology status, are inaccessible by the traditional imaging technologies.
   Photoacoustic ophthalmoscopy (PAOM) is an emerging retinal imaging modality that permits the detection of the optical absorption contrasts in the eye with a high sensitivity(4-7). In PAOM nanosecond laser pulses are delivered through the pupil and scanned across the posterior eye to induce photoacoustic (PA) signals, which are detected by an unfocused ultrasonic transducer attached to the eyelid. Because of the strong optical absorption of hemoglobin and melanin, PAOM is capable of non-invasively imaging the retinal and choroidal vasculatures, and the retinal pigment epithelium (RPE) melanin at high contrasts(6,7). More importantly, based on the well-developed spectroscopic photoacoustic imaging(5,8), PAOM has the potential to map the hemoglobin oxygen saturation in retinal vessels, which can be critical in studying the physiology and pathology of several blinding diseases(9) such as diabetic retinopathy and neovascular age-related macular degeneration.
   Moreover, being the only existing optical-absorption-based ophthalmic imaging modality, PAOM can be integrated with well-established clinical ophthalmic imaging techniques to achieve more comprehensive anatomic and functional evaluations of the eye based on multiple optical contrasts(6,10). In this work, we integrate PAOM and spectral-domain OCT (SD-OCT) for simultaneously in vivo retinal imaging of rat, where both optical absorption and scattering properties of the retina are revealed. The system configuration, system alignment and imaging acquisition are presented.
C1 [Song, Wei; Wei, Qing; Zhang, Hao F.] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA.
   [Song, Wei] Harbin Inst Technol, Dept Phys, Harbin, Peoples R China.
   [Jiao, Shuliang] Univ So Calif, Dept Ophthalmol, Los Angeles, CA 90089 USA.
   [Zhang, Hao F.] Northwestern Univ, Dept Ophthalmol, Evanston, IL 60208 USA.
C3 Northwestern University; Harbin Institute of Technology; University of
   Southern California; Northwestern University
RP Zhang, HF (通讯作者)，Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA.
EM hfzhang@northwestern.edu
RI Jiao, Shuliang/I-8153-2015; Zhang, Hao F F/C-2451-2015; Zhang, Hao
   F/D-1695-2011
OI Zhang, Hao F F/0000-0001-5089-1196; 
FU National Science Foundation [CBET-1055379]; National Institutes of
   Health [1RC4EY021357, 1R01EY019951]; China Scholarship Council; NATIONAL
   EYE INSTITUTE [RC4EY021357, R01EY019951] Funding Source: NIH RePORTER
FX We thank the generous support from the National Science Foundation
   (CAREER CBET-1055379) and the National Institutes of Health
   (1RC4EY021357, 1R01EY019951). We also acknowledge the support from the
   China Scholarship Council to Wei Song.
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NR 15
TC 17
Z9 19
U1 0
U2 22
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD JAN
PY 2013
IS 71
AR e4390
DI 10.3791/4390
PG 5
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA V36QO
UT WOS:000209226200017
PM 23354081
OA Green Published
DA 2022-11-30
ER

PT J
AU Striker, GE
   Praddaude, F
   Alcazar, O
   Cousins, SW
   Marin-Castano, ME
AF Striker, Gary E.
   Praddaude, Francoice
   Alcazar, Oscar
   Cousins, Scott W.
   Marin-Castano, Maria E.
TI Regulation of angiotensin II receptors and extracellular matrix turnover
   in human retinal pigment epithelium: role of angiotensin II
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE calcium; hypertension; Bruch's membrane
ID NONLETHAL OXIDANT INJURY; RENIN MESSENGER-RNA; COLLAGEN PRODUCTION;
   GROWTH-FACTOR; MACULAR DEGENERATION; CARDIAC FIBROBLASTS; CONVERTING
   ENZYME; TISSUE INHIBITOR; TGF-BETA; IN-VITRO
AB Striker GE, Praddaude F, Alcazar O, Cousins SW, Marin-Castano ME. Regulation of angiotensin II receptors and extracellular matrix turnover in human retinal pigment epithelium: role of angiotensin II. Am J Physiol Cell Physiol 295: C1633-C1646, 2008. First published October 15, 2008; doi:10.1152/ajpcell.00092.2008.-The early stage of age-related macular degeneration (AMD) is characterized by the formation of subretinal pigment epithelium (RPE) deposits as a result of the dysregulation in the turnover of extracellular matrix (ECM) molecules. However, the mechanism involved remains unclear. Hypertension (HTN) is an important risk factor for AMD, and angiotensin II (ANG II) is the most important hormone associated with HTN. However, the relevance of ANG II receptors and ANG II effects on RPE have not been investigated yet. Therefore, the expression and regulation of ANG II receptors as well as the ECM turnover were studied in human RPE. ANG II receptors were expressed and upregulated by ANG II in human RPE. This regulation resulted in functional receptor expression, since an increase in intracellular concentration of calcium was observed upon ANG II stimulation. ANG II also increased matrix metalloproteinase (MMP)-2 activity and MMP-14 at the mRNA and protein levels as well as type IV collagen degradation. These ANG II effects were abolished in the presence of the ANG II receptor subtype 1 (AT1) receptor antagonist candesartan. In contrast, ANG II decreased type IV collagen via both AT1 and AT2 receptors, suggesting a synergistic effect of the two receptor subtypes. In conclusion, we have confirmed the presence of ANG II receptors in human RPE and their regulation by ANG II as well as the regulation of ECM molecules via ANG II receptors. Our data support the hypothesis that ANG II may exert biological function in RPE through ANG II receptors and that ANG II may cause dysregulation of molecules that play a major role in the turnover of ECM in RPE basement membrane and Bruch's membrane, suggesting a pathogenic mechanism to explain the link between HTN and AMD.
C1 [Alcazar, Oscar; Marin-Castano, Maria E.] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Striker, Gary E.] Mt Sinai Sch Med, Div Expt Diabet & Aging, New York, NY USA.
   [Praddaude, Francoice] Univ Toulouse 3, Sch Med, F-31062 Toulouse, France.
   [Cousins, Scott W.] Duke Univ, Ctr Eye, Duke Ctr Macular Dis, Durham, NC USA.
C3 Bascom Palmer Eye Institute; University of Miami; Icahn School of
   Medicine at Mount Sinai; Universite de Franche-Comte; Universite de
   Toulouse; Universite Toulouse III - Paul Sabatier; Duke University
RP Marin-Castano, ME (通讯作者)，Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami, FL 33136 USA.
EM mcastano@med.miami.edu
FU National Eye Institute [R01 EY015249-01A1, EY015249-01A1S1, EY014801];
   NATIONAL EYE INSTITUTE [P30EY014801, R01EY015249] Funding Source: NIH
   RePORTER
FX This study was supported by National Eye Institute Grants R01
   EY015249-01A1, EY015249-01A1S1, and EY014801.
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NR 81
TC 30
Z9 30
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
EI 1522-1563
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD DEC
PY 2008
VL 295
IS 6
BP C1633
EP C1646
DI 10.1152/ajpcell.00092.2008
PG 14
WC Cell Biology; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Physiology
GA 401AH
UT WOS:000262910000019
PM 18923060
OA Green Published
DA 2022-11-30
ER

PT J
AU Song, HG
   Moon, C
   Park, MH
   Moon, JI
   Moon, C
AF Song, Hyoung-Gon
   Moon, Cheil
   Park, Myoung-Hee
   Moon, Jung-Il
   Moon, Chanil
TI Decrease in intracellular glutathione level alters expressions of B-cell
   CLL/lymphoma 2 family members in the mouse retina
SO JOURNAL OF HEALTH SCIENCE
LA English
DT Article
DE oxidative stress; retina; glutathione; buthionine sulphoximine; B-cell
   CLL/lymphoma 2
ID NEURODEGENERATIVE DISORDERS; NEURONAL APOPTOSIS; NONNEURONAL CELLS;
   OXIDATIVE STRESS; IN-VIVO; BAX; SURVIVAL; DEPLETION; MICE; MITOCHONDRIA
AB Oxidative stress affects all intracellular macromolecules, and leads cells to death under unfavorable conditions. Glutathione (GSH) is known to play a critical role in the cellular defense against unregulated oxidative stress in mammalian cells including neurons. We previously demonstrated that GSH depletion induces cell death in the retina, but the mechanism of cell defense by GSH is still unclear. Thus, we here examined the effect of GSH depletion on expression of members of B-cell CLL/lymphoma 2 (Bcl-2) family (bcl-2. bcl-X-L, bax, bak, n-bak and bad) known to play key roles in determining cell viability. In order to deplete intracellular GSH, we systemically administrated buthionine sulphoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase to mice. After 0, 1, 4, and 7 days of BSO injection, total RNAs from retina of each animals were isolated and subjected to real-time reverse transcription (RT)-polymerase chain reaction (PCR) analysis. Expression of bcl-X-L increased one day after BSO injection, but was back to the basal level on day 4. Its expression decreased on day 7. Expressions of bcl-2 and bax were significantly decreased from 4 days after BSO injection, whereas expression of bad was not changed. An anti-apoptotic molecule, bak displayed a significant decrease 7 days after BSO injection, whereas neuronal cell specific Bak (Bcl-2 homologous, antagonist/killer), N-Bak was not altered in its gene expression. Taken together, we demonstrated that decrease in intracellular glutathione level altered expressions of Bcl-2 family members in distinct mariners. Our study implies a defensive mechanism of GSH against oxidative stress for retinal neuronal survival which may involve alteration of expression of Bcl-2 family members, especially Bcl-2 and Bcl-X-L. Thus, over-expression of Bcl-2 and Bcl-XL may not the only but a critical factor in GSH-dependent cellular protection, and which implies Bcl-2 and Bcl-X-L may provide a potent therapeutic tool for cures against oxidative stress induced retinal degenerative diseases such as glaucoma, retinopathy, and age-related macular degeneration.
C1 [Moon, Chanil] Gachon Univ, Gil Med Ctr, Dept Cardiol, Inchon 405760, South Korea.
   [Song, Hyoung-Gon] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Emergency Med, Seoul 135710, South Korea.
   [Moon, Cheil] Kyungpook Natl Univ, Sch Dent, Dept Oral Anat & Neurobiol, Taegu 700412, South Korea.
   [Park, Myoung-Hee; Moon, Jung-Il] Catholic Univ Korea, Coll Med, Dept Ophthalmol, Seoul 150713, South Korea.
C3 Gachon University; Sungkyunkwan University (SKKU); Samsung Medical
   Center; Kyungpook National University; Catholic University of Korea
RP Moon, C (通讯作者)，Gachon Univ, Gil Med Ctr, Dept Cardiol, 1198 Guwol Dong, Inchon 405760, South Korea.
EM cmoon351@gmail.com
OI Moon, Cheil/0000-0002-9741-7229
FU Korea Science & Engineering Foundation [R01-2006-000-10488-0]
FX This work was supported by grant No. R01-2006-000-10488-0 from the Basic
   Research Program of the Korea Science & Engineering Foundation (CM).
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NR 42
TC 2
Z9 2
U1 0
U2 5
PU PHARMACEUTICAL SOC JAPAN
PI TOKYO
PA 2-12-15-201 SHIBUYA, SHIBUYA-KU, TOKYO, 150, JAPAN
SN 1344-9702
J9 J HEALTH SCI
JI J. Health Sci.
PD AUG
PY 2008
VL 54
IS 4
BP 464
EP 470
DI 10.1248/jhs.54.464
PG 7
WC Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Toxicology
GA 347UE
UT WOS:000259165800013
OA Bronze
DA 2022-11-30
ER

PT J
AU Grant, SF
   Baldassano, RN
   Hakonarson, H
AF Grant, Struan Fa
   Baldassano, Robert N.
   Hakonarson, Hakon
TI Classification of genetic profiles of Crohn's disease: a focus on the
   ATG16L1 gene
SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
LA English
DT Review
DE ATG16L1; autophagy-related 16-like 1 gene; Crohn's disease; genome-wide
   association; single nucleotide polymorphism
ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; ULCERATIVE-COLITIS;
   CLINICAL CHARACTERISTICS; SUSCEPTIBILITY LOCI; CHINESE POPULATION;
   ADAPTIVE IMMUNITY; COMPLEX DISEASES; HAPLOTYPE MAP; RISK LOCI
AB inflammatory bowel disease constitutes two related clinical entities, Crohn's disease (CD) and ulcerative colitis (UC), both of which have increased in prevalence over the last decade. Family and twin studies have strongly indicated that genetic factors play a large role in an individual's risk of developing inflammatory bowel disease. Despite this, it has proven difficult to isolate disease genes that confer susceptibility to this disease using classical candidate gene and linkage approaches, with the notable exception of the isolation of the caspase recruitment domain family, member 15 (CARD15) gene. However, over the last 2 years, genome-wide association (GWA) studies have become feasible, where modern high-throughput single nucleotide polymorphism (SNP) genotyping technologies can be applied to large and comprehensively phenotyped patient cohorts. Such approaches have enabled scientists to robustly associate specific variants with many complex diseases, including age-related macular degeneration, Type 2 diabetes, breast cancer and asthma. in the inflammatory bowel disease field, positive associations with CD and UC coming from GWA studies have been reported for an ever increasing number of genes. The most consistently and strongly associated variants have been in the GARD15, the interleukin 23 receptor (IL23R) and autophagy-related 16-like 1 (ATG16L1) genes. With respect to ATG16L1, the G allele of SNP rs2241880 has been shown in multiple association studies to confer strong risk for CD, although its association with UC remains more debatable. This SNP is in fact a common coding variant, specifically a threonine-to-alanine substitution at amino acid position 300 of the ATG16L1 protein (T300A), and appears to account for all of the disease risk conferred by this locus. This review addresses recent advances in GWA studies of inflammatory bowel disease, with specific focus on the growing evidence of the ATG16L1 gene's role in CD and how its protein product operating within the autophagic pathway makes autophagy an attractive therapeutic target for this debilitating disorder.
C1 [Grant, Struan Fa; Hakonarson, Hakon] 1216F Abramson Res Ctr, Ctr Appl Genom, Div Human Genet, Philadelphia, PA 19104 USA.
   [Grant, Struan Fa] Childrens Hosp Philadelphia, 1216F Abramson Res Ctr, Abramson Res Ctr, Joseph Stokes Jr Res Inst,Dept Pediat, Philadelphia, PA 19104 USA.
   [Grant, Struan Fa] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
   [Baldassano, Robert N.] Ctr Pediat Inflammatory Bowel Dis, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA.
   [Baldassano, Robert N.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
   [Hakonarson, Hakon] Childrens Hosp Philadelphia, 1216E Abramson Res Ctr, Div Human Genet,Dept Pediat, Abramson Res Ctr,Joseph Stokes Jr Res Inst, Philadelphia, PA 19104 USA.
   [Hakonarson, Hakon] Ctr Appl Genom, Philadelphia, PA 19104 USA.
   [Hakonarson, Hakon] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of
   Philadelphia; University of Pennsylvania; University of Pennsylvania;
   Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of
   Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia;
   University of Pennsylvania
RP Hakonarson, H (通讯作者)，1216F Abramson Res Ctr, Ctr Appl Genom, Div Human Genet, 3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM grants@chop.edu; hakonarson@chop.edu
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NR 89
TC 7
Z9 8
U1 1
U2 5
PU TAYLOR & FRANCIS AS
PI OSLO
PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY
SN 1473-7159
EI 1744-8352
J9 EXPERT REV MOL DIAGN
JI Expert Rev. Mol. Diagn.
PD MAR
PY 2008
VL 8
IS 2
BP 199
EP 207
DI 10.1586/14737159.8.2.199
PG 9
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 289OZ
UT WOS:000255065100008
PM 18366306
DA 2022-11-30
ER

PT J
AU Frennesson, C
   Nilsson, SE
AF Frennesson, Christina
   Nilsson, Sven Erik
TI The superior retina performs better than the inferior retina when
   reading with eccentric viewing: a comparison in normal volunteers
SO ACTA OPHTHALMOLOGICA SCANDINAVICA
LA English
DT Article
DE reading; eccentric viewing; superior and inferior retina; normal
   volunteers; scanning laser ophthalmoscope
ID VISION
AB Purpose: Patients with an absolute central scotoma, such as in age-related macular degeneration, need to use eccentric viewing for reading. In the present study, we investigated whether there are differences in reading performance between the superior and inferior retina.
   Methods: Twelve volunteers with normal vision, aged 25-58 years and able to maintain stable eccentric viewing, were studied in a scanning laser ophthalmoscope while reading a line of text, 6 degrees above or below a fixation line (series A). The text, properly magnified above threshold, was scrolled at a speed of 60 words/min. The number of words missed or incorrectly read in 1 min as well as words read when occasionally fixating the text was counted. In series B, a random letter text was superimposed upon the fixation line (i. e. at 6 degrees from the original line of text) to see whether this would disturb reading. In series C, the random letter text was moved away from the fixation line to a distance of 12 degrees from the original line of text. The entire programme was repeated in reverse order, and the mean value of the two series was used for calculations, which were carried out using Student's two-sided t-test.
   Results: In all series of experiments, the number of errors was significantly lower when using the superior retina compared with the inferior retina (A: p = 0.006; B: p = 0.042, C: p = 0.009). The addition of the random letter line of text at 6 or 12 degrees did not disturb reading performance significantly. There was no significant difference between the superior and inferior retina in terms of visual acuity.
   Conclusions: In eccentric viewing, reading performance was significantly better when using the superior retina compared with the inferior retina. A line of random letter text at a distance of 6 or 12 degrees from the original line of text did not disturb reading significantly.
C1 Linkoping Univ, Dept Ophthalmol, S-58185 Linkoping, Sweden.
C3 Linkoping University
RP Frennesson, C (通讯作者)，Linkoping Univ, Dept Ophthalmol, S-58185 Linkoping, Sweden.
EM Christina.Frennesson@lio.se
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NR 5
TC 17
Z9 17
U1 0
U2 2
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1395-3907
J9 ACTA OPHTHALMOL SCAN
JI Acta Ophthalmol. Scand.
PD DEC
PY 2007
VL 85
IS 8
BP 868
EP 870
DI 10.1111/j.1600-0420.2007.00984.x
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 232MY
UT WOS:000251025000012
PM 17651472
OA Bronze
DA 2022-11-30
ER

PT J
AU Shakoor, SA
   Rahman, M
   Hossain, AHME
   Moniruzzaman, M
   Bhuiyan, MR
   Hakim, F
   Zaman, MM
AF Shakoor, Shawkat Ara
   Rahman, Mustafizur
   Hossain, A. H. M. Enayet
   Moniruzzaman, Mohammad
   Bhuiyan, Mahfuzur Rahman
   Hakim, Ferdous
   Zaman, M. Mostafa
TI Prevalence of blindness and its determinants in Bangladeshi adult
   population: results from a national cross-sectional survey
SO BMJ OPEN
LA English
DT Article
DE cataract and refractive surgery; glaucoma; epidemiology; ophthalmology;
   corneal and external diseases
ID VISUAL IMPAIRMENT; LOW-VISION; DIABETIC-RETINOPATHY; URBAN-POPULATION;
   SOUTHERN INDIA; PREVENTION
AB Objective The objective of this study was to determine the prevalence of blindness and its determinants in Bangladeshi adult population. Study design A cross-sectional population-based survey conducted at household level with national representation. Samples were drawn from the 2011 national census frame using a multistage stratified cluster sampling method. Setting and participants The survey was done in urban and rural areas in 2013 using a probability proportionate to size sampling approach to locate participants from 72 primary sampling units. One man or one woman aged >= 40 years was randomly selected from their households to recruit 7200. In addition to sociodemographic data, information on medication for hypertension and diabetes was obtained. Blood pressure and capillary blood glucose were measured. Eyelids, cornea, lens, and retina were examined in addition to visual acuity and refraction testing. Primary outcome measures The following definition was used to categorise subjects having (1) blindness: visual acuity <3/60, (2) low vision: >= 3/60 to <6/60 and (3) normal vision: >= 6/12 after best correction. Results We could recruit 6391 (88.8%) people among whom 2955 (46.2%) were men. Among them, 1922 (30.1%) were from urban and 4469 (69.9%) were from rural areas. The mean age was 54.3 (SD 11.2) years. The age-standardised prevalence, after best correction, of blindness and low vision was 1.0% (95% CI 0.5% to 1.4%) and 12.1% (95% CI 10.5% to 13.8%), respectively. Multivariable logistic regression indicated that cataract, age-related macular degeneration and diabetic retinopathy were significantly associated with low vision and blindness after adjustment for age and sex. Population attributable risk of cataract for low vision and blindness was 79.6%. Conclusions Low vision and blindness are common problems in those aged 40 years or older. Extensive screening and eye care services are necessary for wider coverage engaging all tiers of the healthcare system especially focusing on cataract.
C1 [Shakoor, Shawkat Ara] Natl Inst Ophthalmol, Community Ophtalmol, Dhaka, Bangladesh.
   [Rahman, Mustafizur] Dhaka Med Coll, Ophthalmol, Dhaka, Bangladesh.
   [Hossain, A. H. M. Enayet] Natl Inst Opthalmol, Paediat Ophthalmol, Dhaka, Bangladesh.
   [Moniruzzaman, Mohammad] Shiga Univ Med Sci, Publ Hlth, Otsu, Shiga, Japan.
   [Bhuiyan, Mahfuzur Rahman] Natl Heart Fdn Hosp & Res Inst, Epidemiol & Res, Dhaka, Bangladesh.
   [Hakim, Ferdous; Zaman, M. Mostafa] WHO, Res & Publicat, Dhaka, Bangladesh.
C3 Dhaka Medical College; Shiga University of Medical Science; World Health
   Organization
RP Zaman, MM (通讯作者)，WHO, Res & Publicat, Dhaka, Bangladesh.
EM zamanm@who.int
RI Hakim, Ferdous/GXF-2130-2022; Moniruzzaman, Mohammad/H-8503-2019; Zaman,
   M Mostafa/H-5155-2019
OI Hakim, Ferdous/0000-0003-2376-3978; Moniruzzaman,
   Mohammad/0000-0003-2144-7111; Shakoor, Shawkat Ara/0000-0001-6299-7529;
   Hussain, AHM Enayet/0000-0003-2715-5574; Bhuiyan, Mahfuzur
   Rahman/0000-0001-6962-7264; Zaman, M Mostafa/0000-0002-1736-1342
FU WHO Country Office for Bangladesh [2013/355662-0, 200843353,
   BAN-2013-B7-TSA-0001]
FX The WHO Country Office for Bangladesh provided financial assistance for
   this study (WHO Reference: 2013/355662-0, Purchase Order: 200843353,
   Reg. File: BAN-2013-B7-TSA-0001). However, no fund was used in preparing
   this manuscript.
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NR 36
TC 0
Z9 0
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PD APR
PY 2022
VL 12
IS 4
AR e052247
DI 10.1136/bmjopen-2021-052247
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 0G4ZJ
UT WOS:000778054700015
PM 35365514
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wagner, N
   Reinehr, S
   Gammel, MR
   Greulich, A
   Hurst, J
   Dick, HB
   Schnichels, S
   Joachim, SC
AF Wagner, Natalie
   Reinehr, Sabrina
   Gammel, Maurice R.
   Greulich, Andrea
   Hurst, Jose
   Dick, H. Burkhard
   Schnichels, Sven
   Joachim, Stephanie C.
TI Novel Porcine Retina Cultivation Techniques Provide Improved
   Photoreceptor Preservation
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE age-related macular degeneration; porcine; photoreceptor; optical
   coherence tomography; organotypic retina culture; opsin; rhodopsin
ID MACULAR DEGENERATION; ULTRASTRUCTURAL-CHANGES; COHERENCE TOMOGRAPHY;
   GENE-EXPRESSION; ORGAN-CULTURE; MOUSE MODEL; IN-VIVO; PREVALENCE; CELLS;
   DEPOSITS
AB Age-related macular degeneration (AMD) is the leading cause of blindness in industrialized countries among people over 60 years. It has multiple triggers and risk factors, but despite intense research efforts, its pathomechanisms are currently not completely understood. AMD pathogenesis is characterized by soft drusen in Bruch's membrane and involves the retinal pigment epithelium-Bruch's membrane-choroid complex and adjacent structures, like photoreceptors. This study explores the potential of novel cultivation techniques to preserve photoreceptors in retinal explants to gain better insights in AMD pathology. The porcine retina explants were cultured for 4 and 8 days using three different explantation techniques, namely, control (photoreceptors facing down, touching the filter), filter (photoreceptors facing up, turned sample using a filter), and tweezers (photoreceptors facing up, turned sample using tweezers). Optical coherence tomography revealed that the tweezers method had the best capacity to limit thinning of the retinal explants. Both novel methods displayed advantages in maintaining outer segment thickness. Additionally, immunofluorescence evaluation revealed a better preservation of opsin(+)cells and rhodopsin signal intensity in both novel methods, especially the tweezers method. Furthermore, RT-qPCR analysis demonstrated an upregulation ofOPSINandRHODOPSINmRNA expression in tweezers samples at 8 days. Amacrine and bipolar cell numbers were not altered at day 4 of cultivation, while cultivation until 8 days led to reduced bipolar cell numbers. At 4 days,CALRETININmRNA was upregulated in filter samples, butprotein kinase C alphaexpression was downregulated. Retinal ganglion cells were diminished in both novel techniques due to a direct physical contact with the insert. Remarkably, no difference inTUBB3mRNA expression was detected among the techniques. Nevertheless, both novel methods exhibited an improved retention of photoreceptor cells. In conclusion, the tweezers technique was the most promising one. Due to the high homology of the porcine to the human retina, it provides a reasonable alternative toin vivorodent models. Consequently, an adapted coculture system based on the current findings may serve as anex vivomodel suitable to analyze AMD pathomechanisms and novel therapeutic approaches.
C1 [Wagner, Natalie; Reinehr, Sabrina; Gammel, Maurice R.; Greulich, Andrea; Dick, H. Burkhard; Joachim, Stephanie C.] Ruhr Univ Bochum, Univ Eye Hosp, Expt Eye Res Inst, Bochum, Germany.
   [Hurst, Jose; Schnichels, Sven] Univ Eye Hosp, Ctr Ophthalmol, Tubingen, Germany.
C3 Ruhr University Bochum; Eberhard Karls University of Tubingen; Eberhard
   Karls University Hospital
RP Joachim, SC (通讯作者)，Ruhr Univ Bochum, Univ Eye Hosp, Expt Eye Res Inst, Bochum, Germany.
EM stephanie.joachim@rub.de
RI Joachim, Stephanie/AAV-5980-2021
OI Schnichels, Sven/0000-0002-2385-5517
FU PRO RETINA-Foundation for Prevention of Blindness; Novartis Pharma GmbH;
   DFG Open Access Publication Funds of the Ruhr-Universitat Bochum
FX This study was in part supported by PRO RETINA-Foundation for Prevention
   of Blindness and Novartis Pharma GmbH. We acknowledged the support by
   the DFG Open Access Publication Funds of the Ruhr-Universitat Bochum.
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NR 62
TC 6
Z9 6
U1 0
U2 3
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD OCT 6
PY 2020
VL 14
AR 556700
DI 10.3389/fnins.2020.556700
PG 15
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA OC9NH
UT WOS:000579481000001
PM 33122987
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Chen, XY
   Singh, D
   Adelman, RA
   Rizzolo, LJ
AF Chen, Xiaoyu
   Singh, Deepti
   Adelman, Ron A.
   Rizzolo, Lawrence J.
TI Unstimulated, Serum-free Cultures of Retinal Pigment Epithelium Excrete
   Large Mounds of Drusen-like Deposits
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Retinal pigment epithelium; drusen; macular degeneration; cell culture;
   retinal progenitor cells; human induced pluripotent cells
ID EMBRYONIC STEM-CELLS; MACULAR DEGENERATION; COMPLEMENT ACTIVATION; AGE;
   DIFFERENTIATION; HYPOTHESIS
AB Purpose: A hallmark of age-related macular degeneration is the accumulation of deposits of lipids and proteins, called drusen, in Bruch's membrane. Several culture models of retinal pigment epithelia (RPE) develop drusen-like deposits. We examined whether prolonged culture of RPE with a retina-like tissue affected the number or size of these deposits. Methods: RPE and retinal progenitor cells (RPC) were differentiated from induced pluripotent stem cells derived from fetal tissue and maintained in serum-free medium containing the B27 supplement. RPE was cultured on Transwell filter inserts, and RPC were cultured on a planar matrix composed of gelatin, hyaluronic acid, and chondroitin sulfate. After seeding the filter, RPC were layered on top of the RPE. RPE +/- RPC were cultured for six months. The function of RPE tight junctions was assessed by the transepithelial electrical resistance. Cultures were stained for actin, neutral lipids, APOE, TIMP3, vitronectin, and calcium deposits. Morphometric analysis was used to determine the number and volume of the "druse". Results: After six months, the TER was greater for the co-cultures (304 +/- 11 omega x cm(2) vs 243 +/- 7 omega x cm(2), p < .01). RPE formed mounds of druse-like deposits that contained, vitronectin, APOE, TIMP3 and calcium deposits, but lipids were undetected. The mounds overlay areas of the filter where no lipid was detected in the pores, and the RPE overlying the mounds was often thin. The number of "druse"/100,000 mu m(2) was 5.0 +/- 0.4 (co-cultures) vs 2.3 +/- 0.1 (monocultures) (p < .05). The total volume of "drusen"/100,000 mu m(3) was 15,133 +/- 1544 (co-cultures) vs 5,993 +/- 872 (monocultures) (p < .05). There was no statistical difference between the size-distribution of druse-like particles formed by each culture. Conclusions: Covering the apical membrane of RPE with a thick tissue increased the number of druse-like deposits. The apparent size limitation of the deposits may reflect the apparent interruption of the of lipid cycle found at the basal membrane of the RPE.
C1 [Chen, Xiaoyu; Singh, Deepti; Rizzolo, Lawrence J.] Yale Univ, Dept Surg, New Haven, CT USA.
   [Chen, Xiaoyu; Singh, Deepti; Adelman, Ron A.; Rizzolo, Lawrence J.] Yale Univ, Dept Ophthalmol & Visual Sci, New Haven, CT USA.
   [Chen, Xiaoyu] Cent South Univ, Dept Ophthalmol, Second Xiangya, Changsha, Hunan, Peoples R China.
C3 Yale University; Yale University; Central South University
RP Rizzolo, LJ (通讯作者)，Yale Univ, Sch Med, Dept Surg, POB 208062, New Haven, CT 06520 USA.
EM Lawrence.rizzolo@yale.edu
RI Singh, Deepti/ABC-1159-2021
OI Singh, Deepti/0000-0003-3302-2110; Rizzolo, Lawrence/0000-0002-2393-8419
FU Alonzo Family Fund; Newman's Own Foundation; Leir; Research to Prevent
   Blindness (Yale University)
FX This work was supported by grants from the Alonzo Family Fund (LJR);
   Newman's Own Foundation (RAA); Leir (RAA); and Research to Prevent
   Blindness (Yale University).
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NR 23
TC 6
Z9 6
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD NOV 1
PY 2020
VL 45
IS 11
BP 1390
EP 1394
DI 10.1080/02713683.2020.1740744
EA MAR 2020
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OA2AY
UT WOS:000523756300001
PM 32202447
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Wang, Y
   Tran, T
   Firl, K
   Huang, N
   Yasin, O
   van Kuijk, FJGM
   Montezuma, SR
AF Wang, Yao
   Tran, Tu
   Firl, Kevin
   Huang, Natalie
   Yasin, Omar
   van Kuijk, Frederik J. G. M.
   Montezuma, Sandra R.
TI Quantitative fundus autofluorescence in smokers compared to non-smokers
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Smoking; Fundus autofluorescence;
   Ophthalmic imaging; Lipofuscin
ID RETINAL-PIGMENT EPITHELIUM; OPTICAL COHERENCE TOMOGRAPHY; GEOGRAPHIC
   ATROPHY SECONDARY; MACULAR DEGENERATION; RPE LIPOFUSCIN; AGE;
   ASSOCIATION; RISK; BISRETINOIDS; PROGRESSION
AB Increased fundus autofluorescence is directly related to increased RPE lipofuscin deposition in the retina and has been observed in eyes with age-related macular degeneration (AMD). Smoking is the most significant modifiable risk factor for the development and progression of AMD, in which one of the main mechanisms is oxidative damage from smoking leading to RPE cell toxicity. The relationship between smoking and autofluorescence is not established and could provide insight into pathogenic mechanism of AMD. Therefore, our objective was to compare quantitative fundus autofluorescence (qAF) in the retinae of healthy non-smokers to smokers. We conducted a cross-sectional study at the 2016 Minnesota State Fair. Participants self-reported past medical and ocular history and underwent eye examination as well as qAF imaging with Spectralis confocal scanning laser ophthalmoscope (cSLO) equipped with an internal fluorescent reference. Two sets of images were obtained per eye. Stepwise multiple mixed effects regression model was used to examine the relationship between mean qAF values and smoking status. We enrolled 105 individuals (54 smokers, 61 females, mean age 41 years with range 18-78 years old). Fundus autofluorescence images were analyzable for 85 of 105 individuals contributing 161 eyes (80 right, 81 left). The repeatability coefficients between the first set and second set of images were +/- 21% of their mean qAF values. Older age and female gender were independently associated with higher qAF. Positive smoking history tended to result in higher qAF values after adjusting for age and gender but was not statistically significant (0.118, 95%CI -0.003, 0.240, P = 0.056). Among smokers, the number of pack-years smoked was not significantly associated with higher qAF. Our study's results are consistent with existing literature in which older age is predictive of intensified autofluorescence, while smoking history does not have as important of an impact on autofluorescence as hypothesized. Several large epidemiological studies have shown that smoking is significantly associated with AMD, and qAF is likely not the appropriate modality to clinically assess smoking's impact on retinae.
C1 [Wang, Yao; Tran, Tu; Firl, Kevin; Huang, Natalie; van Kuijk, Frederik J. G. M.; Montezuma, Sandra R.] Univ Minnesota, Dept Ophthalmol & Visual Neurosci, MMC 493,420 Delaware St SE, Minneapolis, MN 55455 USA.
   [Yasin, Omar] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
C3 University of Minnesota System; University of Minnesota Twin Cities;
   Mayo Clinic
RP Montezuma, SR (通讯作者)，Univ Minnesota, Dept Ophthalmol & Visual Neurosci, MMC 493,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM smontezu@umn.edu
FU Minnesota Lions Vision Foundation; VitreoRetinal Surgery Foundation;
   Research to Prevent Blindness (RPB), New York, NY, USA
FX Sponsorship and article processing charges for this study were funded by
   the Minnesota Lions Vision Foundation, the VitreoRetinal Surgery
   Foundation, and an unrestricted grant to the Department of Ophthalmology
   and Visual and Neurosciences from the Research to Prevent Blindness
   (RPB), New York, NY, USA.
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NR 46
TC 6
Z9 6
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUL
PY 2019
VL 184
BP 48
EP 55
DI 10.1016/j.exer.2019.04.004
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IF3ND
UT WOS:000472986600007
PM 30991052
DA 2022-11-30
ER

PT J
AU Hollingworth, W
   Jones, T
   Reeves, BC
   Peto, T
AF Hollingworth, William
   Jones, Tim
   Reeves, Barnaby C.
   Peto, Tunde
TI A longitudinal study to assess the frequency and cost of antivascular
   endothelial therapy, and inequalities in access, in England between 2005
   and 2015
SO BMJ OPEN
LA English
DT Article
ID MACULAR DEGENERATION; INTRAVITREAL INJECTIONS; BEVACIZUMAB; RANIBIZUMAB;
   AFLIBERCEPT; TRENDS; EDEMA; RATES; TIME
AB Objectives High-cost antivascular endothelial growth factor (anti-VEGF) medicines for eye disorders challenge ophthalmologists and policymakers to provide fair access for patients while minimising costs. We describe the growth in the use and costs of these medicines and measure inequalities in access.
   Design Longitudinal study using Hospital Episode Statistics (2005/2006 to 2014/2015) and hospital prescribing cost reports (2008/2009 to 2015/2016). We used Poisson regression to estimate standardised rates and explore temporal and geographical variations.
   Setting National Health Service (NHS) care in England.
   Population Patients receiving anti-VEGF injections for age-related macular degeneration, diabetic macular oedema and other eye disorders.
   Interventions Higher-cost drugs (ranibizumab or aflibercept) recommended by the National Institute for Health and Care Excellence or lower-cost drug (bevacizumab) not licensed for eye disorders.
   Main outcome measures National procedure rates and variation between and within clinical commissioning groups (CCGs). Cost of ranibizumab and aflibercept prescribing.
   Results Injection procedures increased by 215% between 2010/2011 and 2014/2015. In 2014/2015 there were 388 031 procedures (714 per 100 000). There is no evidence that the dramatic growth in rates is slowing down. Since 2010/2011 the estimated cost of ranibizumab and aflibercept increased by 247% to 447 pound million in 2015/2016, equivalent to the entire annual budget of a CCG. There are large inequalities in access; in 2014/2015 procedure rates in a 'high use' CCG were 9.08 times higher than in a 'low use' CCG. In the South-West of England there was twofold variation in injections per patient per year (range 2.9 to 5.9).
   Conclusions The high and rising cost of anti-VEGF therapy affects the ability of the NHS to provide care for other patients. Current regulations encourage the increasing use of ranibizumab and aflibercept rather than bevacizumab, which evidence suggests is more cost-effective. NHS patients in England do not have equal access to the most cost-effective care.
C1 [Hollingworth, William] Univ Bristol, Dept Populat Hlth Sci, Bristol, Avon, England.
   [Jones, Tim] Univ Hosp Bristol NHS Fdn Trust, NIHR CLAHRC West, Bristol, Avon, England.
   [Reeves, Barnaby C.] Univ Bristol, Dept Translat Sci, Clin Trials Evaluat Unit, Bristol, Avon, England.
   [Peto, Tunde] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland.
C3 University of Bristol; University of Bristol; University of Bristol;
   Queens University Belfast
RP Hollingworth, W (通讯作者)，Univ Bristol, Dept Populat Hlth Sci, Bristol, Avon, England.
EM william.hollingworth@bristol.ac.uk
RI Peto, Tunde/G-8812-2018; Jones, Timothy/AAH-5671-2019
OI Peto, Tunde/0000-0001-6265-0381; Jones, Timothy/0000-0002-1199-8668;
   Hollingworth, William/0000-0002-0840-6254; Reeves,
   Barnaby/0000-0002-5101-9487
FU National Institute for Health Research Collaboration for Leadership in
   Applied Health Research and Care (NIHR CLAHRC) West
FX WH and TJ receive funding from the National Institute for Health
   Research Collaboration for Leadership in Applied Health Research and
   Care (NIHR CLAHRC) West.
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NR 40
TC 24
Z9 24
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PD OCT
PY 2017
VL 7
IS 10
AR e018289
DI 10.1136/bmjopen-2017-018289
PG 10
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA FS7VN
UT WOS:000422617500234
PM 29061629
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Stopa, M
   Marciniak, E
   Rakowicz, P
   Stankiewicz, A
   Marciniak, T
   Dabrowski, A
AF Stopa, Marcin
   Marciniak, Elzbieta
   Rakowicz, Piotr
   Stankiewicz, Agnieszka
   Marciniak, Tomasz
   Dabrowski, Adam
TI IMAGING AND MEASUREMENT OF THE PRERETINAL SPACE IN VITREOMACULAR
   ADHESION AND VITREOMACULAR TRACTION BY A NEW SPECTRAL DOMAIN OPTICAL
   COHERENCE TOMOGRAPHY ANALYSIS
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE vitreomacular interface; preretinal space; vitreomacular adhesion;
   vitreomacular traction; optical coherence tomography; image analysis
ID VITREORETINAL INTERFACE; THERAPY; SEGMENTATION; RANIBIZUMAB;
   OCRIPLASMIN; INJECTION; OUTCOMES; EDEMA
AB Purpose: To evaluate a new method for volumetric imaging of the preretinal space (also known as the subhyaloid, subcortical, or retrocortical space) and investigate differences in preretinal space volume in vitreomacular adhesion (VMA) and vitreomacular traction (VMT).
   Methods: Nine patients with VMA and 13 with VMT were prospectively evaluated. Automatic inner limiting membrane line segmentation, which exploits graph search theory implementation, and posterior cortical vitreous line segmentation were performed on 141 horizontal spectral domain optical coherence tomography B-scans per patient. Vertical distances (depths) between the posterior cortical vitreous and inner limiting membrane lines were calculated for each optical coherence tomography B-scan acquired. The derived distances were merged and visualized as a color depth map that represented the preretinal space between the posterior surface of the hyaloid and the anterior surface of the retina. The early treatment d retinopathy study macular map was overlaid onto final virtual maps, and preretinal space volumes were calculated for each early treatment diabetic retinopathy study map sector.
   Results: Volumetric maps representing preretinal space volumes were created for each patient in the VMA and VMT groups. Preretinal space volumes were larger in all early treatment diabetic retinopathy study map macular regions in the VMT group compared with those in the VMA group. The differences reached statistical significance in all early treatment diabetic retinopathy study sectors, except for the superior outer macula and temporal outer macula where significance values were P = 0.05 and P = 0.08, respectively. Overall, the relative differences in preretinal space volumes between the VMT and VMA groups varied from 2.7 to 4.3 in inner regions and 1.8 to 2.9 in outer regions.
   Conclusion: Our study provides evidence of significant differences in preretinal space volume between eyes with VMA and those with VMT. This may be useful not only in the investigation of preretinal space properties in VMA and VMT, but also in other conditions, such as age-related macular degeneration, diabetic retinopathy, and central retinal vein occlusion.
C1 [Stopa, Marcin; Marciniak, Elzbieta; Rakowicz, Piotr] Poznan Univ Med Sci, Heliodor Swiecicki Univ Hosp, Clin Eye Unit, Ul Grunwaldzka 16-18, PL-60780 Poznan, Poland.
   [Stopa, Marcin; Marciniak, Elzbieta; Rakowicz, Piotr] Poznan Univ Med Sci, Heliodor Swiecicki Univ Hosp, Pediat Ophthalmol Serv, Ul Grunwaldzka 16-18, PL-60780 Poznan, Poland.
   [Stopa, Marcin; Rakowicz, Piotr] Poznan Univ Med Sci, Dept Optometry & Biol Visual Syst, Poznan, Poland.
   [Stankiewicz, Agnieszka; Marciniak, Tomasz; Dabrowski, Adam] Poznan Univ Tech, Fac Comp, Div Signal Proc & Elect Syst, Chair Control & Syst Engn, Poznan, Poland.
C3 Poznan University of Medical Sciences; Poznan University of Medical
   Sciences; Poznan University of Medical Sciences; Poznan University of
   Technology
RP Stopa, M (通讯作者)，Poznan Univ Med Sci, Heliodor Swiecicki Univ Hosp, Clin Eye Unit, Ul Grunwaldzka 16-18, PL-60780 Poznan, Poland.; Stopa, M (通讯作者)，Poznan Univ Med Sci, Heliodor Swiecicki Univ Hosp, Pediat Ophthalmol Serv, Ul Grunwaldzka 16-18, PL-60780 Poznan, Poland.
EM stopa@ump.edu.pl
RI Marciniak, Tomasz/L-4702-2014; Stankiewicz, Agnieszka Anna/E-4385-2013;
   Stankiewicz, Agnieszka/R-1919-2019; Stopa, Marcin/R-2772-2018
OI Marciniak, Tomasz/0000-0001-6035-7325; Stankiewicz, Agnieszka
   Anna/0000-0002-2983-897X; Stankiewicz, Agnieszka/0000-0002-2983-897X;
   Stopa, Marcin/0000-0001-9540-9500; Marciniak,
   Elzbieta/0000-0002-7009-0406
FU National Research Centre Poland [2014/15/N/ST6/00710]
FX Supported by the National Research Centre Poland as a part of research
   project No. 2014/15/N/ST6/00710.
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NR 29
TC 1
Z9 1
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD OCT
PY 2017
VL 37
IS 10
BP 1839
EP 1846
DI 10.1097/IAE.0000000000001439
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FI1GH
UT WOS:000411680300015
PM 28045789
DA 2022-11-30
ER

PT J
AU Michalewska, Z
   Michalewski, J
   Nawrocka, Z
   Dulczewska-Cichecka, K
   Nawrocki, J
AF Michalewska, Zofia
   Michalewski, Janusz
   Nawrocka, Zofia
   Dulczewska-Cichecka, Karolina
   Nawrocki, Jerzy
TI SUPRACHOROIDAL LAYER AND SUPRACHOROIDAL SPACE DELINEATING THE OUTER
   MARGIN OF THE CHOROID IN SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE swept-source OCT; lamina suprachoroidea; suprachoroidal space; optical
   coherence tomography; suprachoroidal layer; lamina fusca;
   choroidoscleral boundary
ID SCLERA; EYES; POSTERIOR
AB Purpose: To define the morphology of outer choroidal margins in swept-source optical coherence tomography.
   Methods: This is a prospective observational study of 180 eyes: 20 eyes of healthy volunteers, 20 eyes of myopic patients, and 20 eyes from each of the following groups: macular hole, lamellar macular hole, epiretinal membranes, drusen, dry age-related macular degeneration (AMD), neovascular AMD, and vitreomacular traction. A single 12-mm wide swept-source optical coherence tomography image for each of the examined eyes consisting of 1,024 A-scans has been created. The main outcome measure selected was to estimate the presence of suprachoroidal layer, as well as to estimate the ability to delineate the outer choroidoscleral boundary using the software available (DRI-OCT) and to determine its shape.
   Results: Suprachoroidal layer was observed in 5% of healthy emmetropic eyes, in 50% of eyes with full-thickness macular holes, and in 60% of eyes with vitreomacular traction syndrome. It was also present in 50% of eyes with dry AMD and in 20% of eyes with neovascular AMD. The outer margin of the choroid in all eyes of the healthy volunteers and in eyes with macular diseases has been delineated correctly. In all healthy and myopic eyes, we recognized the outer choroidoscleral boundary as having a regular shape following the natural oval contour of the globe. In eyes with epiretinal membranes, macular hole, vitreomacular traction, and AMD, the outer choroidoscleral boundary was irregular; the choroid varied in thickness from point to point.
   Conclusion: Swept-source optical coherence tomography enables exact visualization of the outer choroidoscleral boundary. Suprachoroidal layer consisting of two bands has been recognized, the upper of which is hyperreflective and the lower of which is hyporeflective. It may be supposed that the lower hyporeflective band corresponds to suprachoroidal space, which was not earlier visualized in vivo in eyes without choroidal effusion. Suprachoroidal layer in myopic and emmetropic healthy subjects has been rarely observed. We observed it more frequently in different macular diseases.
C1 [Michalewska, Zofia; Michalewski, Janusz; Nawrocka, Zofia; Nawrocki, Jerzy] Ophthalm Clin Jasne Blonia, Lodz, Poland.
   [Michalewska, Zofia; Michalewski, Janusz; Dulczewska-Cichecka, Karolina; Nawrocki, Jerzy] III Municipal Hosp K Jonscher, Ophthalm Dept, Lodz, Poland.
RP Michalewska, Z (通讯作者)，Klin Okulistyczna Jasne Blonia, Ul Rojna 90, PL-91162 Lodz, Poland.
EM zosia_n@yahoo.com
OI Nawrocka, Zofia Anna/0000-0001-8376-9218; Michalewski,
   Janusz/0000-0002-1516-6703
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NR 13
TC 20
Z9 22
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD FEB
PY 2015
VL 35
IS 2
BP 244
EP 249
DI 10.1097/IAE.0000000000000281
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CA2UU
UT WOS:000348764200012
PM 25102196
DA 2022-11-30
ER

PT J
AU Krause, TA
   Alex, AF
   Engel, DR
   Kurts, C
   Eter, N
AF Krause, Torsten A.
   Alex, Anne F.
   Engel, Daniel R.
   Kurts, Christian
   Eter, Nicole
TI VEGF-Production by CCR2-Dependent Macrophages Contributes to
   Laser-Induced Choroidal Neovascularization
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; BONE-MARROW; MACULAR DEGENERATION; DENDRITIC
   CELLS; BLOOD-VESSELS; AGE; MICROGLIA; RECEPTOR; EXPRESSION; MONOCYTES
AB Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF). Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF(+) phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF(+) microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Muller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source of VEGF in laser-induced choroidal neovascularization but suggest that the therapeutic efficacy of CCR2-inhibition might be limited.
C1 [Krause, Torsten A.; Engel, Daniel R.; Kurts, Christian] Rhein Freidrich Wilhelms Univ Bonn, Inst Expt Immunol, D-53113 Bonn, Germany.
   [Alex, Anne F.; Eter, Nicole] Univ Munster, Dept Ophthalmol, D-48149 Munster, Germany.
C3 University of Bonn; University of Munster
RP Kurts, C (通讯作者)，Rhein Freidrich Wilhelms Univ Bonn, Inst Expt Immunol, D-53113 Bonn, Germany.
EM ckurts@web.de
RI Engel, Daniel Robert/C-5945-2013
OI Engel, Daniel Robert/0000-0001-7301-353X
FU Deutsche Forschungsgemeinschaft [SFBTR57, KU1063/8, ET 29/7-1]
FX This study was supported by the Deutsche Forschungsgemeinschaft
   (SFBTR57, KU1063/8 and ET 29/7-1). The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 8
PY 2014
VL 9
IS 4
AR e94313
DI 10.1371/journal.pone.0094313
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AE7FA
UT WOS:000334160900115
PM 24714223
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Stein, JD
   Newman-Casey, PA
   Mrinalini, T
   Lee, PP
   Hutton, DW
AF Stein, Joshua D.
   Newman-Casey, Paula Anne
   Mrinalini, Tavag
   Lee, Paul P.
   Hutton, David W.
TI Cost-Effectiveness of Bevacizumab and Ranibizumab for Newly Diagnosed
   Neovascular Macular Degeneration
SO OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; PHOTODYNAMIC THERAPY; LASER PHOTOCOAGULATION;
   UTILITY ANALYSIS; PEGAPTANIB; ENDOPHTHALMITIS; VERTEPORFIN; IMPACT;
   MODEL; EYES
AB Purpose: We sought to determine the most cost-effective treatment for patients with newly diagnosed neovascular macular degeneration: monthly or as-needed bevacizumab injections, or monthly or as-needed ranibizumab injections.
   Design: Cost-effectiveness analysis.
   Participants: Hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration.
   Methods: Using a mathematical model with a 20-year time horizon, we compared the incremental cost-effectiveness of treating a hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration using monthly bevacizumab, as-needed bevacizumab, monthly ranibizumab, or as-needed ranibizumab. Data came from the Comparison of Age-related macular degeneration Treatment Trial (CATT), the Medicare Fee Schedule, and the medical literature.
   Main Outcome Measures: Costs, quality-adjusted life-years (QALYs), and incremental costs per QALY gained.
   Results: Compared with as-needed bevacizumab, the incremental cost-effectiveness ratio of monthly bevacizumab is $242 357/QALY. Monthly ranibizumab gains an additional 0.02 QALYs versus monthly bevacizumab at an incremental cost-effectiveness ratio of >$10 million/QALY. As-needed ranibizumab was dominated by monthly bevacizumab, meaning it was more costly and less effective. In sensitivity analyses assuming a willingness to pay of $100 000/QALY, the annual risk of serious vascular events would have to be >= 2.5 times higher with bevacizumab than that observed in the CATT trial for as-needed ranibizumab to have an incremental cost-effectiveness ratio of <$100 000/QALY. In another sensitivity analysis, even if every patient receiving bevacizumab experienced declining vision by 1 category (e. g., from 20/25-20/40 to 20/50-20/80) after 2 years but every patient receiving ranibizumab retained their vision level, as-needed ranibizumab would have an incremental cost-effectiveness ratio of $97 340/QALY.
   Conclusions: Even after considering the potential for differences in risks of serious adverse events and therapeutic effectiveness, bevacizumab confers considerably greater value than ranibizumab for the treatment of neovascular macular degeneration. (C) 2014 by the American Academy of Ophthalmology.
C1 [Stein, Joshua D.; Newman-Casey, Paula Anne; Lee, Paul P.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
   [Mrinalini, Tavag; Hutton, David W.] Univ Michigan, Dept Hlth Management & Policy, Ann Arbor, MI 48105 USA.
C3 University of Michigan System; University of Michigan; University of
   Michigan System; University of Michigan
RP Stein, JD (通讯作者)，Univ Michigan, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM jdstein@med.umich.edu
OI Newman-Casey, Paula Anne/0000-0002-0847-1929; Stein,
   Joshua/0000-0003-2937-6987
FU National Eye Institute [1K23EY019511-01]; National Institute of Diabetes
   and Digestive and Kidney Diseases [P30DK092926]; Research to Prevent
   Blindness "Physician Scientist" Award; Research to Prevent Blindness;
   NATIONAL EYE INSTITUTE [K23EY019511, K12EY022299] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY
   DISEASES [P30DK092926] Funding Source: NIH RePORTER
FX National Eye Institute K23 Mentored Clinician Scientist Award
   (1K23EY019511-01); Grant Number P30DK092926 from the National Institute
   of Diabetes and Digestive and Kidney Diseases; Research to Prevent
   Blindness "Physician Scientist" Award; and an unrestricted grant from
   Research to Prevent Blindness.
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NR 53
TC 59
Z9 59
U1 0
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD APR
PY 2014
VL 121
IS 4
BP 936
EP 945
DI 10.1016/j.ophtha.2013.10.037
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AE2MV
UT WOS:000333808100026
PM 24405740
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Renganathan, K
   Gu, JY
   Rayborn, ME
   Crabb, JS
   Salomon, RG
   Collier, RJ
   Kapin, MA
   Romano, C
   Hollyfield, JG
   Crabb, JW
AF Renganathan, Kutralanathan
   Gu, Jiayin
   Rayborn, Mary E.
   Crabb, John S.
   Salomon, Robert G.
   Collier, Robert J.
   Kapin, Michael A.
   Romano, Carmelo
   Hollyfield, Joe G.
   Crabb, John W.
TI CEP Biomarkers as Potential Tools for Monitoring Therapeutics
SO PLOS ONE
LA English
DT Article
ID 5-HT1A RECEPTOR AGONIST; TRAUMATIC BRAIN-INJURY; FACTOR-H POLYMORPHISM;
   FACTOR-KAPPA-B; MACULAR DEGENERATION; BRUCHS MEMBRANE;
   SUPEROXIDE-DISMUTASE; DONOR EYES; DAMAGE; RAT
AB Background: Carboxyethylpyrrole (CEP) adducts are oxidative modifications derived from docosahexaenoate-containing lipids that are elevated in ocular tissues and plasma in age-related macular degeneration (AMD) and in rodents exposed to intense light. The goal of this study was to determine whether light-induced CEP adducts and autoantibodies are modulated by pretreatment with AL-8309A under conditions that prevent photo-oxidative damage of rat retina. AL-8309A is a serotonin 5-HT1A receptor agonist.
   Methods: Albino rats were dark adapted prior to blue light exposure. Control rats were maintained in normal cyclic light. Rats were injected subcutaneously 3x with 10 mg/kg AL-8309A (2 days, 1 day and 0 hours) before light exposure for 6 h (3.1 mW/cm(2), lambda=450 nm). Animals were sacrificed immediately following light exposure and eyes, retinas and plasma were collected. CEP adducts and autoantibodies were quantified by Western analysis or ELISA.
   Results: ANOVA supported significant differences in mean amounts of CEP adducts and autoantibodies among the light + vehicle, light + drug and dark control groups from both retina and plasma. Light-induced CEP adducts in retina were reduced similar to 20% following pretreatment with AL-8309A (n = 62 rats, p = 0.006) and retinal CEP immunoreactivity was less intense by immunohistochemistry. Plasma levels of light-induced CEP adducts were reduced at least 30% (n = 15 rats, p = 0.004) by drug pretreatment. Following drug treatment, average CEP autoantibody titer in light exposed rats (n = 22) was unchanged from dark control levels, and similar to 20% (p = 0.046) lower than in vehicle-treated rats.
   Conclusions: Light-induced CEP adducts in rat retina and plasma were significantly decreased by pretreatment with AL-8309A. These results are consistent with and extend previous studies showing AL-8309A reduces light-induced retinal lesions in rats and support CEP biomarkers as possible tools for monitoring the efficacy of select therapeutics.
C1 [Renganathan, Kutralanathan; Gu, Jiayin; Rayborn, Mary E.; Crabb, John S.; Hollyfield, Joe G.; Crabb, John W.] Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
   [Renganathan, Kutralanathan; Gu, Jiayin; Rayborn, Mary E.; Crabb, John S.; Hollyfield, Joe G.; Crabb, John W.] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA.
   [Renganathan, Kutralanathan; Gu, Jiayin; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
   [Collier, Robert J.; Kapin, Michael A.; Romano, Carmelo; Crabb, John W.] Novartis Inst Biomed Res, Ft Worth, TX USA.
   [Hollyfield, Joe G.; Crabb, John W.] Case Western Reserve Univ, Dept Ophthalmol, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
   [Hollyfield, Joe G.; Crabb, John W.] Case Western Reserve Univ, Dept Mol Med, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
C3 Cleveland Clinic Foundation; Cleveland Clinic Foundation; Case Western
   Reserve University; Novartis; Case Western Reserve University; Cleveland
   Clinic Foundation; Case Western Reserve University; Cleveland Clinic
   Foundation
RP Crabb, JW (通讯作者)，Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM crabbj@ccf.org
OI Salomon, Robert/0000-0001-9456-3557
FU National Institutes of Health (NIH) [GM21249, EY14239, EY14240,
   EY15638]; Ohio Biomedical Research Technology Transfer grant [05-29];
   Research Center grant from The Foundation Fighting Blindness; Llura and
   Gordon Gund Foundation; Research to Prevent Blindness (RPB); Macular
   Vision Research Foundation award; RPB Senior Investigator Award;
   Steinbach Award; Alcon Research Ltd; Cleveland Clinic Foundation;
   NATIONAL EYE INSTITUTE [R24EY015638, R01EY014240, R01EY016813,
   R01EY014239, P30EY011373, R56EY014240, R21EY022134] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM021249]
   Funding Source: NIH RePORTER
FX This study was supported in part by National Institutes of Health (NIH)
   grants GM21249, EY14239, EY14240, EY15638, Ohio Biomedical Research
   Technology Transfer grant 05-29, a Research Center grant from The
   Foundation Fighting Blindness, the Llura and Gordon Gund Foundation, an
   unrestricted grant from Research to Prevent Blindness (RPB), a Macular
   Vision Research Foundation award to JGH, an RPB Senior Investigator
   Award to JWC, a Steinbach Award to JWC, Alcon Research Ltd, and The
   Cleveland Clinic Foundation. The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 56
TC 16
Z9 16
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 1
PY 2013
VL 8
IS 10
AR e76325
DI 10.1371/journal.pone.0076325
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 231OR
UT WOS:000325427100059
PM 24098476
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Li, X
   Cai, Y
   Wang, YS
   Shi, YY
   Hou, W
   Xu, CS
   Wang, HY
   Ye, Z
   Yao, LB
   Zhang, J
AF Li, Xia
   Cai, Yan
   Wang, Yu-Sheng
   Shi, Yuan-Yuan
   Hou, Wei
   Xu, Chun-Sheng
   Wang, Hai-Yan
   Ye, Zi
   Yao, Li-Bo
   Zhang, Jian
TI Hyperglycaemia Exacerbates Choroidal Neovascularisation in Mice via the
   Oxidative Stress-Induced Activation of STAT3 Signalling in RPE Cells
SO PLOS ONE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; AGE-RELATED MACULOPATHY; N-ACETYL-CYSTEINE;
   MACULAR DEGENERATION; RISK-FACTORS; VEGF EXPRESSION; PATHOGENESIS;
   COMPLICATIONS; EXPOSURE; MODEL
AB Choroidal neovascularisation (CNV) that occurs as a result of age-related macular degeneration (AMD) causes severe vision loss among elderly patients. The relationship between diabetes and CNV remains controversial. However, oxidative stress plays a critical role in the pathogenesis of both AMD and diabetes. In the present study, we investigated the influence of diabetes on experimentally induced CNV and on the underlying molecular mechanisms of CNV. CNV was induced via photocoagulation in the ocular fundi of mice with streptozotocin-induced diabetes. The effect of diabetes on the severity of CNV was measured. An immunofluorescence technique was used to determine the levels of oxidative DNA damage by anti-8- hydroxy-2-deoxyguanosine (8-OHdG) antibody, the protein expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and vascular endothelial growth factor (VEGF), in mice with CNV. The production of reactive oxygen species (ROS) in retinal pigment epithelial (RPE) cells that had been cultured under high glucose was quantitated using the 2',7'-dichlorofluorescein diacetate (DCFH-DA) method. p-STAT3 expression was examined using Western blot analysis. RT-PCR and ELISA processes were used to detect VEGF expression. Hyperglycaemia exacerbated the development of CNV in mice. Oxidative stress levels and the expression of p-STAT3 and VEGF were highly elevated both in mice and in cultured RPE cells. Treatment with the antioxidant compound N-acetyl-cysteine (NAC) rescued the severity of CNV in diabetic mice. NAC also inhibited the overexpression of p-STAT3 and VEGF in CNV and in RPE cells. The JAK-2/STAT3 pathway inhibitor AG490 blocked VEGF expression but had no effect on the production of ROS in vitro. These results suggest that hyperglycaemia promotes the development of CNV by inducing oxidative stress, which in turn activates STAT3 signalling in RPE cells. Antioxidant supplementation helped attenuate the development of CNV. Thus, our results reveal a potential strategy for the treatment and prevention of diseases involving CNV.
C1 [Li, Xia; Cai, Yan; Wang, Yu-Sheng; Shi, Yuan-Yuan; Wang, Hai-Yan; Ye, Zi] Fourth Mil Med Univ, Xijing Hosp, Dept Ophthalmol, Xian 710032, Shaanxi Provinc, Peoples R China.
   [Yao, Li-Bo; Zhang, Jian] Fourth Mil Med Univ, Dept Biochem & Mol Biol, State Key Lab Canc Biol, Xian 710032, Shaanxi Provinc, Peoples R China.
   [Hou, Wei] Fourth Mil Med Univ, Xijing Hosp, Dept Orthoped, Xian 710032, Shaanxi Provinc, Peoples R China.
   [Xu, Chun-Sheng] Fourth Mil Med Univ, Xijing Hosp, Dept Gastrointestinal Surg, State Key Lab Canc Biol, Xian 710032, Shaanxi Provinc, Peoples R China.
C3 Air Force Military Medical University; Air Force Military Medical
   University; Air Force Military Medical University; Air Force Military
   Medical University
RP Wang, YS (通讯作者)，Fourth Mil Med Univ, Xijing Hosp, Dept Ophthalmol, Xian 710032, Shaanxi Provinc, Peoples R China.
EM wangys003@126.com; biozhangj@yahoo.com.cn
FU National Natural Science Foundation of China [30872818, 81070748];
   National Basic Research Program of China (973 Program) [2011CB510200];
   Alexander Von Humboldt Foundation in Germany [V8151/02085]
FX This work was supported by grants from the National Natural Science
   Foundation of China (No. 30872818, 81070748) and National Basic Research
   Program of China (973 Program/No. 2011CB510200). The project was
   sponsored partly by the equipment donation from the Alexander Von
   Humboldt Foundation in Germany (to Y.S.W., V8151/02085). The funders had
   no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
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NR 49
TC 42
Z9 44
U1 1
U2 19
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 19
PY 2012
VL 7
IS 10
AR e47600
DI 10.1371/journal.pone.0047600
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 023QT
UT WOS:000310050200034
PM 23094067
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Schmucker, C
   Ehlken, C
   Agostini, HT
   Antes, G
   Ruecker, G
   Lelgemann, M
   Loke, YK
AF Schmucker, Christine
   Ehlken, Christoph
   Agostini, Hansjuergen T.
   Antes, Gerd
   Ruecker, Gerta
   Lelgemann, Monika
   Loke, Yoon K.
TI A Safety Review and Meta-Analyses of Bevacizumab and Ranibizumab:
   Off-Label versus Goldstandard
SO PLOS ONE
LA English
DT Review
ID RANDOMIZED CLINICAL-TRIAL; VERTEPORFIN PHOTODYNAMIC THERAPY;
   VISION-RELATED FUNCTION; MACULAR DEGENERATION; INTRAVITREAL BEVACIZUMAB;
   SUBGROUP ANALYSIS; CANCER-PATIENTS; AVASTIN; PHARMACOKINETICS;
   TRIAMCINOLONE
AB Background: We set out a systemic review to evaluate whether off-label bevacizumab is as safe as licensed ranibizumab, and whether bevacizumab can be justifiably offered to patients as a treatment for age-related macular degeneration with robust evidence of no differential risk.
   Methods and Findings: Medline, Embase and the Cochrane Library were searched with no limitations of language and year of publication. We included RCTs with a minimum follow-up of one year which investigated bevacizumab or ranibizumab in direct comparison or against any other control group (indirect comparison). Direct comparison (3 trials, 1333 patients): The one year data show a significantly higher rate of ocular adverse effects (AE) with bevacizumab compared to ranibizumab (RR = 2.8; 95% CI 1.2-6.5). The proportion of patients with serious infections and gastrointestinal disorders was also higher with bevacizumab than with ranibizumab (RR = 1.3; 95% CI 1.0-1.7). Arterial thromboembolic events were equally distributed among the groups. Indirect comparison: Ranibizumab versus any control (5 trials, 4054 patients): The two year results of three landmark trials showed that while absolute rates of serious ocular AE were low (<= 2.1%), relative harm was significantly raised (RR = 3.1; 95% CI 1.1-8.9). A significant increase in nonocular haemorrhage was also observed with ranibizumab (RR = 1.7; 95% CI 1.1-2.7). Bevacizumab versus any control (3 trials, 244 patients): We were unable to judge the safety profile of bevacizumab due to the poor quality of AE monitoring and reporting in the trials.
   Conclusions: Evidence from head-to-head trials raises concern about an increased risk of ocular and multiple systemic AE with bevacizumab. Therefore, clinicians and patients should continue to carefully weight up the benefits and harms when choosing between the two treatment options. We also emphasize the need for studies that are powered not just for efficacy, but for defined safety outcomes based on the signals detected in this systematic review.
C1 [Schmucker, Christine; Antes, Gerd] Univ Med Ctr Freiburg, Dept Med Biometry & Stat, Inst Med Biometry & Med Informat, German Cochrane Inst, Freiburg, Germany.
   [Ehlken, Christoph; Agostini, Hansjuergen T.] Univ Med Ctr Freiburg, Univ Eye Hosp, Freiburg, Germany.
   [Loke, Yoon K.] Univ E Anglia, Sch Med, Norwich NR4 7TJ, Norfolk, England.
   [Lelgemann, Monika] German Hlth Insurance Funds, Med Advisory Serv, Essen, Germany.
C3 University of Freiburg; University of Freiburg; University of East
   Anglia
RP Schmucker, C (通讯作者)，Univ Med Ctr Freiburg, Dept Med Biometry & Stat, Inst Med Biometry & Med Informat, German Cochrane Inst, Freiburg, Germany.
EM schmucker@cochrane.de
RI Rücker, Gerta/B-2965-2009
OI Rücker, Gerta/0000-0002-2192-2560; Schmucker,
   Christine/0000-0002-1188-3158
FU German Federal Ministry of Education and Research [01KG1020]
FX This research was supported by a grant from the German Federal Ministry
   of Education and Research (Grant number: 01KG1020,
   http://www.gesundheitsforschung-bmbf.de/de/4312.php). The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.
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NR 43
TC 92
Z9 96
U1 0
U2 26
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 3
PY 2012
VL 7
IS 8
AR e42701
DI 10.1371/journal.pone.0042701
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 985QT
UT WOS:000307284100160
PM 22880086
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Kwon, KJ
   Kim, HJ
   Shin, CY
   Han, SH
AF Kwon, Kyoung Ja
   Kim, Hee-Jin
   Shin, Chan Young
   Han, Seol-Heui
TI Melatonin Potentiates the Neuroprotective Properties of Resveratrol
   Against Beta-Amyloid-Induced Neurodegeneration by Modulating
   AMP-Activated Protein Kinase Pathways
SO JOURNAL OF CLINICAL NEUROLOGY
LA English
DT Article
DE melatonin; resveratrol; neuroprotection; reactive oxygen species;
   glycogen synthase kinase 3 beta; AMP-activated protein kinase
ID HIPPOCAMPAL SLICE CULTURES; ALZHEIMERS-DISEASE; ERK1/2 ACTIVATION;
   IN-VIVO; MICE; INHIBITION; EXPRESSION; PREVENTION; INCREASES; THERAPY
AB Background and Purpose Recent studies have demonstrated that resveratrol (RSV) reduces the incidence of age-related macular degeneration, Alzheimer's disease (AD), and stroke, while melatonin (MEL) supplementation reduces the progression of the cognitive impairment in AD patients. The purpose of this investigation was to assess whether the co-administration of MEL and RSV exerts synergistic effects on their neuroprotective properties against beta-amyloid (A beta)-induced neuronal death.
   Methods The neuroprotective effects of co-treatment with MEL and RSV on A beta 1-42 -induced cell death, was measured by MTT reduction assay. A beta 1-42 caused an increase in intracellular levels of reactive oxygen species (ROS), as assessed by H-2-DCF-DA dye, and a reduction of total glutathione (GSH) levels and mitochondrial membrane potential, as assessed using monochlorobimane and rhodamine 123 fluorescence, respectively. Western blotting was used to investigate the intracellular signaling mechanism involved in these synergic effects.
   Results We treated a murine HT22 hippocampal cell line with MEL or RSV alone or with both simultaneously. MEL and RSV alone significantly attenuated ROS production, mitochondrial membrane-potential disruption and the neurotoxicity induced by A beta 1-42. They also restored the A beta 1-42-induced depletion of GSH, back to within its normal range and prevented the A beta 1-42-induced activation of glycogen synthase kinase 3 beta (GSK3 beta). However, co-treatment with MEL and RSV did not exert any significant synergistic effects on either the recovery of the A beta 1-42-induced depletion of GSH or on the inhibition of A beta 1-42-induced GSK3 beta activation. A beta 1-42 treatment increased AMP-activated protein kinase (AMPK) activity, which is associated with subsequent neuronal death. We demonstrated that MEL and RSV treatment inhibited the phosphorylation of AMPK.
   Conclusions Together, our results suggest that co-administration of MEL and RSV acts as an effective treatment for AD by attenuating A beta 1-42-induced oxidative stress and the AMPK-dependent pathway. J Clin Neurol 2010;6:127-137
C1 [Kwon, Kyoung Ja; Han, Seol-Heui] Konkuk Univ, Sch Med, Inst Biomed Sci & Technol, Ctr Geriatr Neurosci Res,Dept Neurol, Seoul 143701, South Korea.
   [Shin, Chan Young] Konkuk Univ, Sch Med, Inst Biomed Sci & Technol, Ctr Geriatr Neurosci Res,Dept Pharmacol, Seoul 143701, South Korea.
   [Kim, Hee-Jin] Hanyang Univ, Coll Med, Dept Neurol, Seoul 133791, South Korea.
C3 Konkuk University; Konkuk University Medical Center; Konkuk University;
   Konkuk University Medical Center; Hanyang University
RP Han, SH (通讯作者)，Konkuk Univ, Sch Med, Inst Biomed Sci & Technol, Ctr Geriatr Neurosci Res,Dept Neurol, 1 Hwayang Dong, Seoul 143701, South Korea.
EM alzdoc@kuh.ac.kr
FU Ministry of Education, Science and Technology [R33-2008-000-10090-0]
FX This work was supported by WCU (World Class University) program through
   the National Research Foundation of Korea funded by the Ministry of
   Education, Science and Technology (R33-2008-000-10090-0).
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NR 32
TC 73
Z9 79
U1 7
U2 41
PU KOREAN NEUROLOGICAL ASSOC
PI SEOUL
PA 1111 DAEIL BLD, 43 INSA-DONG, JONGNO-GU, SEOUL, 110-741, SOUTH KOREA
SN 1738-6586
EI 2005-5013
J9 J CLIN NEUROL
JI J. Clin. Neurol.
PD SEP
PY 2010
VL 6
IS 3
BP 127
EP 137
DI 10.3988/jcn.2010.6.3.127
PG 11
WC Clinical Neurology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 655PI
UT WOS:000282261500003
PM 20944813
OA Green Published
DA 2022-11-30
ER

PT J
AU Lin, JC
   Chie, WC
AF Lin, Jen-Chieh
   Chie, Wei-Chu
TI Psychometric validation of the Taiwan Chinese version of the 25-Item
   National Eye Institute Visual Functioning Questionnaire
SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE
LA English
DT Article
DE NEI-VFQ 25; quality of life; validation of questionnaire
ID QUALITY-OF-LIFE; POPULATION; IMPACT
AB Objectives
   To evaluate the reliability and construct validity of a Taiwan Chinese version of the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ 25) in patients with visual impairment.
   Methods
   The NEI-VFQ 25 was translated and adapted into the Taiwan Chinese version. In total, 222 patients responded to the questionnaire. To examine reliability, Cronbach's alpha for each subscale was used as an index of internal consistency. Test-retest reliability was evaluated with intraclass correlation coefficients. Regarding construct validity, both convergent and discriminant validities were calculated by means of multi-trait analysis. Clinical validity was examined by correlation of clinical measurements and subscale scores and known-groups comparison. Finally, correlation between different subscales was examined to evaluate hypothetical relationship between subscales.
   Results
   Five patient groups were studied, each including participants with a single cause of visual impairment. Group 1 consisted of 53 cataract patients; group 2 included 51 subjects with glaucoma; group 3 included 36 subjects with age-related macular degeneration (ARMD); and group 4 included 48 subjects with diabetic retinopathy. Thirty-four individuals with uncorrected refractive error comprised the control group. NEI-VFQ scores (mean +/- SD) for the cataract, glaucoma, ARMD, diabetic retinopathy and control groups were: 73.5 +/- 17.1, 69.2 +/- 20.4, 62.3 +/- 23.7, 63.7 +/- 20.8 and 80.7 +/- 12.0, respectively. Item analysis revealed moderate data skewing. Cronbach's alpha coefficients of subscales ranged from 0.956 (mental health) to 0.964 (near activities). Intraclass correlation coefficients ranged from 0.41 (driving) to 0.846 (distance activities). All items passed the convergent and discriminant validity tests. Moderate correlations were detected between visual acuity and the 'general vision', 'distance activities' and 'near activities' subscales. Significant correlations were detected between visual field deficits and the vision associated subscales.
   Conclusion
   This study revealed that the Taiwan Chinese version of the NEI-VFQ 25 is a valid and reliable instrument to measure vision-related quality of life in patients with visual impairment.
C1 [Lin, Jen-Chieh] Taipei City Hosp, Dept Ophthalmol, Heping Branch, Taipei 10065, Taiwan.
   [Lin, Jen-Chieh; Chie, Wei-Chu] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Prevent Med, Taipei 10764, Taiwan.
C3 Taipei City Hospital; National Taiwan University
RP Lin, JC (通讯作者)，Taipei City Hosp, Dept Ophthalmol, Heping Branch, 33,Sec 2,Chung Hwa Rd, Taipei 10065, Taiwan.
EM jclin54@yahoo.com.tw
OI Chie, Wei-Chu/0000-0001-5584-6554
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NR 30
TC 32
Z9 33
U1 0
U2 14
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1356-1294
EI 1365-2753
J9 J EVAL CLIN PRACT
JI J. Eval. Clin. Pract.
PD JUN
PY 2010
VL 16
IS 3
BP 619
EP 626
DI 10.1111/j.1365-2753.2009.01253.x
PG 8
WC Health Care Sciences & Services; Medical Informatics; Medicine, General
   & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services; Medical Informatics; General & Internal
   Medicine
GA 601QM
UT WOS:000278077900035
PM 19712207
DA 2022-11-30
ER

PT J
AU Shi, X
   Semkova, I
   Muther, PS
   Dell, S
   Kociok, N
   Joussen, AM
AF Shi, Xuan
   Semkova, Irina
   Muether, Philipp S.
   Dell, Susanne
   Kociok, Norbert
   Joussen, Antonia M.
TI Inhibition of TNF-alpha reduces laser-induced choroidal
   neovascularization
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE choroidal neovascularization; TNF-alpha; leakage
ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL GROWTH-FACTOR; ANGIOGENESIS;
   EXPRESSION; LYMPHOTOXIN; MACROPHAGES; RECEPTORS; UVEITIS; CELLS
AB To investigate the role of the TNF-alpha in the development of laser-induced choroidal neovascularization (CNV) in a mouse model. Four separate laser burns were applied to induce ruptures of Bruch's membrane and subsequent choroidal neovascularization in C57BL/6J mice. TNF-alpha protein expression was serniquantitatively assessed by Western blot analysis of the choroidal and RPE layer from mice with or without laser treatment. To investigate the effect of TNF-a inhibition on CNV formation, animals were treated for 7 days via intraperitonealy implanted osmotic pumps either 3 days before or after laser injury with recombinant TNF receptor P75 (etanercept), a chimeric monoclonal antibody (infliximab), or a purified rat anti-mouse/rat TNF monoclonal antibody (TNF-mAb), respectively. Fluorescein angiography, flat-mount preparations, and histopathology were performed at day 7, 10, or 14 after laser treatment. Western blotting demonstrated that TNF-alpha expression was 4.57-fold higher in the choroid and RPE one week after laser injury compared to control mice without laser. When evaluated one and two weeks after laser injury, etanercept and infliximab given from the 3rd day before laser-damage significantly reduced CNV size and pathological fluorescein leakage compared to the control group after laser treatment only. The inhibitory effect of the monoclonal TNF-alpha antibody on CNV formation was evident two weeks after photocoagulation but not after one week. Only etanercept administered 3 days after laser injury still reduced significantly the development of CNV lesions. Histopathology confirmed that CNV lesions in treated mice were smaller in size compared to the control animals without TNF inhibitor treatment. In conclusion, anti-TNF-alpha. treatment with different inhibitors reduces both the size and the leakage of laser-induced CNV. These results suggest the involvement of TNF-alpha in the development of laser-induced CNV and its potential use as a therapeutic agent in the age-related macular degeneration. (c) 2006 Elsevier Ltd. All rights reserved.
C1 Univ Dusseldorf, Dept Ophthalmol, D-40225 Dusseldorf, Germany.
   Univ Cologne, CMMC, D-5000 Cologne 41, Germany.
   Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100871, Peoples R China.
C3 Heinrich Heine University Dusseldorf; University of Cologne; Peking
   University
RP Joussen, AM (通讯作者)，Univ Dusseldorf, Dept Ophthalmol, Moorenstr 5, D-40225 Dusseldorf, Germany.
EM joussena@googlemail.com
RI Joussen, Antonia/AAA-6901-2022
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NR 35
TC 103
Z9 107
U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD DEC
PY 2006
VL 83
IS 6
BP 1325
EP 1334
DI 10.1016/j.exer.2006.07.007
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 109IF
UT WOS:000242300700004
PM 16959248
DA 2022-11-30
ER

PT J
AU Jonas, JB
   Kreissig, I
   Budde, WM
   Degenring, RF
AF Jonas, JB
   Kreissig, I
   Budde, WM
   Degenring, RF
TI Cataract surgery combined with intravitreal injection of triamcinolone
   acetonide
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; cataract surgery; diabetic macular
   edema; phacoemulsification; triamcinolone acetonide; intraocular
   pressure
ID CYSTOID MACULAR EDEMA; RETINAL VEIN OCCLUSION; CHOROIDAL
   NEOVASCULARIZATION; CRYSTALLINE CORTISONE; INTRAOCULAR-PRESSURE;
   ADJUNCTIVE TREATMENT; NONINFECTIOUS ENDOPHTHALMITIS; RAT MODEL;
   DEGENERATION; TELANGIECTASIS
AB PURPOSE. To evaluate whether the addition of cataract surgery to an intravitreal injection of triamcinolone acetonide markedly increases frequency and spectrum of complications.
   METHODS. The comparative nonrandomized clinical interventional investigation included a study group of 60 eyes (56 patients) undergoing cataract surgery and additionally receiving an intravitreal injection of about 20 mg of triamcinolone acetonide and a triamcinolone control group of 290 eyes (262 patients) that consecutively received an intravitreal injection of about 20 mg triamcinolone acetonide without cataract surgery. Reasons for intravitreal injection of triamcinolone acetonide were exudative age-related macular degeneration (n=228; 65%), diffuse diabetic macular edema (n=94; 27%), central retinal vein occlusion (n=1 7; 5%), and branch retinal vein occlusion (n=1 1; 3%). Mean follow-up was 8.6 +/- 6.8 months. A second control group included 1068 patients (1068 eyes) who consecutively underwent routine cataract surgery without intravitreal injection.
   RESULTS. Study group and triamcinolone control group did not vary significantly in best visual acuity during follow-up (p=0.08), final visual acuity at the end of follow-up (p=0.30), maximal intraocular pressure during follow-up (p=0.99), frequency of an intraocular pressure higher than 21 mmHg (p=0.66), and intraocular pressure at the end of follow-up (p=0.06). Postoperative infectious endophthalmitis, wound leakage or other corneal wound healing problems, persisting corneal endothelial decompensation, rhegmatogenous retinal detachment, marked postoperative pain, or a clinically significant decentration of the intraocular lens were not observed. Study group and the non-triamcinolone control group did not vary significantly in the rate of posterior lens capsule rupture (p=0.11), postoperative infectious endophthalmitis, and persisting postoperative corneal endothelial decompensation.
   CONCLUSIONS. The addition of cataract surgery to an intravitreal injection of triamcinolone acetonide may not markedly increase amount and frequency of side effects and complications of intravitreal triamcinolone acetonide. No safe conclusions can be reached regarding differences in frequency of postoperative infectious endophthalmitis.
C1 Univ Heidelberg, Fac Clin Med Mannheim, Dept Ophthalmol, D-6900 Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg
RP Jonas, JB (通讯作者)，Univ Augenklin, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany.
EM Jost.Jonas@ma.augen.uni-heidelberg.de
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NR 53
TC 10
Z9 10
U1 0
U2 1
PU WICHTIG EDITORE
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 1120-6721
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD MAY-JUN
PY 2005
VL 15
IS 3
BP 329
EP 335
DI 10.1177/112067210501500303
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 935WE
UT WOS:000229813300003
PM 15945000
DA 2022-11-30
ER

PT J
AU Richert, E
   Papenkort, J
   Klettner, A
   Tode, J
   Koinzer, S
   Brinkmann, R
   Fink, C
   Roeder, T
   Lucius, R
   Roider, J
AF Richert, Elisabeth
   Papenkort, Julia
   Klettner, Alexa
   Tode, Jan
   Koinzer, Stefan
   Brinkmann, Ralf
   Fink, Christine
   Roeder, Thomas
   Lucius, Ralph
   Roider, Johann
TI Response of Retinal Pigment Epithelium (RPE)-Choroid Explants to Thermal
   Stimulation Therapy of the RPE (TSR)
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE age-related macular degeneration; thermal stimulation therapy of the
   retinal pigment epithelium; matrix metalloproteases; pigment epithelium
   derived factor; retinal pigment epithelium; vascular endothelial growth
   factor; transforming growth factor-beta
ID ENDOTHELIAL GROWTH-FACTOR; HUMAN BRUCHS MEMBRANE; MACULAR DEGENERATION;
   FACTOR-BETA; METALLOPROTEINASE ACTIVITY; IN-VITRO; AGE; LASER; DRUSEN;
   MECHANISMS
AB Background and Objectives The thermal stimulation therapy of the retinal pigment epithelium (TSR) is a sublethal laser technique for thermal stimulation of the retinal pigment epithelium (RPE)-Bruch's membrane (BrM)-complex. The aim of this study was to investigate the influence of TSR on the release of age-related macular degeneration (AMD)-relevant cell mediators. Study Design/Materials and Methods Porcine RPE-BrM-choroid explants were irradiated with a 532 nm continuous wave laser using different spot sizes (100-300 mu m, duration 100 milliseconds, 15-100 mW). Cell death was investigated by calcein staining. Explants were treated with grids of sublethal spots and cultivated in modified Ussing chambers. The effect on matrix metalloproteinase-2 (MMP-2) and -9 was investigated by zymography and quantitative reverse transcription polymerase chain reaction. Secretion of vascular endothelial growth factor (VEGF), pigment epithelium derived factor (PEDF), and transforming growth factor-beta (TGF-beta) was analyzed by enzyme-linked immunosorbent assay and expression of HSP70 was examined by western blot. Integrity of the RPE/BrM-complex was analyzed by scanning electron microscopy. Results Laser powers of 15 mW (100 mu m) and 45 mW (300 mu m) did not induce RPE cell death. The integrity of the RPE/BrM-complex was not impaired after TSR. After TSR with 300 mu m spot size, we observed a significant increase of active MMP-2 in the basal compartments. The content of PEDF significantly increased in treated explants in both compartments with 100 and 300 mu m spot sizes. VEGF and TGF-beta secretion was not triggered by TSR. Conclusions TSR represents a possible RPE stimulating treatment for dry AMD. TSR increases the basal release of active MMP-2, which might reverse age-related thickening of BrM. VEGF secretion was not triggered by TSR while anti-angiogenic PEDF was increased, indicating an induction of an anti-angiogenic and neuroprotective environment. Lasers Surg. Med. (c) 2020 Wiley Periodicals LLC
C1 [Richert, Elisabeth; Papenkort, Julia; Klettner, Alexa; Tode, Jan; Koinzer, Stefan; Roider, Johann] Christian Albrechts Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller St 3,House 3B, D-24105 Kiel, Germany.
   [Brinkmann, Ralf] Med Laser Ctr Lubeck, Peter Monnik Weg 4, D-23562 Lubeck, Germany.
   [Fink, Christine; Roeder, Thomas] Christian Albrechts Univ Kiel, Zool Inst, Mol Physiol, Bot Garten 1-9, D-24118 Kiel, Germany.
   [Lucius, Ralph] Christian Albrechts Univ Kiel, Inst Anat, Olshausenstr, D-24118 Kiel, Germany.
C3 University of Kiel; Schleswig Holstein University Hospital; University
   of Kiel; University of Kiel
RP Richert, E (通讯作者)，Christian Albrechts Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller St 3,House 3B, D-24105 Kiel, Germany.
EM elisabeth.richert@web.de
RI Brinkmann, Ralf/HDL-7611-2022; Roeder, Thomas/B-9016-2011; Fink,
   Christine/ABF-7102-2021; Brinkmann, Ralf/E-6701-2012
OI Roeder, Thomas/0000-0002-3489-3834; Brinkmann, Ralf/0000-0002-0445-8102;
   Klettner, Alexa/0000-0002-2709-1059; Fink, Christine/0000-0003-0083-2168
FU Federal Ministry of Education and Research [BMBF] [13GW0043D]
FX The authors would like to thank Andrea Hethke, Mandy Gotz, Kathinka
   Winter and Frank Lichte for their excellent technical assistance. This
   study was supported by the Federal Ministry of Education and Research
   [BMBF; grant number: 13GW0043D]. Data from this study has been presented
   at the ARVO meeting 2016 in Seattle, Washington, USA.
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NR 67
TC 3
Z9 3
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0196-8092
EI 1096-9101
J9 LASER SURG MED
JI Lasers Surg. Med.
PD MAR
PY 2021
VL 53
IS 3
BP 359
EP 369
DI 10.1002/lsm.23288
EA JUN 2020
PG 11
WC Dermatology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Dermatology; Surgery
GA QZ2AJ
UT WOS:000541414600001
PM 32567146
DA 2022-11-30
ER

PT J
AU Desmettre, T
AF Desmettre, T.
TI Geographic Atrophy and micronutritional supplements: A complex
   relationship
SO JOURNAL FRANCAIS D OPHTALMOLOGIE
LA English
DT Article
DE Age-Related Macular Degeneration; Geographic Atrophy; Micronutrition;
   AREDS
ID MACULAR DEGENERATION; PROGRESSION; OMEGA-3-FATTY-ACIDS
AB In 2019, the Age-Related Eye Disease Study (AREDS) remains the basis for micronutritional supplement guidelines aiming to stow the progression of Age-Related Macular Degeneration (AMD) and reduce the risk of neovascularization. However, for Geographic Atrophy (GA) patients specifically, there seem to be more arguments for prescribing micronutritional supplements for the prevention of neovascular complications than to slow the progression of the atrophy. The AREDS report 8 showed a significant decrease in AMD progression over a five- year follow-up associated with a formulation containing antioxidants and zinc. It is noteworthy that the protective effect that was demonstrated was mainly related to the risk of a neovascularization and that the AREDS did not really demonstrate a protective effect that would slow the progression of GA. The 2013 AREDS II results have led to a change in the AREDS formulation. Nevertheless, the replacement of beta-carotene by lutein and zeaxanthine and the addition of Omega-3 did not add any further evidence for a protective effect on GA. Furthermore, the AREDS study used color photographs rather than fundus autofluorescence or OCT to assess the presence or the evolution of patches of atrophy. Over the last 10 years, it has been shown that OCT is far more accurate than color photographs to measure the size of the atrophic areas and to evaluate the extent of alterations in the chorioretinal layers. While tack of evidence of a protective effect of the AREDS formulation for GA is not a proof of the absence of effect, many publications seem to have taken the results of the AREDS in such a global way that the lack of evidence concerning GA seems to have been ignored. Micronutrition supplements are welt prescribed for AMD patients, and the key factor for adherence is explanation to the patient. So far, it appears worth explaining to GA patients that prescription of the AREDS formulation is mainly aimed at reducing the risk of neovascularization. (C) 2019 Elsevier Masson SAS. All rights reserved.
C1 [Desmettre, T.] Ctr Retine Med, 187 Rue Menin, F-59520 Marquette Lez Lille, France.
   [Desmettre, T.] Queen Anne St Med Ctr, 18-22 Queen Anne St, London W1G 8HU, England.
RP Desmettre, T (通讯作者)，Ctr Retine Med, 187 Rue Menin, F-59520 Marquette Lez Lille, France.
EM thomas@desmettre.org
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NR 16
TC 0
Z9 0
U1 0
U2 4
PU MASSON EDITEUR
PI MOULINEAUX CEDEX 9
PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE
SN 0181-5512
EI 1773-0597
J9 J FR OPHTALMOL
JI J. Fr. Ophthamol.
PD DEC
PY 2019
VL 42
IS 10
BP 1111
EP 1115
DI 10.1016/j.jfo.2019.07.003
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JR5RY
UT WOS:000499683200022
PM 31722806
DA 2022-11-30
ER

PT J
AU Kovac, B
   Vukosavljevic, M
   Kovac, JD
   Resan, M
   Trajkovic, G
   Jankovic, J
   Smiljanic, M
   Grgurevic, A
AF Kovac, Bojan
   Vukosavljevic, Miroslav
   Kovac, Jelena Djokic
   Resan, Mirko
   Trajkovic, Goran
   Jankovic, Janko
   Smiljanic, Milena
   Grgurevic, Anita
TI Validation and cross-cultural adaptation of the National Eye Institute
   Visual Function Questionnaire (NEI VFQ-25) in Serbian patients
SO HEALTH AND QUALITY OF LIFE OUTCOMES
LA English
DT Article
ID QUALITY-OF-LIFE; CATARACT-SURGERY OUTCOMES; PSYCHOMETRIC PROPERTIES;
   RASCH ANALYSIS; VERSION; VISION; VALIDITY; IMPACT; POPULATION;
   TRANSLATION
AB Purpose: To test the validity and reliability of the Serbian version of the interviewer-administered format of the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25).
   Methods: The Serbian version of NEI VFQ-25 was translated in accordance with standard methods that have been adopted internationally. In order to assess the reliability and validity of the translated NEI VFQ-25, we used a sample of 105 patients with four different chronic ocular diseases. Cronbach's alpha coefficient was used to assess internal consistency for each subscale. To assess test-retest reliability, intraclass correlation coefficients were used. The test-retest data were obtained from clinically stable patients with age-related cataracts, in surveys performed 2 weeks apart. Rasch analysis was also applied as a modern methods of psychometric assessment of the questionnaire.
   Results: Four groups of patients were studied and the most prevalent were patients with cataract 40 (38.1 %), followed by diabetic retinopathy 31 (29.5 %), age related macular degeneration 22 (21.0 %) and glaucoma 12 (11.4 %). The overall index score on the NEI VFQ-25 ranged from 65.3 to 67.8 with a mean of 67.4 +/- 15.0. Cronbach's alpha coefficient (index of internal consistency reliability) ranged from 0.643 to 0.889 for the subscales. Evaluation of the validity of the Serbian version of NEI VFQ-25 is presented in the multi-trait-multi-method matrix and all items passed the convergent and discriminant validity tests. Rasch analysis showed a good measurement precision, but also demonstrated misfitting items and multidimensionality of the questionnaire.
   Conclusion: Although traditional validation method indicates that the Serbian version of NEI VFQ-25 is a valid and reliable instrument for the assessment of vision specific QoL in Serbian populations aged 40 years or older, Rasch analysis revealed a substantial weakness of the questionnaire that should be taken into consideration when interpreting the results.
C1 [Kovac, Bojan; Vukosavljevic, Miroslav; Resan, Mirko; Smiljanic, Milena] Univ Def, Fac Med, Clin Ophthalmol, Mil Med Acad, Belgrade, Serbia.
   [Kovac, Jelena Djokic] Univ Belgrade, Clin Ctr Serbia, Fac Med, Belgrade 102, Serbia.
   [Trajkovic, Goran] Univ Belgrade, Inst Med Stat & Informat, Fac Med, Belgrade 102, Serbia.
   [Jankovic, Janko] Univ Belgrade, Inst Social Med, Fac Med, Belgrade 102, Serbia.
   [Grgurevic, Anita] Univ Belgrade, Inst Epidemiol, Fac Med, Belgrade 102, Serbia.
C3 University of Belgrade; Clinical Centre of Serbia; University of
   Belgrade; University of Belgrade; University of Belgrade; University of
   Belgrade
RP Grgurevic, A (通讯作者)，Univ Belgrade, Inst Epidemiol, Fac Med, Visegradska 26a,POB 20 11129, Belgrade 102, Serbia.
EM anita.grgurevic@gmail.com
OI Jankovic, Janko/0000-0002-2387-6596
FU Ministry of Education, Science and Technological Development of the
   Republic of Serbia [175042, 175087]
FX This investigation was supported by the Ministry of Education, Science
   and Technological Development of the Republic of Serbia (Grant No.
   175042 and No. 175087).
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NR 37
TC 27
Z9 29
U1 1
U2 28
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-7525
J9 HEALTH QUAL LIFE OUT
JI Health Qual. Life Outcomes
PD SEP 15
PY 2015
VL 13
AR 142
DI 10.1186/s12955-015-0330-5
PG 13
WC Health Care Sciences & Services; Health Policy & Services
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Health Care Sciences & Services
GA CR5AV
UT WOS:000361352100001
PM 26370558
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Finger, RP
   Wu, ZC
   Luu, CD
   Kearney, F
   Ayton, LN
   Lucci, LM
   Hubbard, WC
   Hageman, JL
   Hageman, GS
   Guymer, RH
AF Finger, Robert P.
   Wu, Zhichao
   Luu, Chi D.
   Kearney, Frances
   Ayton, Lauren N.
   Lucci, Lucia M.
   Hubbard, William C.
   Hageman, Jill L.
   Hageman, Gregory S.
   Guymer, Robyn H.
TI Reticular Pseudodrusen A Risk Factor for Geographic Atrophy in Fellow
   Eyes of Individuals with Unilateral Choroidal Neovascularization
SO OPHTHALMOLOGY
LA English
DT Article
ID PREVALENCE
AB Purpose: To determine whether reticular pseudodrusen (RPD) confer an increased risk of progression to latestage age-related macular degeneration (AMD) in fellow eyes of those recently diagnosed with unilateral choroidal neovascularization (CNV).
   Design: Retrospective study.
   Participants: Two hundred consecutive participants with CNV secondary to AMD in 1 eye and no signs of late-stage AMD in the fellow eye.
   Methods: Clinical examination and comprehensive retinal imaging, including spectral-domain optical coherence tomography, near-infrared reflectance (NIR), and color fundus photography, at baseline and every follow-up visit.
   Main Outcome Measures: Incidence of geographic atrophy (GA) and CNV in the fellow eye.
   Results: Mean age +/- standard deviation was 77 +/- 7 years, and 61% of the cohort were female. Fifty-eight percent (n = 116) had RPD, 68% had drusen of 125 mm or more, 36% had pigmentary changes, 10% had both drusen of 125 mu m or more and pigmentary changes, and 17% had only RPD in their fellow eyes. After a mean follow-up of 2.3 years, CNV developed in 36% of patients and GA developed in 14% of patients. Those with RPD demonstrated late-stage AMD (61% vs. 33.4%; P< 0.001) and GA (22.4% with RPD vs. 2.4% without RPD; P< 0.001) more often. The presence of reticular pseudodrusen was an independent risk factor for the development of GA (hazard ratio [HR], 4.93; P = 0.042), but not for CNV (HR, 1.19; P = 0.500), at least within the follow-up of this study. Both drusen of 125 mu m or more and pigmentary changes at baseline were significant risk factors for the development of CNV and GA (HR, 1.96-11.73; P <= 0.020).
   Conclusions: Reticular pseudodrusen seem to confer an increased risk of progression to GA, in addition to drusen and pigmentary changes. The presence of RPD needs to be taken into account when discussing a patient's prognosis and planning management. (C) 2014 by the American Academy of Ophthalmology.
C1 [Finger, Robert P.; Wu, Zhichao; Luu, Chi D.; Kearney, Frances; Ayton, Lauren N.; Guymer, Robyn H.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic 3010, Australia.
   [Lucci, Lucia M.; Hubbard, William C.; Hageman, Jill L.; Hageman, Gregory S.] Univ Utah, Dept Ophthalmol & Visual Sci, John A Moran Eye Ctr, Salt Lake City, UT USA.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; Utah System of Higher Education; University of
   Utah
RP Finger, RP (通讯作者)，Ctr Eye Res Australia, Macular Res Unit, Level 1,32 Gisborne St, East Melbourne, Vic 3002, Australia.
EM robert.finger@unimelb.edu.au
RI Ayton, Lauren/AAV-2977-2021
OI Ayton, Lauren/0000-0001-9907-084X; Finger, Robert P/0000-0003-4253-7597;
   Luu, Chi/0000-0002-7604-7097; Guymer, Robyn/0000-0002-9441-4356
FU German Research Council [DFG FI 1540/5-1]; Perpetual Foundation
   Australia; Novartis Australia; Bayer Australia; National Health and
   Medical Research Council Australia [590205, 1008979, 529905]; Centre for
   Clinical Research Excellence [529923]; Macular Degeneration Foundation
   Australia; BrightFocus Foundation, Clarksburg, MD; National Institutes
   of Health, Bethesda, Maryland [R24 EY017404]; American Macular
   Degeneration Foundation, Inc, Northampton, MA; Helen K. and Arthur E.
   Johnson Foundation, Denver, CO; Willard L. Eccles Charitable Foundation,
   Salt Lake City, UT; Research to Prevent Blindness, Inc., New York, New
   York; NATIONAL EYE INSTITUTE [P30EY014800, R24EY017404] Funding Source:
   NIH RePORTER
FX Supported by the German Research Council (grant no.: DFG FI 1540/5-1
   [R.P.F.]); the Perpetual Foundation Australia; Novartis Australia; Bayer
   Australia; the National Health and Medical Research Council Australia
   (grant nos.: 590205 and 1008979; practitioner fellowship no.: 529905
   [R.H.G.]; and Centre for Clinical Research Excellence grant no.:
   529923); the Macular Degeneration Foundation Australia (R.H.G. and
   G.S.H.); the BrightFocus Foundation, Clarksburg, MD; the National
   Institutes of Health, Bethesda, Maryland (grant no.: R24 EY017404
   [G.S.H.]); the American Macular Degeneration Foundation, Inc,
   Northampton, MA; (G.S.H.); the Helen K. and Arthur E. Johnson
   Foundation, Denver, CO; (G.S.H.); the Willard L. Eccles Charitable
   Foundation, Salt Lake City, UT (G.S.H.); Sylvia E. Prahl-Brodbeck
   (G.S.H.); Sharon E. Steele-McGee; and Research to Prevent Blindness,
   Inc., New York, New York (unrestricted grant to the University of Utah
   John A. Moran Eye Center and the Department of Ophthalmology and Visual
   Sciences). The Centre for Eye Research Australia receives operational
   infrastructure support from the Victorian Government. The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.
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NR 14
TC 119
Z9 123
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUN
PY 2014
VL 121
IS 6
BP 1252
EP 1256
DI 10.1016/j.ophtha.2013.12.034
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AJ0KG
UT WOS:000337339100018
PM 24518615
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Shan, HD
   Ji, D
   Barnard, AR
   Lipinski, DM
   You, QS
   Lee, EJ
   Kamalden, TA
   Sun, XH
   MacLaren, RE
AF Shan, Haidong
   Ji, Dan
   Barnard, Alun R.
   Lipinski, Daniel M.
   You, Qisheng
   Lee, Edward J.
   Kamalden, Tengku Ain
   Sun, Xinghuai
   MacLaren, Robert E.
TI AAV-Mediated Gene Transfer of Human X-Linked Inhibitor of Apoptosis
   Protects against Oxidative Cell Death in Human RPE Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINITIS-PIGMENTOSA; CASPASE ACTIVATION; MACULAR DEGENERATION;
   NEURODEGENERATION; PHOTORECEPTORS; PROLIFERATION; MITOCHONDRIA;
   EXPRESSION; NEURONS; MODELS
AB PURPOSE. To determine whether human X-linked inhibitor of apoptosis (XIAP) enhances the survival of cultured human retinal pigment epithelial cells exposed to H(2)O(2).
   METHODS. ARPE-19 cells were exposed to H(2)O(2) to induce oxidative cell death. Intracellular reactive oxygen species (ROS) were measured using 2',7'-dichlorofluorescein diacetate. MTT assay was performed to quantify mitochondrial stress. Cell apoptosis was determined by TUNEL assay. Human XIAP was delivered with bicistronic expression of green fluorescent protein (GFP), using recombinant adeno-associated virus (AAV-XIAP-GFP). The null vector, containing identical sequences but without XIAP, was used as a control (AAV-NULL-GFP). Transduced cells underwent fluorescence-activated cell sorting. XIAP overexpression was examined by immunostaining and Western blot analysis.
   RESULTS. ARPE-19 cells exposed to 0.25 mM H(2)O(2) for 1 hour showed increased TUNEL staining compared with nonstressed cells (17 +/- 1.4 vs. 1.8 +/- 0.4 cells per 20 x field; P = 0.000006), accompanied by a significant increase in intracellular ROS (207 +/- 46% vs. 100 +/- 9.5%; P = 0.0002). The AAV-XIAP-GFP transduced cells had 11-fold higher XIAP expression than the AAV-NULL-GFP controls (1300 +/- 126% vs. 120 +/- 10%; P = 0.0006). XIAP over-expression significantly reduced the number of apoptotic cells after stress compared with the AAV-NULL-GFP controls (3.2 +/- 0.6 vs. 18 +/- 1.6 cells per 20 x field; P = 0.00003). Mitochondrial stress was reduced by AAV-XIAP-GFP, but did not reach a statistical significance (68 +/- 3.5% vs. 74 +/- 3.8%; P = 0.24).
   CONCLUSIONS. Overexpression of human XIAP protects ARPE-19 cells against H(2)O(2)-induced oxidative cell death by acting downstream on the apoptotic pathway. XIAP gene therapy using AAV may provide a means of reducing the effect of oxidative stress to RPE cells in age-related macular degeneration. (Invest Ophthalmol Vis Sci. 2011; 52:9591-9597) DOI: 10.1167/iovs.10-6850
C1 [Shan, Haidong; Ji, Dan; Barnard, Alun R.; Lipinski, Daniel M.; You, Qisheng; Kamalden, Tengku Ain; MacLaren, Robert E.] Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX3 9DU, England.
   [Shan, Haidong; Ji, Dan; Barnard, Alun R.; Lipinski, Daniel M.; You, Qisheng; Kamalden, Tengku Ain; MacLaren, Robert E.] Oxford Univ Hosp, NIHR Biomed Res Ctr, Oxford, England.
   [Lee, Edward J.; MacLaren, Robert E.] Moorfields Eye Hosp, UCL Inst Ophthalmol, NIHR Biomed Res Ctr, London, England.
   [Sun, Xinghuai] Fudan Univ, Eye & ENT Hosp, Shanghai 200433, Peoples R China.
C3 University of Oxford; University of Oxford; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   Fudan University
RP MacLaren, RE (通讯作者)，Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX3 9DU, England.
EM enquiries@eye.ox.ac.uk
RI You, Qisheng/A-3619-2014; You, Qisheng/AAG-7153-2020; KAMALDEN, TENGKU
   AIN FATHLUN TENGKU/B-9941-2010
OI You, Qisheng/0000-0003-0743-7320; You, Qisheng/0000-0003-0743-7320;
   KAMALDEN, TENGKU AIN FATHLUN TENGKU/0000-0001-9810-5334; MacLaren,
   Robert/0000-0002-3096-4682; Lipinski, Daniel/0000-0001-7828-614X
FU The Health Foundation; Special Trustees of Moorfields Eye Hospital; NIHR
   Biomedical Research Centre; Royal College of Surgeons of Edinburgh;
   Fight for Sight; Royal Blind; Scottish National Institute for the War
   Blinded; Wellcome Trust [WT 086868]; The Medical Research Council UK
   [G0601588]; National Basic Research Program of China [2007CB512204];
   China State Scholarship; China Oxford Scholarship; Henry Lester Trust;
   Eye & ENT Hospital of Fudan University; Beijing Institute of
   Ophthalmology, Beijing Tongren Hospital, Capital Medical University;
   University of Malaya, Malaysia
FX Supported by The Health Foundation; the Special Trustees of Moorfields
   Eye Hospital; the NIHR Biomedical Research Centre; the Royal College of
   Surgeons of Edinburgh; Fight for Sight; the Royal Blind; the Scottish
   National Institute for the War Blinded; the Wellcome Trust (WT 086868);
   The Medical Research Council UK (G0601588); the National Basic Research
   Program of China (2007CB512204); HS is a recipient of the China State
   Scholarship, the Winkler Oxford Award of China Oxford Scholarship, and
   Henry Lester Trust scholarship. HS receives funding from the Eye & ENT
   Hospital of Fudan University. QY is supported by the Beijing Institute
   of Ophthalmology, Beijing Tongren Hospital, Capital Medical University.
   TAK is supported by University of Malaya, Malaysia.
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NR 29
TC 13
Z9 13
U1 1
U2 11
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2011
VL 52
IS 13
BP 9591
EP 9597
DI 10.1167/iovs.10-6850
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 869WC
UT WOS:000298628200045
PM 22039248
DA 2022-11-30
ER

PT J
AU Schmitz-Valckenberg, S
   Bindewald-Wittich, A
   Dolar-Szczasny, J
   Dreyhaupt, J
   Wolf, S
   Scholl, HPN
   Holz, FG
AF Schmitz-Valckenberg, Steffen
   Bindewald-Wittich, Almut
   Dolar-Szczasny, Joanna
   Dreyhaupt, Jens
   Wolf, Sebastian
   Scholl, Hendrik P. N.
   Holz, Frank G.
CA Fundus Autofluorscence Age Related
TI Correlation between the area of increased autofluorescence surrounding
   geographic atrophy and disease progression in patients with AMD
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; FACTOR-H POLYMORPHISM; FUNDUS
   AUTOFLUORESCENCE; MACULAR DEGENERATION; JUNCTIONAL ZONE; RPE CELLS;
   LIPOFUSCIN; PATTERNS; RISK; CLASSIFICATION
AB PURPOSE. To test the hypothesis that the extension of areas with increased fundus autofluorescence (FAF) outside atrophic patches correlates with the rate of spread of geographic atrophy (GA) over time in eyes with age-related macular degeneration (AMD).
   METHODS. The database of the multicenter longitudinal natural history Fundus Autolluorescence in AMD (FAM) Study was reviewed for patients with GA recruited through the end of August 2003, with follow-up examinations within at least I year. Only eyes with sufficient image quality and with diffuse patterns of increased FAF surrounding atrophy were chosen. In standardized digital FAF images (excitation, 488 nm; emission, > 500 nm), total size and spread of GA was measured. The convex hull (CH) of increased FAF as the minimum polygon encompassing the entire area of increased FAF surrounding the central atrophic patches was quantified at baseline. Statistical analysis was performed with the Spearman's rank correlation coefficient (p).
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C1 Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   Tech Univ Lublin, Eye Hosp 1, Lublin, Poland.
   Heidelberg Univ, Inst Med Biometry & Appl Informat, Heidelberg, Germany.
   Univ Bern, Dept Ophthalmol, Bern, Switzerland.
   Univ Tubingen, Hosp Eye, Dept Pathophysiol Vis & Neuroophthalmol, Tubingen, Germany.
C3 University of Bonn; Lublin University of Technology; Ruprecht Karls
   University Heidelberg; University of Bern; Eberhard Karls University of
   Tubingen
RP Holz, FG (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM frank.holz@ukb.uni-bonn.de
RI Wolf, Sebastian/B-8782-2008
OI Wolf, Sebastian/0000-0002-7467-7028; Bindewald-Wittich,
   Almut/0000-0002-8151-3953; Dolar-Szczasny, Joanna/0000-0003-4206-4371
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NR 36
TC 142
Z9 149
U1 0
U2 7
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2006
VL 47
IS 6
BP 2648
EP 2654
DI 10.1167/iovs.05-0892
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 048LQ
UT WOS:000237949000052
PM 16723482
DA 2022-11-30
ER

PT J
AU Najeeb, BH
   Deak, GG
   Sacu, S
   Schmidt-Erfurth, U
   Gerendas, BS
AF Haj Najeeb, Bilal
   Deak, Gabor G.
   Sacu, Stefan
   Schmidt-Erfurth, Ursula
   Gerendas, Bianca S.
TI The RAP study, report 4: morphological and topographical characteristics
   of multifocal macular neovascularization type 3
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Retinal angiomatous proliferation; Macular neovascularization type 3;
   Neovascular age-related macular degeneration; Fluorescein angiography;
   Optical coherence tomography
ID RETINAL ANGIOMATOUS PROLIFERATION; FELLOW-EYE; RISK
AB Purpose To report on the morphological characteristics and regional distribution of multifocal macular neovascularization type 3 (mMNV3). Methods Twenty-two consecutive eyes of 21 patients with mMNV3 were included using multimodal imaging. The count and stage of lesions of all MNV types and the existence of exudate and hemorrhage were determined. Also, we addressed the regional distribution of MNV3 lesions between the superior-inferior and the nasal-temporal halves of the macula, and the range of the distance of the lesions from the central fovea. Furthermore, we explored the number of feeding vessels including the cilioretinal artery. Results We found 51 lesions in 22 eyes of 21 patients. They were bifocal in 16 (73%) eyes, trifocal in 5 (23%), and quadrifocal in one (4%). No lesion of MNV1 or 2 was found. Fifteen (68%), 2 (9%), and 16 (73%) eyes were associated with retinal hard exudate, subretinal pigment epithelium exudate, and intraretinal hemorrhage, respectively. Thirty (59%) lesions were located in the temporal half of the macula, whereas 21 (41%) were located nasally (p = 0.07). One (2%) lesion was closer than 500 mu m, 49 (96%) between 500 and 1500 mu m, and one (2%) between 1500 and 3000 mu m. The lesions were supplied by one arteriole in one (4%) eye, two arterioles in 16 (73%) eyes, and 3 arterioles in 5 (23%) eyes. The CRA contributed as a feeding vessel in 5 (23%) eyes. Conclusion The multifocal variant of MNV3 has specific morphological and topographical characteristics. Multimodal imaging allows the understanding of the pathomorphological condition in more detail.
C1 [Haj Najeeb, Bilal; Deak, Gabor G.; Sacu, Stefan; Schmidt-Erfurth, Ursula; Gerendas, Bianca S.] Med Univ Vienna, Dept Ophthalmol, Vienna Reading Ctr, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
C3 Medical University of Vienna
RP Gerendas, BS (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Vienna Reading Ctr, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM bianca.gerendas@meduniwien.ac.at
OI Haj Najeeb, Bilal/0000-0002-8147-1415; Gerendas, Bianca
   S./0000-0001-8940-8130
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NR 31
TC 3
Z9 3
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JAN
PY 2022
VL 260
IS 1
BP 141
EP 147
DI 10.1007/s00417-021-05332-8
EA AUG 2021
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YI0WK
UT WOS:000689526200002
PM 34436646
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Ghassemifar, R
   Lai, CM
   Rakoczy, PE
AF Ghassemifar, R
   Lai, CM
   Rakoczy, PE
TI VEGF differentially regulates transcription and translation of ZO-1
   alpha(+) and ZO-1 alpha(-) and mediates trans-epithelial resistance in
   cultured endothelial and epithelial cells
SO CELL AND TISSUE RESEARCH
LA English
DT Article
DE vascular endothelial growth factor; retinal pigment epithelium; ZO-1;
   permeability; quantitative real-time polymerase chain reaction;
   trans-epithelial resistance; human
ID HYPOXIA-INDUCED HYPERPERMEABILITY; JUNCTIONAL ADHESION MOLECULE;
   RETINAL-PIGMENT EPITHELIUM; GROWTH-FACTOR VEGF; TIGHT JUNCTIONS;
   VASCULAR-PERMEABILITY; INCREASED EXPRESSION; BARRIER FUNCTION; IN-VITRO;
   OCCLUDIN
AB Tight junctions (TJ) between retinal pigmented epithelial (RPE) and retinal endothelial cells maintain the outer and inner blood-retinal barrier, and the breakdown of these barriers is associated with retinal diseases. Vascular endothelial growth factor (VEGF) increases vascular permeability and is thought to be involved in age-related maculopathy. However, to date, little is known about the effect of VEGF on RPE cell junctions. We have investigated the effect of VEGF on TJ formation by examining two essential proteins, ZO-1 alpha(+) and ZO-1 alpha(-). Cultured vascular endothelial cells in the presence of 5 ng/ml VEGF significantly down-regulate ZO-1 alpha(+) and ZO-1 alpha(-) transcripts and proteins with significant loss of their trans-epithelial resistance (TER). Immunoconfocal analysis with an anti-ZO-1 antibody has confirmed the relocation of ZO-1 protein from membrane to cytoplasm. By contrast, in the presence of 5 ng/ml VEGF, cultured RPE cells (ARPE19 and RPE51) significantly up-regulate ZO-1 alpha(+) and ZO-1 alpha(-) transcripts and proteins resulting in a significant increase in their TER. Subsequent immunoconfocal analysis has demonstrated increased ZO-1 membrane assembly in VEGF-treated RPE cells. Thus, VEGF has a dual capability with respect to the regulation of the expression of some TJ proteins at the transcriptional and post-translational levels depending on cell type.
C1 Lions Eye Inst, Dept Mol Ophthalmol, Nedlands, WA 6009, Australia.
   Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
C3 Lions Eye Institute; University of Western Australia; University of
   Western Australia
RP Ghassemifar, R (通讯作者)，Lions Eye Inst, Dept Mol Ophthalmol, 2 Verdun St, Nedlands, WA 6009, Australia.
EM rezag@cyllene.uwa.edu.au
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NR 48
TC 44
Z9 45
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0302-766X
EI 1432-0878
J9 CELL TISSUE RES
JI Cell Tissue Res.
PD JAN
PY 2006
VL 323
IS 1
BP 117
EP 125
DI 10.1007/s00441-005-0046-7
PG 9
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 999YG
UT WOS:000234427500010
PM 16163490
DA 2022-11-30
ER

PT J
AU Vishwanathan, R
   Iannaccone, A
   Scott, TM
   Kritchevsky, SB
   Jennings, BJ
   Carboni, G
   Forma, G
   Satterfield, S
   Harris, T
   Johnson, KC
   Schalch, W
   Renzi, LM
   Rosano, C
   Johnson, EJ
AF Vishwanathan, Rohini
   Iannaccone, Alessandro
   Scott, Tammy M.
   Kritchevsky, Stephen B.
   Jennings, Barbara J.
   Carboni, Giovannella
   Forma, Gina
   Satterfield, Suzanne
   Harris, Tamara
   Johnson, Karen C.
   Schalch, Wolfgang
   Renzi, Lisa M.
   Rosano, Caterina
   Johnson, Elizabeth J.
TI Macular pigment optical density is related to cognitive function in
   older people
SO AGE AND AGEING
LA English
DT Article
DE lutein; zeaxanthin; cognition; macular pigment; ageing; older people
ID LUTEIN; ZEAXANTHIN; CONSUMPTION; POPULATION; DECLINE; MEMORY; FRUIT;
   SERUM
AB Background: the xanthophylls lutein (L) and zeaxanthin (Z) exist in relatively high concentration in multiple central nervous tissues (e. g. cortex and neural retina). L + Z in macula (i.e. macular pigment, MP) are thought to serve multiple functions, including protection and improvement of visual performance. Also, L + Z in the macula are related to L + Z in the cortex.
   Objective: to determine whether macular pigment optical density (MPOD, L + Z in the macula) is related to cognitive function in older adults.
   Methods: participants were older adults (n = 108, 77.6 +/- 2.7 years) sampled from the age-related maculopathy ancillary study of the Health Aging and Body Composition Study (Memphis, TN, USA). Serum carotenoids were measured using high performance liquid chromatography. MPOD was assessed using heterochromatic flicker photometry. Eight cognitive tests designed to evaluate several cognitive domains including memory and processing speed were administered. Partial correlation coefficients were computed to determine whether cognitive measures were related to serum L + Z and MPOD.
   Results: MPOD levels were significantly associated with better global cognition, verbal learning and fluency, recall, processing speed and perceptual speed, whereas serum L + Z was significantly related to only verbal fluency.
   Conclusion: MPOD is related to cognitive function in older people. Its role as a potential biomarker of cognitive function deserves further study.
C1 [Vishwanathan, Rohini; Johnson, Elizabeth J.] Tufts Univ, Carotenoids & Hlth Lab, Boston, MA 02111 USA.
   [Iannaccone, Alessandro; Jennings, Barbara J.; Carboni, Giovannella; Forma, Gina] Univ Tennessee, Ctr Hlth Sci, Hamilton Eye Inst, Memphis, TN 38163 USA.
   [Scott, Tammy M.] Tufts Univ, Nutr & Aging Lab, Boston, MA 02111 USA.
   [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
   [Carboni, Giovannella; Forma, Gina] Univ Cagliari, Ist Oftalmol, Calgliari, Italy.
   [Satterfield, Suzanne; Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
   [Harris, Tamara] NIA, NIH, Bethesda, MD 20892 USA.
   [Schalch, Wolfgang] DSM Nutr Prod, Kaiseraugst, Switzerland.
   [Renzi, Lisa M.] Univ Georgia, Dept Psychol, Athens, GA 30602 USA.
   [Rosano, Caterina] Univ Piitsburgh, Dept Epidemiol, Pittsburgh, PA 15232 USA.
C3 Tufts University; University of Tennessee System; University of
   Tennessee Health Science Center; Tufts University; Wake Forest
   University; University of Cagliari; University of Tennessee System;
   University of Tennessee Health Science Center; National Institutes of
   Health (NIH) - USA; NIH National Institute on Aging (NIA); DSM NV;
   University System of Georgia; University of Georgia
RP Johnson, EJ (通讯作者)，Tufts Univ, Carotenoids & Hlth Lab, 711 Washington St, Boston, MA 02111 USA.
EM elizabeth.johnson@tufts.edu
RI Jani, Arpit/B-5376-2017; Duarte, Graziela Biude Silva/Q-7728-2016
OI Renzi-Hammond, Lisa/0000-0003-4334-8202; Rosano,
   Caterina/0000-0002-4271-6010; Iannaccone,
   Alessandro/0000-0001-5737-8424; Rosano, Caterina/0000-0002-0909-1506
FU NIH [K23 EY000409, N01 AG62101, N01 AG62103, N01 AG62106]; International
   Retinal Research Foundation; Research to Prevent Blindness; American
   Health Assistance Foundation; DSM; NATIONAL EYE INSTITUTE [K23EY000409]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGING [N01AG062103,
   N01AG062106, N01AG062101] Funding Source: NIH RePORTER
FX This work was supported by NIH grant K23 EY000409 (A. I.), and by NIH
   contracts N01 AG62101, N01 AG62103 and N01 AG62106 (Health ABC Study);
   by the International Retinal Research Foundation (A. I.), by Research to
   Prevent Blindness (Career Development Award to A. I. and unrestricted
   grant to UTHSC Hamilton Eye Institute), by the American Health
   Assistance Foundation and by DSM. The instrument utilised to measure
   MPOD in this study was generously donated by Bausch and Lomb and Kemin
   Foods. Portions of these findings have been presented at the Association
   for Research in Vision and Ophthalmology Annual Meeting (2007) and at
   the Experimental Biology Annual Meeting (2008).
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NR 27
TC 97
Z9 99
U1 0
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
EI 1468-2834
J9 AGE AGEING
JI Age Ageing
PD MAR
PY 2014
VL 43
IS 2
BP 271
EP 275
DI 10.1093/ageing/aft210
PG 6
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA AB8GP
UT WOS:000332028600023
PM 24435852
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Najeeb, BH
   Deak, G
   Schmidt-Erfurth, U
   Gerendas, BS
AF Najeeb, Bilal Haj
   Deak, Gabor
   Schmidt-Erfurth, Ursula
   Gerendas, Bianca S.
TI THE RAP STUDY, REPORT TWO The Regional Distribution of Macular
   Neovascularization Type 3, a Novel Insight Into Its Etiology
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE type 3 choroidal neovascularization; macular neovascularization; optical
   coherence tomography; retinal angiomatous proliferation; fluorescein
   angiography
AB Purpose: To explore the regional distribution of macular neovascularization type 3 (MNV3).
   Methods: Seventy-eight eyes of 78 patients were reviewed. We defined the location of each lesion after applying a modified ETDRS grid and the incidence of simultaneous MNV1 or 2. Also, we investigated the distribution of MNV3 at the outline of the foveal avascular zone and when the diameter of foveal avascular zone was less than 325 mm.
   Results: The distribution of MNV3 was 4 lesions (5%) from the center to 500 mm, 72 (92%) from 500 mm to 1500 mm, and 2 (3%) from 1,500 mm to 3000 mm. The distribution in respect of the ETDRS fields was 7 (9%) nasal, 16 (20%) superior, 32 (40%) temporal, and 23 (31%) inferior. No additional MNV1 or 2 were found elsewhere. Most lesions tended to distribute along straight bands radiating from the perifoveal area, mainly in the temporal half (72%). None of the cases had MNV3 at the boundary of the foveal avascular zone. Only five cases had foveal avascular zone diameter of less than 325 mm, the closest lesion was 425 mm away from the center.
   Conclusion: MNV3 lesions are most likely neither symmetrical nor uniformly distributed. They have a higher affinity to distribute radially in the temporal perifoveal area.
C1 [Najeeb, Bilal Haj; Deak, Gabor; Schmidt-Erfurth, Ursula; Gerendas, Bianca S.] Med Univ Vienna, Dept Ophthalmol, Vienna Reading Ctr, Vienna, Austria.
C3 Medical University of Vienna
RP Schmidt-Erfurth, U (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM Ursula.schmidt-erfurth@meduniwien.ac.at
OI Haj Najeeb, Bilal/0000-0002-8147-1415
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NR 39
TC 9
Z9 9
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD DEC
PY 2020
VL 40
IS 12
BP 2255
EP 2262
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QI4NW
UT WOS:000618957100001
PM 32032256
DA 2022-11-30
ER

PT J
AU Manayath, GJ
   Ranjan, R
   Vidhate, S
   Narendran, V
AF Manayath, George Joseph
   Ranjan, Ratnesh
   Vidhate, Swapnil
   Narendran, Venkatapathy
TI PHOTODYNAMIC THERAPY-INDUCED ACUTE EXUDATIVE MACULOPATHY Incidence,
   Clinical Features, and Long-Term Outcomes
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE AMD; CSC; PDT; PAEM; PCV
ID VISUAL-ACUITY; COMPLICATIONS; DECREASE
AB Purpose: To describe the incidence, clinical features, and long-term outcomes of photodynamic therapy (PDT)-induced acute exudative maculopathy (PAEM) in patients who underwent PDT for various indications. Methods: This retrospective observational case series included all cases who developed massive serofibrinous macular exudation within a week after PDT. Medical records of patients with post-PDT exudative events were reviewed for relevant data and imaging abstraction including optical coherence tomography and indocyanine green angiography features and were subjected to analysis. Results: The incidence rate of PAEM was 4.52%, being noted in 8 eyes (out of 177 PDT sessions in 155 eyes) with a mean age of 70.25 +/- 6.65 years. Pre-PDT factors commonly associated with PAEM included age >= 65 years (87.5%), clinical diagnosis of polypoidal choroidal vasculopathy (75%), spot size >= 3,500 mu m (100%), best-corrected visual acuity of 20/40 or better (87.5%), low-fluence PDT (87.5%), and the first exposure to PDT (75%). Photodynamic therapy-induced acute exudative maculopathy was noted at a mean interval of 2.9 +/- 1.7 days (2-7 days) after PDT. Photodynamic therapy-induced acute exudative maculopathy resulted in significant decrease in mean best-corrected visual acuity from logMAR 0.29 +/- 0.21 (approximate Snellen equivalent 20/39) to logMAR 0.91 +/- 0.37 (approximate Snellen equivalent 20/163) [P = 0.0018], and significant increase in mean central macular thickness from 228.1 +/- 71.8 mu m to 481.4 +/- 154.8 mu m (P = 0.0029). Photodynamic therapy-induced acute exudative maculopathy resolved to baseline or even better tomographic status at a mean interval of 4.6 +/- 1.2 weeks, resulting in complete visual recovery compared with baseline. During mean follow-up of 77.8 +/- 46.4 weeks after PDT, no activity was noted for a mean duration of 26.3 +/- 42.5 weeks after resolution. At final visit, mean best-corrected visual acuity and central macular thickness was logMAR 0.49 +/- 0.28 (approximate Snellen equivalent 20/62) and 153.6 +/- 40.0 mu m, respectively, with underlying pathology being stable in 50% of the eyes. Conclusion: Photodynamic therapy-induced acute exudative maculopathy is an uncommon complication with self-resolving course and favorable prognosis. Patients undergoing PDT should be warned of the possibility of PAEM. The factors frequently associated with PAEM include elderly age (>65 years), clinical diagnosis of polypoidal choroidal vasculopathy, larger spot size (>= 3,500 mu m), pre-PDT best-corrected visual acuity of 20/40 or better, low-fluence PDT, and the first exposure to PDT.
C1 Aravind Eye Hosp, Dept Vitreoretina, Coimbatore, Tamil Nadu, India.
   Postgrad Inst Ophthalmol, Coimbatore, Tamil Nadu, India.
RP Ranjan, R (通讯作者)，Aravind Eye Hosp, Postgrad Inst Ophthalmol, Dept Vitreoretina, Coimbatore 641014, Tamil Nadu, India.
EM drratnesh16@gmail.com
OI Ranjan, Ratnesh/0000-0002-9410-4649
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NR 22
TC 7
Z9 7
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD JAN
PY 2020
VL 40
IS 1
BP 135
EP 144
DI 10.1097/IAE.0000000000002343
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LA1PT
UT WOS:000523727600017
PM 30312256
DA 2022-11-30
ER

PT J
AU Cheung, CMG
   Lee, WK
   Koizumi, H
   Dansingani, K
   Lai, TYY
   Freund, KB
AF Cheung, Chui Ming Gemmy
   Lee, Won Ki
   Koizumi, Hideki
   Dansingani, Kunal
   Lai, Timothy Y. Y.
   Freund, K. Bailey
TI Pachychoroid disease
SO EYE
LA English
DT Review
ID CENTRAL SEROUS CHORIORETINOPATHY; POLYPOIDAL CHOROIDAL VASCULOPATHY;
   OPTICAL COHERENCE TOMOGRAPHY; VERTEPORFIN PHOTODYNAMIC THERAPY;
   INDOCYANINE-GREEN VIDEOANGIOGRAPHY; ENDOTHELIAL GROWTH-FACTOR; MACULAR
   DEGENERATION; MICROPULSE PHOTOCOAGULATION; MINERALOCORTICOID RECEPTOR;
   SPECTRUM DISORDERS
AB Pachychoroid is a relatively novel concept describing a phenotype characterized by attenuation of the choriocapillaris overlying dilated choroidal veins, and associated with progressive retinal pigment epithelium dysfunction and neovascularization. The emphasis in defining pachychoroid-related disorders has shifted away from simply an abnormally thick choroid (pachychoroid) toward a detailed morphological definition of a pathologic state (pachychoroid disease) with functional implications, which will be discussed in this review. Several clinical manifestations have been described to reside within the pachychoroid disease spectrum, including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization, focal choroidal excavation, peripapillary pachychoroid syndrome. These conditions all exhibit the characteristic choroidal alterations and are believed to represent different manifestations of a common pathogenic process. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical and imaging features, management considerations, as well as current understanding of pathogenesis of these disorders within the context of the recent findings related to pachychoroid disease.
C1 [Cheung, Chui Ming Gemmy] Singapore Natl Eye Ctr, Singapore, Singapore.
   [Cheung, Chui Ming Gemmy] Singapore Eye Res Inst, Singapore, Singapore.
   [Cheung, Chui Ming Gemmy] Duke NUS Med Sch, Singapore, Singapore.
   [Lee, Won Ki] Catholic Univ Korea, Seoul St Marys Hosp, Dept Ophthalmol, Coll Med, Seoul, South Korea.
   [Koizumi, Hideki] Univ Ryukyus, Grad Sch Med, Dept Ophthalmol, Nishihara, Okinawa, Japan.
   [Dansingani, Kunal] Univ Pittsburgh, Dept Ophthalmol, Med Ctr, Pittsburgh, PA 15260 USA.
   [Lai, Timothy Y. Y.] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Shatin, Hong Kong, Peoples R China.
   [Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY USA.
   [Freund, K. Bailey] LuEsther T Mertz Retinal Res Ctr, New York, NY USA.
   [Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY USA.
C3 Singapore National Eye Center; National University of Singapore;
   Singapore National Eye Center; National University of Singapore;
   Catholic University of Korea; Seoul St. Mary's Hospital; University of
   Ryukyus; Pennsylvania Commonwealth System of Higher Education (PCSHE);
   University of Pittsburgh; Chinese University of Hong Kong; Vitreous
   Retina Macula Consultants of New York; New York University
RP Cheung, CMG (通讯作者)，Singapore Natl Eye Ctr, Singapore, Singapore.; Cheung, CMG (通讯作者)，Singapore Eye Res Inst, Singapore, Singapore.; Cheung, CMG (通讯作者)，Duke NUS Med Sch, Singapore, Singapore.
EM gemmy.cheung.c.m@snec.com.sg
RI Dansingani, Kunal K/D-1025-2015; Lai, Timothy Y Y/AAC-2120-2020; Freund,
   K. Bailey/V-7488-2018
OI Lai, Timothy Y Y/0000-0002-7832-6428; Cheung, Chui Ming
   Gemmy/0000-0003-3358-3516; Freund, K. Bailey/0000-0002-7888-9773
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NR 114
TC 276
Z9 279
U1 2
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD JAN
PY 2019
VL 33
IS 1
BP 14
EP 33
DI 10.1038/s41433-018-0158-4
PG 20
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HG9YX
UT WOS:000455369700003
PM 29995841
OA Green Published, Bronze
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Wang, TY
   Wan, ZQ
   Peng, Q
AF Wang, Tian-Yu
   Wan, Zhong-Qi
   Peng, Qing
TI A patient misdiagnosed with central serous chorioretinopathy: A case
   report
SO WORLD JOURNAL OF CLINICAL CASES
LA English
DT Article
DE Central serous chorioretinopathy; Polypoidal choroidal vasculopathy;
   Optical coherence tomography; Case report
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; MACULAR DEGENERATION
AB BACKGROUND
   Due to some similarities in the manifestations between central serous chorioretinopathy (CSC) and polypoidal choroidal vasculopathy (PCV), PCV may be misdiagnosed as CSC. More attention should be paid to distinguishing these two disorders.
   CASE SUMMARY
   A 52-year-old woman presented to our hospital with blurred vision in her left eye for approximately 1 wk. Anterior segment and intraocular pressure findings were normal in both eyes. Fundus photography of the left eye showed a seemingly normal adult oculus fundus without any obvious hard exudate or hemorrhage. Optical coherence tomography exhibited a hypo-reflective space beneath both the neurosensory retina and the pigment epithelium layer. The late phase of fluorescein angiography revealed increased leakage. The patient was initially diagnosed with CSC. At follow-up, however, the final diagnosis turned out to be PCV.
   CONCLUSION
   CSC and PCV are two different retinal entities. Lipid deposition and hemorrhage are the most important elements that lead to confusion between these two entities. Indocyanine green angiography should be performed to make a definitive diagnosis, especially in cases with suspected PCV.
C1 [Wang, Tian-Yu] Fudan Univ, Minhang Hosp, Dept Ophthalmol, Shanghai 201199, Peoples R China.
   [Wan, Zhong-Qi] Nanjing Med Univ, Sch Publ Hlth, Nanjing 211166, Jiangsu, Peoples R China.
   [Peng, Qing] Tongji Univ, Peoples Hosp Shanghai 10, Dept Ophthalmol, 301 Middle Yanchang Rd, Shanghai 200072, Peoples R China.
C3 Fudan University; Nanjing Medical University; Tongji University
RP Peng, Q (通讯作者)，Tongji Univ, Peoples Hosp Shanghai 10, Dept Ophthalmol, 301 Middle Yanchang Rd, Shanghai 200072, Peoples R China.
EM drqingpeng@126.com
OI Peng, Qing/0000-0002-6991-9432; Wang, Tianyu/0000-0001-6107-7739
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NR 10
TC 0
Z9 0
U1 1
U2 2
PU BAISHIDENG PUBLISHING GROUP INC
PI PLEASANTON
PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA
SN 2307-8960
J9 WORLD J CLIN CASES
JI World J. Clin. Cases
PD AUG 26
PY 2019
VL 7
IS 16
BP 2341
EP 2345
DI 10.12998/wjcc.v7.i16.2341
PG 5
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA IU1VG
UT WOS:000483364100021
PM 31531329
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Arrigo, A
   Calamuneri, A
   Aragona, E
   Bordato, A
   Moretti, AG
   Amato, A
   Bandello, F
   Parodi, MB
AF Arrigo, Alessandro
   Calamuneri, Alessandro
   Aragona, Emanuela
   Bordato, Alessandro
   Grazioli Moretti, Alessio
   Amato, Alessia
   Bandello, Francesco
   Battaglia Parodi, Maurizio
TI Structural OCT Parameters Associated with Treatment Response and Macular
   Neovascularization Onset in Central Serous Chorioretinopathy
SO OPHTHALMOLOGY AND THERAPY
LA English
DT Article
DE Artificial intelligence; Central serous chorioretinopathy; Eplerenone;
   OCT; Photodynamic therapy; Treatment response
ID EPLERENONE; OUTCOMES; PLACEBO
AB Introduction This study aimed to assess quantitative factors associated with treatment response and macular neovascularization (MNV) onset in central serous chorioretinopathy (CSC) through an artificial intelligence-based approach. Methods The study was designed as an interventional, prospective case series with a planned follow-up of 36 months. We included only eyes demonstrating the first episode of CSC. All the patients underwent eplerenone or photodynamic therapy (PDT) treatment. Eyes developing MNV underwent anti-VEGF injections. We developed an artificial intelligence-based model to assess predictive quantitative structural optical coherence tomography (OCT) factors related to treatment response and onset of MNV. Main outcome measures were best-correct visual acuity (BCVA), central macular thickness (CMT), retinal thickness (RT), retinal pigment epithelium (RPE) thickness, choroidal thickness, Sattler's layer thickness (SLT), Haller's layer thickness, retinal and choroidal hyperreflective foci (HF), and MNV. Results We included 96 naive CSC eyes (96 patients). Baseline BCVA was 0.18 +/- 0.25 logMAR, which increased to 0.16 +/- 0.27 logMAR after 3 years (p > 0.05). Baseline CMT was 337 +/- 126 mu m, which improved to 229 +/- 40 mu m after 3 years (p < 0.01). We observed good response to eplerenone in 40/78 (51%) eyes, whereas 38/78 (49%) eyes underwent PDT. The artificial intelligence model showed choroidal HF and age as determining factors of good response to eplerenone or PDT. RPE thickness < 36 mu m, RT < 300 mu m, and SLT < 50 mu m increased probability of 50% of having MNV. Conclusions CSC response to eplerenone or PDT is influenced by choroidal HF and patient age. RPE and SLT represent relevant factors for onset of MNV.
C1 [Arrigo, Alessandro; Aragona, Emanuela; Bordato, Alessandro; Grazioli Moretti, Alessio; Amato, Alessia; Bandello, Francesco; Battaglia Parodi, Maurizio] Univ Vita Salute, IRCCS Osped San Raffaele, Dept Ophthalmol, Milan, Italy.
   [Calamuneri, Alessandro] Univ Messina, Messina, Italy.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele;
   University of Messina
RP Arrigo, A (通讯作者)，Univ Vita Salute, IRCCS Osped San Raffaele, Dept Ophthalmol, Milan, Italy.
EM alessandro.arrigo@hotmail.com
OI Arrigo, Alessandro/0000-0003-4715-8414; bandello,
   francesco/0000-0003-3238-9682; Battaglia Parodi,
   Maurizio/0000-0002-0385-7961
CR Akaike H., 1973, P 2 INT S INF THEOR, P267, DOI 10.1007/978-1-4612-1694-0
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NR 20
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER INT PUBL AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2193-8245
EI 2193-6528
J9 OPHTHALMOL THER
JI OPHTHALMOL. THER.
PD JUN
PY 2021
VL 10
IS 2
BP 289
EP 298
DI 10.1007/s40123-021-00336-3
EA FEB 2021
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RU0LP
UT WOS:000619688400001
PM 33606200
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Bergman, B
   Nilsson-Ehle, H
   Sjostrand, J
AF Bergman, B
   Nilsson-Ehle, H
   Sjostrand, J
TI Ocular changes, risk markers for eye disorders and effects of cataract
   surgery in elderly people: a study of an urban Swedish population
   followed from 70 to 97 years of age
SO ACTA OPHTHALMOLOGICA SCANDINAVICA
LA English
DT Article
DE age-related ocular changes; aged; eye disorders; visual acuity; cataract
   surgery; longitudinal population study; risk markers
ID BLUE-MOUNTAINS-EYE; BEAVER DAM EYE; VISUAL IMPAIRMENT; MACULAR
   DEGENERATION; REFERENCE INTERVALS; BRITISH POPULATION; 10-YEAR
   INCIDENCE; 5-YEAR INCIDENCE; PREVALENCE; MACULOPATHY
AB Aims: To investigate the prevalence of and potential risk factors for ocular disorders and the effects of timing of cataract surgery from age 70-97 years.
   Population: A representative population sample taken from within the Gerontological and Geriatric Population Studies (H 70) in Gothenburg, Sweden (n = 958). All subjects underwent eye examinations at age 70 years in 1971 and subsequently at ages 82, 88, 95 and 97 years. All inhabitants of Gothenburg aged 95 and 97 years were invited to participate in the study.
   Results: Decreased vision (visual acuity less than or equal to 0.5) was found in 20% and 80% of subjects at ages 82 and 97 years, respectively. Blood folate and physical activity at age 70 years correlated positively and body mass index (BMI) negatively to visual acuity (VA) greater than or equal to 0.8 at ages 82 and 88 years. Smoking at age 70 years correlated to early age-related maculopathy (ARM). Cataract surgery had been performed in 40% of subjects at age 97 years. Surgery 2 years earlier led to a 15% increase in time spent with improved vision.
   Conclusions: The deterioration of vision in elderly people is a major health problem, for which 'low' folate status, smoking, 'high' BMI and low physical activity are potential risk factors. Early cataract surgery is also beneficial in very old patients.
C1 Univ Gothenburg, Dept Ophthalmol, Inst Clin Neurosci, Sahlgrenska Acad, Gothenburg, Sweden.
   Univ Gothenburg, Sect Haematol & Coagulat, Inst Internal Med, Sahlgrenska Acad, Gothenburg, Sweden.
C3 University of Gothenburg; University of Gothenburg
RP Bergman, B (通讯作者)，Sahlgrens Univ Hosp, Dept Ophthalmol, SE-43180 Molndal, Sweden.
EM birgitta.bergman@oft.gu.se
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NR 48
TC 27
Z9 27
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1395-3907
J9 ACTA OPHTHALMOL SCAN
JI Acta Ophthalmol. Scand.
PD APR
PY 2004
VL 82
IS 2
BP 166
EP 174
DI 10.1111/j.1600-0420.2004.00182.x
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 806HT
UT WOS:000220425700011
PM 15043535
DA 2022-11-30
ER

PT J
AU Amaro, MH
   Roller, AB
   Motta, CTPD
   Motta, MMD
AF Amaro, Miguel Hage
   Roller, Aaron Brock
   dos Santos Motta, Cesar Tavares Pereira
   dos Santos Motta, Mario Martins
TI Polypoidal choroidal vasculopathy causing cystoid macular edema and the
   response to ranibizumb intravitreal treatment
SO REVISTA BRASILEIRA DE OFTALMOLOGIA
LA English
DT Article
DE Choroid diseases/drug therapy; Polypoidal choroidal vasculopathy/drug
   therapy Macular edema/etiology; Injections; Antibodies,
   monoclonal/therapeutic use; Case report
ID PIGMENT EPITHELIAL DETACHMENTS; PHOTODYNAMIC THERAPY; DEGENERATION;
   BEVACIZUMAB
AB Purpose: To report a polypoidal vascular choroidopathy clinical case causing cystoid macular edema and the response to Ranibizumab intravitreal treatment. Methods: A 62-year old caucasian woman was referred by her comprehensive ophthalmologist for retinal avaliation. On presentation best corrected visual acuity was 20/100 in the left eye and 20/20 in right eye. Anterior segment examination was unremarkable in both eyes. Clinical examination and FA on the left eye demonstrated numerous small drusen and a cystoid macular edema due leakage from any polips in justapapilar region and from polips in the superior arcade vascular region and subretinal fluid and cystic change in the OCT. The right eye had FA normal. The patient refused to submitt a ICGV angiography. The patient was treated by intravitreal ranibizumab injections in the left eye every 4 weeks, 3 injections, three months. Results: The patient showed resolution both of cystic change and subretinal fluid in the OCT, and the visual acuity in the six months follow-up improved to 20/25. The patient was followed by 18 months at this time and the visual acuity remained stable 20/25. Conclusion: We reported a patient case of cystoid macular edema from a polypoidal choroidal vaculopathy that responded well to ranibizumab intravitreal injection as monotheraphy with disappearance of the initial subretinal fluid and cystic change in OCT follow-up and stop the polips.
C1 [Roller, Aaron Brock] Univ Iowa, Dept Ophthalmol, Iowa City, IA 52242 USA.
   [dos Santos Motta, Cesar Tavares Pereira; dos Santos Motta, Mario Martins] Univ Rio Janeiro UNIRIO, Rio De Janeiro, Brazil.
C3 University of Iowa; Universidade Federal do Estado do Rio de Janeiro
RP Amaro, MH (通讯作者)，Quintino Bocaiuva 516, BR-66053240 Belem, Para, Brazil.
EM miguelhamaro@yahoo.com.br
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NR 24
TC 0
Z9 0
U1 0
U2 0
PU SOC BRASILEIRA OFTALMOLOGIA
PI RIO DE JANEIRO
PA RUA SAO SALVADOR 107, RIO DE JANEIRO, 22231-170, BRAZIL
SN 0034-7280
J9 REV BRAS OFTALMOL
JI Rev. Bras. Oftalmol.
PD JUL-AUG
PY 2011
VL 70
IS 4
BP 252
EP 256
DI 10.1590/S0034-72802011000400010
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 831II
UT WOS:000295722900010
OA gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Huang, GH
AF Huang, Guan-Hua
TI Integrated analysis of incidence, progression, regression and
   disappearance probabilities
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
ID BEAVER DAM EYE; AGE-RELATED MACULOPATHY; ORDINAL MEASUREMENTS;
   LONGITUDINAL DATA; VISUAL-ACUITY; MODELS
AB Background: Age-related maculopathy (ARM) is a leading cause of vision loss in people aged 65 or older. ARM is distinctive in that it is a disease which can transition through incidence, progression, regression and disappearance. The purpose of this study is to develop methodologies for studying the relationship of risk factors with different transition probabilities.
   Methods: Our framework for studying this relationship includes two different analytical approaches. In the first approach, one can define, model and estimate the relationship between each transition probability and risk factors separately. This approach is similar to constraining a population to a certain disease status at the baseline, and then analyzing the probability of the constrained population to develop a different status. While this approach is intuitive, one risks losing available information while at the same time running into the problem of insufficient sample size. The second approach specifies a transition model for analyzing such a disease. This model provides the conditional probability of a current disease status based upon a previous status, and can therefore jointly analyze all transition probabilities. Throughout the paper, an analysis to determine the birth cohort effect on ARM is used as an illustration.
   Results and conclusion: This study has found parallel separate and joint analyses to be more enlightening than any analysis in isolation. By implementing both approaches, one can obtain more reliable and more efficient results.
C1 Natl Chiao Tung Univ, Inst Stat, Hsinchu, Taiwan.
C3 National Yang Ming Chiao Tung University
RP Huang, GH (通讯作者)，Natl Chiao Tung Univ, Inst Stat, Hsinchu, Taiwan.
EM ghuang@stat.nctu.edu.tw
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NR 23
TC 2
Z9 3
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD JUN 25
PY 2008
VL 8
AR 40
DI 10.1186/1471-2288-8-40
PG 12
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA 335PK
UT WOS:000258302300001
PM 18577235
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Liu, B
   Zhang, XZ
   Peng, YT
   Mi, L
   Wen, F
AF Liu, Bing
   Zhang, Xiongze
   Peng, Yuting
   Mi, Lan
   Wen, Feng
TI Etiologies and Characteristics of Choroidal Neovascularization in Young
   Chinese Patients
SO OPHTHALMOLOGICA
LA English
DT Article
DE Choroidal neovascularization; Etiology; Young Chinese patients
ID CENTRAL SEROUS CHORIORETINOPATHY; MACULAR DEGENERATION; PHOTODYNAMIC
   THERAPY; CLINICAL CHARACTERISTICS; VISUAL PROGNOSIS; VASCULOPATHY;
   RANIBIZUMAB; THICKNESS; DIAGNOSIS; FEATURES
AB Purpose: To investigate the etiologies and characteristics of choroidal neovascularization (CNV) in young Chinese patients. Methods: A retrospective review of young Chinese patients (<50 years of age) with CNV from January 2010 to June 2016 was performed. Results: Of the 501 patients (537 eyes) with CNV, 58.7% were female, and 7.2% had bilateral CNV. The mean age was 35 years. The etiologies were idiopathic CNV (ICNV, 43.9%), pathologic myopia (PM, 21.9%), punctate inner choroidopathy (PIC, 17.4%), polypoidal choroidal vasculopathy (4.4%), multifocal choroiditis with panuveitis (3.6%), and other disorders (8.8%). Five hundred and six CNVs (94.2%) showed a predominantly classic CNV composition on fundus fluorescein angiography (FFA) and 316 CNVs (96.6%) were type 2 CNV on optical coherence tomography (OCT). Conclusion: The etiologies of CNV in young Chinese patients were diverse, and ICNV, PM, and PIC were the three most common etiologies. Most CNVs were classic on FFA and type 2 on OCT. (C) 2018 S. Karger AG, Basel
C1 [Liu, Bing; Zhang, Xiongze; Peng, Yuting; Mi, Lan; Wen, Feng] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 South Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
C3 Sun Yat Sen University
RP Wen, F (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 South Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
EM wenfeng208@foxmail.com
FU National Natural Science Foundation of China [81570831]; Fundamental
   Research Funds of the State Key Laboratory of Ophthalmology
FX This work was supported by the National Natural Science Foundation of
   China (grant No. 81570831) and the Fundamental Research Funds of the
   State Key Laboratory of Ophthalmology.
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NR 38
TC 2
Z9 2
U1 0
U2 5
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
EI 1423-0267
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2019
VL 241
IS 2
BP 73
EP 80
DI 10.1159/000492133
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HM5LS
UT WOS:000459517800002
PM 30153680
DA 2022-11-30
ER

PT J
AU Yoon, W
   Yoon, J
   Na, SK
   Lee, J
   Kim, J
   Kim, JW
   Cho, HJ
AF Yoon, Wontae
   Yoon, Jihyun
   Na, Seung Kwan
   Lee, Jihyun
   Kim, Jaemin
   Kim, Jong Woo
   Cho, Han Joo
TI Impact of macular fluid features on outcomes of anti-vascular
   endothelial growth factor treatment for type 3 macular
   neovascularization
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PIGMENT EPITHELIAL DETACHMENT; OPTICAL COHERENCE TOMOGRAPHY;
   VISUAL-ACUITY; RANIBIZUMAB INJECTIONS; DEGENERATION
AB We evaluated the impact of macular fluid features on visual and anatomical outcomes in type 3 macular neovascularization (MNV) patients treated with anti-vascular endothelial growth factor (VEGF). We retrospectively enrolled 89 eyes with type 3 MNV with at least 12 months of follow-up. All patients were treatment-naive and received a monthly loading injection of anti-VEGF for three months, followed by further injections as required. The association of baseline macular morphology, including intraretinal fluid (IRF) and subretinal fluid (SRF), with visual and anatomical outcomes was analyzed. At baseline, IRF was present in all enrolled patients (100%), and SRF was present in 43.8% (39/89) of them. After 12 months of treatment, no significant difference was found in terms of best-corrected visual acuity (BCVA) and changes in central foveal thickness between the eyes with (39) and without (50) SRF at baseline. In addition, the proportion of improved or worsened (gain or loss of more than three lines in the BCVA) visual acuity at 12 months was not significantly different among the groups. Incidence of macular atrophy during the treatment showed no difference between the groups, regardless of the presence of SRF. In conclusion, the macular fluid morphology, specifically SRF, in type 3 MNV showed no significant correlation with visual and anatomical outcomes during anti-VEGF treatment.
C1 [Yoon, Wontae; Yoon, Jihyun; Na, Seung Kwan; Lee, Jihyun; Kim, Jaemin; Kim, Jong Woo; Cho, Han Joo] Konyang Univ, Kims Eye Hosp, Coll Med, 156,4ga, Seoul, South Korea.
C3 Konyang University; Konyang University Hospital
RP Cho, HJ (通讯作者)，Konyang Univ, Kims Eye Hosp, Coll Med, 156,4ga, Seoul, South Korea.
EM chojoo@kimeye.com
FU Kim's Eye Hospital Research Center
FX This study was supported by Kim's Eye Hospital Research Center.
CR Borrelli E, 2018, RETINA-J RET VIT DIS, V38, P1968, DOI 10.1097/IAE.0000000000002198
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NR 29
TC 0
Z9 0
U1 0
U2 0
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD DEC 8
PY 2021
VL 11
IS 1
AR 23643
DI 10.1038/s41598-021-03053-w
PG 7
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA XU8RD
UT WOS:000734524200085
PM 34880302
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sacconi, R
   Forte, P
   Capuano, V
   Miere, A
   Costanzo, E
   Tombolini, B
   Fantaguzzi, F
   Jung, C
   Parravano, M
   Varano, M
   Souied, E
   Bandello, F
   Querques, G
AF Sacconi, Riccardo
   Forte, Paolo
   Capuano, Vittorio
   Miere, Alexandra
   Costanzo, Eliana
   Tombolini, Beatrice
   Fantaguzzi, Federico
   Jung, Camille
   Parravano, Mariacristina
   Varano, Monica
   Souied, Eric
   Bandello, Francesco
   Querques, Giuseppe
TI OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CHARACTERIZATION OF EVOLVING
   LESIONS IN FELLOW EYES OF EXUDATIVE TYPE 3 MACULAR NEOVASCULARIZATION
   PATIENTS
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; biomarker; multimodal imaging; nascent
   type 3; OCTA; optical coherence tomography angiography; RAP; type 3
   neovascularization
ID RETINAL ANGIOMATOUS PROLIFERATION; OCT ANGIOGRAPHY
AB Purpose: To investigate fellow eyes of newly diagnosed unilateral exudative Type 3 (T3) macular neovascularization (MNV) patients by assessing the presence and progression of a preclinical neovascular component during a 3-year follow-up. Methods: This is a longitudinal study involving three retinal referral centers. Patients affected by unilateral exudative treatment-naive T3 MNV were enrolled. Results: Twenty-four eyes of 24 patients (79 +/- 6 years old) were enrolled. Nine eyes (37%) displayed a nonexudative T3 MNV at baseline that developed exudation after a mean of 9 +/- 9 months. Fifteen eyes that did not display a nonexudative Type 3 MNV at baseline. Five eyes (21%) did not display neovessels at baseline, but showed a nonexudative T3 after 13 +/- 9 months, and exudation after 8 +/- 3 months. Five eyes (21%) developed active exudative T3 MNV after 23 +/- 9 months, with no detectable nonexudative stage at baseline. Five eyes (21%) did not show MNV, but progressed to geographic atrophy by 36 months of follow-up. Overall, T3 MNV in the fellow eye accounted for 79%, all developing exudation over 3 years of follow-up. Conclusion: The occurrence of a nonexudative T3 MNV is a frequent event in the fellow eye of patients newly diagnosed with unilateral exudative T3 MNV and it precedes the development of exudation over 3 years (prevalence of 37% and cumulative incidence of 79%). Optical coherence tomography angiography approach may be used to perform an early diagnosis and treatment of patients with T3 MNV.
C1 [Sacconi, Riccardo; Forte, Paolo; Tombolini, Beatrice; Fantaguzzi, Federico; Bandello, Francesco; Querques, Giuseppe] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy.
   [Sacconi, Riccardo; Forte, Paolo; Tombolini, Beatrice; Fantaguzzi, Federico; Bandello, Francesco; Querques, Giuseppe] IRCCS, Div Head & Neck, Ophthalmol Unit, San Raffaele Sci Inst, Milan, Italy.
   [Sacconi, Riccardo; Capuano, Vittorio; Miere, Alexandra; Jung, Camille; Souied, Eric] GRC Macula & Biol Ressources Ctr, Clin Res Ctr, Creteil, France.
   [Capuano, Vittorio; Miere, Alexandra; Souied, Eric] Univ Paris Est Creteil, Hosp Intercommunal Creteil, Dept Ophthalmol, Creteil, France.
   [Costanzo, Eliana; Parravano, Mariacristina; Varano, Monica] IRCCS, Fdn GB Bietti, Rome, Italy.
C3 Vita-Salute San Raffaele University; Vita-Salute San Raffaele
   University; IRCCS Ospedale San Raffaele; Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil; IRCCS - Fondazione
   "G.B. Bietti" per lo Studio e la Ricerca in Oftalmologia
RP Querques, G (通讯作者)，Univ Vita Salute, Dept Ophthalmol, IRCCS, Osped San Raffaele, Via Olgettina 60, I-20132 Milan, Italy.
EM querques.giuseppe@hsr.it
CR Ahmed D, 2021, J OPHTHALMOL, V2021, DOI 10.1155/2021/6695918
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NR 29
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD NOV
PY 2022
VL 42
IS 11
BP 2075
EP 2082
DI 10.1097/IAE.0000000000003598
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5M0WB
UT WOS:000870825900010
PM 35962996
DA 2022-11-30
ER

PT J
AU Granado-Lorencio, F
   Herrero-Barbudo, C
   Olmedilla-Alonso, B
   Blanco-Navarro, I
   Perez-Sacristan, B
AF Granado-Lorencio, F.
   Herrero-Barbudo, C.
   Olmedilla-Alonso, B.
   Blanco-Navarro, I.
   Perez-Sacristan, B.
TI Hypocarotenemia After Bariatric Surgery: A Preliminary Study
SO OBESITY SURGERY
LA English
DT Article
DE Obesity surgery; Lutein; beta-cryptoxanthin; beta-carotene; Lycopene;
   Fat-soluble vitamins
ID MAIN CAROTENOIDS; GASTRIC BYPASS; SERUM; METABOLISM; OBESITY;
   TOCOPHEROL; LYCOPENE; OUTCOMES; RETINOL; CALCIUM
AB Dietary carotenoids have attracted a great deal of attention due to their potential clinical relevance in conditions such as age-related maculopathy, osteoporosis, cardiovascular disease, and cancer. Surgical procedures have become the primary treatment of severe obesity, although nutrient deficiencies are common and long-term metabolic sequelae remain unknown. Thus, our aim was to assess the carotenoid status in serum of subjects after obesity surgery.
   We evaluated the status of lutein, zeaxanthin, alpha- and beta-cryptoxanthin, lycopene, alpha- and beta-carotene, and fat-soluble vitamins by a quality-controlled high-performance liquid chromatography method in serum of 53 patients. Subjects were consecutively included as they were monitored for nutritional status after Roux-en-Y gastric bypass (RYGBP) or biliopancreatic diversion (BPD). Average follow-up time was 18 and 14 months for each protocol, respectively.
   After obesity surgery, a consistent and continuous decline in all carotenoids to almost undetectable levels occurs, especially in those who underwent BPD diversion who, on average, displayed serum levels about one half to one third of those found in RYGBP patients.
   The hypocarotenemia observed after bariatric surgery may compromise the availability of carotenoids to tissues and the vitamin A status, reducing the fat-soluble antioxidant capacity and constituting an additional risk factor for several clinical conditions. Given the emerging role of carotenoids in disease prevention, dietary advice on carotenoid-rich and fortified foods or the use of supplements in these patients should be considered.
C1 [Granado-Lorencio, F.; Herrero-Barbudo, C.; Blanco-Navarro, I.; Perez-Sacristan, B.] Hosp Univ Puerta de Hierro, Serv Bioquim Clin, Unidad Vitaminas, Madrid 28035, Spain.
   [Olmedilla-Alonso, B.] CSIC, Inst Frio, E-28040 Madrid, Spain.
C3 Hospital Puerta de Hierro-Majadahonda; Consejo Superior de
   Investigaciones Cientificas (CSIC)
RP Granado-Lorencio, F (通讯作者)，Hosp Univ Puerta de Hierro, Serv Bioquim Clin, Unidad Vitaminas, Madrid 28035, Spain.
EM fgranado.hpth@salud.madrid.org
RI Granado, Fernando/D-1048-2011; Olmedilla-Alonso, Begoña/D-1337-2012
OI Granado, Fernando/0000-0002-5561-7564; Olmedilla-Alonso,
   Begoña/0000-0002-4913-5171
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NR 21
TC 7
Z9 8
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0960-8923
EI 1708-0428
J9 OBES SURG
JI Obes. Surg.
PD JUL
PY 2009
VL 19
IS 7
BP 879
EP 882
DI 10.1007/s11695-008-9476-0
PG 4
WC Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Surgery
GA 466LP
UT WOS:000267664000011
PM 18369683
DA 2022-11-30
ER

PT J
AU Tang, JY
   Han, XY
   Tang, R
   Li, MY
   Wang, ZY
   Zhao, MW
   Qu, JF
AF Tang, Jiyang
   Han, Xinyao
   Tang, Ran
   Li, Mengyang
   Wang, Zongyi
   Zhao, Mingwei
   Qu, Jinfeng
TI Case series: pachychoroid pigment epitheliopathy transformed to
   polypoidal choroidal vasculopathy after long-term follow-up
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Pachychoroid; Pachychoroid pigment epitheliopathy; Polypoidal choroidal
   vasculopathy; Pachychoroid spectrum diseases
ID NEOVASCULARIZATION; ANGIOGRAPHY
AB Background Pachychoroid pigment epitheliopathy (PPE), a retinal disorder that falls into the pachychoroid spectrum, is characterized by retinal pigment epithelium changes in pachychoroid eyes without existing or previous subretinal fluid or soft drusen. Previous reports have indicated that PPE may share some pathophysiologic component with other pachychoroid spectrum diseases and could transform into central serous chorioretinopathy (CSC) during follow-up. CSC transformation to PNV and PCV has also been reported, but PPE transformation to PCV has not been reported. Case presentation Seven eyes of seven patients (four male three female, aged 62.7 +/- 8.4 years) who presented with PPE at baseline transformed to PCV during follow-up. All study eyes had baseline contralateral eye diagnoses of PCV. All PPE eyes reported no symptoms at baseline and were followed up regularly for the treatment of their contralateral eyes. All PPE presented as pigment epithelium detachment (PED) at baseline. The mean central macular thickness (CMT) was 217.6 +/- 14.6 mu m, the mean subfoveal choroidal thickness (SFCT) was 354.9 +/- 94.9 mu m, and the mean sub-PPE choroidal thickness was 332.3 +/- 84.6 mu m. The mean PPE width and height were 1326.4 +/- 791.4 mu m and 58.7 +/- 23.6 mu m, respectively, at baseline. Disruption of the ellipsoid zone (EZ) was noted in 3 eyes, while choroidal vascular hyperpermeability (CVH) was noted in 5 eyes at baseline. The follow-up period was 75.0 +/- 41.1 months, and the mean transformation time was 49.6 +/- 24.8 months. All study eyes received no intervention before transformation. Conclusions PPE could transform to PCV after a long follow-up period. Regular follow-ups for a long time should be recommended for patients with PPE.
C1 [Tang, Jiyang; Han, Xinyao; Tang, Ran; Li, Mengyang; Wang, Zongyi; Zhao, Mingwei; Qu, Jinfeng] Peking Univ Peoples Hosp, Dept Ophthalmol, 11 Xizhimen South St, Beijing 100044, Peoples R China.
   [Tang, Jiyang; Han, Xinyao; Tang, Ran; Li, Mengyang; Wang, Zongyi; Zhao, Mingwei; Qu, Jinfeng] Eye Dis & Optometry Inst, Beijing, Peoples R China.
   [Tang, Jiyang; Han, Xinyao; Tang, Ran; Li, Mengyang; Wang, Zongyi; Zhao, Mingwei; Qu, Jinfeng] Beijing Key Lab Diag & Therapy Retinal & Choroid, Beijing, Peoples R China.
   [Tang, Jiyang; Han, Xinyao; Tang, Ran; Li, Mengyang; Wang, Zongyi; Zhao, Mingwei; Qu, Jinfeng] Peking Univ, Hlth Sci Ctr, Coll Optometry, Beijing, Peoples R China.
C3 Peking University
RP Qu, JF (通讯作者)，Peking Univ Peoples Hosp, Dept Ophthalmol, 11 Xizhimen South St, Beijing 100044, Peoples R China.; Qu, JF (通讯作者)，Eye Dis & Optometry Inst, Beijing, Peoples R China.; Qu, JF (通讯作者)，Beijing Key Lab Diag & Therapy Retinal & Choroid, Beijing, Peoples R China.; Qu, JF (通讯作者)，Peking Univ, Hlth Sci Ctr, Coll Optometry, Beijing, Peoples R China.
EM qujinfeng_pkuph@126.com
OI Qu, Jinfeng/0000-0001-6875-8393
FU National Key R&D Program of China [2020YFC2008200]; Capital Clinical
   Diagnosis and Treatment Technology Research and Demonstration
   Application Project of China [Z191100006619029]
FX This study was supported by the National Key R&D Program of China (No.
   2020YFC2008200) and Capital Clinical Diagnosis and Treatment Technology
   Research and Demonstration Application Project of China (Grant:
   Z191100006619029). The funders had no role in the study design, data
   collection and analysis, decision to publish or preparation of the
   manuscript.
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NR 20
TC 0
Z9 0
U1 0
U2 0
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD JUN 21
PY 2022
VL 22
IS 1
AR 272
DI 10.1186/s12886-022-02487-8
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 2H4DO
UT WOS:000814247400002
PM 35729590
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Mazzeo, TJMM
   Leber, HM
   da Silva, AG
   Freire, RCM
   Barbosa, GCS
   Criado, GG
   Jacob, GAV
   Machado, CG
   Gomes, AMV
AF Mazzeo, Thiago Jose Muniz Machado
   Leber, Henrique Monteiro
   da Silva, Allan Gomes
   Freire, Raimunda Cristina Mendonca
   Barbosa, Gabriel Castilho Sandoval
   Criado, Guilherme Garcia
   Jacob, Gabriel Almeida Veiga
   Machado, Cleide Guimaraes
   Gomes, Andre Marcelo Vieira
TI Pachychoroid disease spectrum: review article
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Review
DE Pachychoroid; Multimodal retinal imaging; Anti-VEGF therapy;
   Photodynamic therapy; Central serous chorioretinopathy; Polypoidal
   choroidal vasculopathy
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; CENTRAL SEROUS CHORIORETINOPATHY;
   OPTICAL COHERENCE TOMOGRAPHY; VERTEPORFIN PHOTODYNAMIC THERAPY;
   INDOCYANINE GREEN ANGIOGRAPHY; MACULAR DEGENERATION; SWEPT-SOURCE;
   MICROPULSE PHOTOCOAGULATION; MINERALOCORTICOID RECEPTOR; FELLOW EYES
AB Purpose The aim of this article is to do a comprehensive literature review about the current understandings of the pachychoroid disease spectrum, describing its multimodal imaging analysis, pathophysiology, differential diagnosis, and current types of management.
   Methods This comprehensive literature review was performed based on a search on the PubMed database, of relevant pachychoroid published papers according to our current knowledge.
   Discussion The pachychoroid disease spectrum, according to some authors, includes the following: pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV)/aneurysmal type 1 neovascularization (AT1), and more recently focal choroidal excavation (FCE) and peripapillary pachychoroid syndrome (PPS). Each one of these entities will be described and discussed in this article.
   Conclusion Significant advances in multimodal imaging have enabled a better understanding of the typical choroidal changes in pachychoroid disease spectrum. The clinical knowledge and managing options about this disease significantly increased in the last years. However, it is still unclear why some eyes with typical pachychoroid disease phenotype show no evidence of RPE damage and subretinal fluid (uncomplicated pachychoroid) while others present progressive tissue damage, neovascularization, and atrophy.
C1 [Mazzeo, Thiago Jose Muniz Machado; Leber, Henrique Monteiro; da Silva, Allan Gomes; Freire, Raimunda Cristina Mendonca; Barbosa, Gabriel Castilho Sandoval; Jacob, Gabriel Almeida Veiga; Machado, Cleide Guimaraes; Gomes, Andre Marcelo Vieira] Suel Abujamra Inst, Retina & Vitreous Dept, Sao Paulo, Brazil.
   [Criado, Guilherme Garcia; Machado, Cleide Guimaraes] Univ Sao Paulo, Retina & Vitreous Dept, Sao Paulo, Brazil.
C3 Universidade de Sao Paulo
RP Mazzeo, TJMM (通讯作者)，Suel Abujamra Inst, Retina & Vitreous Dept, Sao Paulo, Brazil.
EM mazzeothiago@yahoo.com
RI Machado, Cleide Guimarães/GSM-6701-2022; Barbosa, Gabriel/HCH-8082-2022
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PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD MAR
PY 2022
VL 260
IS 3
BP 723
EP 735
DI 10.1007/s00417-021-05450-3
EA OCT 2021
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZB5IP
UT WOS:000707281300001
PM 34648069
DA 2022-11-30
ER

PT J
AU Lentzsch, A
   Schollhorn, L
   Schnorr, C
   Siggel, R
   Liakopoulos, S
AF Lentzsch, Anna
   Schoellhorn, Laura
   Schnorr, Christel
   Siggel, Robert
   Liakopoulos, Sandra
TI Comparison of swept-source versus spectral-domain optical coherence
   tomography angiography for detection of macular neovascularization
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Optical coherence tomography angiography; Macular neovascularization;
   Swept-source OCTA; Spectral-domain OCTA
ID OCT-ANGIOGRAPHY; CHOROIDAL NEOVASCULARIZATION; IMAGE ARTIFACTS;
   QUANTITATION
AB Purpose To compare swept-source (SS) versus spectral-domain (SD) optical coherence tomography angiography (OCTA) for the detection of macular neovascularization (MNV). Methods In this prospective cohort study, 72 eyes of 54 patients with subretinal hyperreflective material (SHRM) and/or pigment epithelial detachment (PED) on OCT possibly corresponding to MNV in at least one eye were included. OCTA scans were acquired using two devices, the PLEX Elite 9000 SS-OCTA and the Spectralis SD-OCTA. Fluorescein angiography (FA) was used as reference. Two graders independently evaluated en face OCTA images using a preset slab as well as a manually modified slab, followed by a combination of en face and cross-sectional OCTA. Results Sensitivity (specificity) for the automated slabs was 51.7% (93.0%) for SS-OCTA versus 58.6% (95.3%) for SD-OCTA. Manual modification of segmentation increased sensitivity to 79.3% for SS-OCTA but not for SD-OCTA (58.6%). The combination of en face OCTA with cross-sectional OCTA reached highest sensitivity values (SS-OCTA: 82.8%, SD-OCTA: 86.2%), and lowest number of cases with discrepancies between SS-OCTA and SD-OCTA (4.2%). Fleiss kappa as measure of concordance between FA, SS-OCTA, and SD-OCTA was 0.56 for the automated slabs, 0.60 for the manual slabs, and 0.73 (good agreement) for the combination of en face OCTA with cross-sectional OCTA. Concordance to FA was moderate for the automated slabs and good for manual slabs and combination with cross-sectional OCTA of both devices. Conclusion Both devices reached comparable results regarding the detection of MNV on OCTA. Sensitivity for MNV detection and agreement between devices was best when evaluating a combination of en face and cross-sectional OCTA.
C1 [Lentzsch, Anna; Schoellhorn, Laura; Schnorr, Christel; Siggel, Robert; Liakopoulos, Sandra] Cologne Image Reading Ctr, Fac Med, Dept Ophthalmol, Cologne, Germany.
   [Lentzsch, Anna; Schoellhorn, Laura; Schnorr, Christel; Siggel, Robert; Liakopoulos, Sandra] Univ Hosp Cologne, Cologne, Germany.
   [Siggel, Robert] Univ Witten Herdecke, Helios Univ Hosp Wuppertal, Dept Ophthalmol, Wuppertal, Germany.
   [Liakopoulos, Sandra] Goethe Univ, Dept Ophthalmol, Frankfurt, Germany.
C3 University of Cologne; University of Cologne; Witten Herdecke
   University; Goethe University Frankfurt
RP Liakopoulos, S (通讯作者)，Cologne Image Reading Ctr, Fac Med, Dept Ophthalmol, Cologne, Germany.; Liakopoulos, S (通讯作者)，Univ Hosp Cologne, Cologne, Germany.; Liakopoulos, S (通讯作者)，Goethe Univ, Dept Ophthalmol, Frankfurt, Germany.
EM Sandra.liakopoulos@uk-koeln.de
FU Projekt DEAL
FX Open Access funding enabled and organized by Projekt DEAL.
CR Al-Sheikh M, 2017, OSLI RETINA, V48, P385, DOI 10.3928/23258160-20170428-04
   Arya M, 2019, RETINA-J RET VIT DIS, V39, P1682, DOI 10.1097/IAE.0000000000002241
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   Zhang QQ, 2017, INVEST OPHTH VIS SCI, V58, P1506, DOI 10.1167/iovs.16-20977
NR 21
TC 0
Z9 0
U1 6
U2 12
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JAN
PY 2022
VL 260
IS 1
BP 113
EP 119
DI 10.1007/s00417-021-05229-6
EA JUL 2021
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YI0WK
UT WOS:000669753400001
PM 34226972
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Nakai, S
   Matsumiya, W
   Keiko, O
   Miki, A
   Nakamura, M
   Honda, S
AF Nakai, Shunichiro
   Matsumiya, Wataru
   Keiko, Otsuka
   Miki, Akiko
   Nakamura, Makoto
   Honda, Shigeru
TI The 24-month outcomes of intravitreal aflibercept combined with
   photodynamic therapy for polypoidal choroidal vasculopathy
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Aflibercept; Combination therapy; Polypoidal choroidal vasculopathy;
   PCV; Photodynamic therapy
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; COMBINATION THERAPY;
   RANIBIZUMAB; VERTEPORFIN; MONOTHERAPY; EFFICACY; SAFETY; VEGF
AB PurposeThis study was prospectively carried out to clarify the effectiveness of visual and anatomical outcomes under combination therapy of intravitreal aflibercept (IVA) and verteporfin photodynamic therapy (vPDT) in over 24months.Study designA single-arm prospective exploratory study.MethodsTwenty-six eyes of 26 treatment naive PCV patients were enrolled in this study. The primary outcome measures were the changes in best corrected visual acuity (BCVA) and the complete polyp regression rate. The secondary outcome measures included central retinal thickness assessed by optical coherence tomography.ResultsThe patients showed significant improvement in BCVA by 0.14 logMAR units at 12months and 0.11 logMAR units at 24months from baseline (both p<0.01). The mean central retinal thickness also significantly decreased at 12months (p<0.001) and at 24months (p=0.001). Complete regression of polypoidal lesions was achieved by 15 out of 20 eyes (75%) at 12months and 11 out of 20 eyes (55%) at 24months. The mean treatment number was 2.9 courses of IVA and 1.5 courses of vPDT and the mean retreatment free interval after initial therapy was 12.8months during follow up of 24months. The complete data from all predetermined examinations were observed in 17 out of 26 enrolled patients (65%) in this study.ConclusionIn this study, combination therapy of IVA and vPDT yielded visual and anatomical improvements in treatment-naive PCV patients over a 24-month follow-up period.
C1 [Nakai, Shunichiro; Matsumiya, Wataru; Keiko, Otsuka; Miki, Akiko; Nakamura, Makoto; Honda, Shigeru] Kobe Univ, Grad Sch Med, Dept Surg, Div Ophthalmol,Chuo Ku, 7-5-2 Kusunoki Cho, Kobe, Hyogo 6500017, Japan.
   [Honda, Shigeru] Osaka City Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Osaka, Japan.
C3 Kobe University; Osaka Metropolitan University
RP Matsumiya, W (通讯作者)，Kobe Univ, Grad Sch Med, Dept Surg, Div Ophthalmol,Chuo Ku, 7-5-2 Kusunoki Cho, Kobe, Hyogo 6500017, Japan.
EM ytkmatsu@hotmail.com
RI Honda, Shigeru/W-4761-2019
OI Nakamura, Makoto/0000-0002-6464-4302
FU Japan Society for the Promotion of Science (JSPS) KAKENHI [JP16K11286];
   JSPS KAKENHI [JP26861449]
FX This work was supported by Japan Society for the Promotion of Science
   (JSPS) KAKENHI Grant number JP16K11286 (S. Honda) and JSPS KAKENHI Grant
   number JP26861449 (W. Matsumiya)
CR Chan WM, 2004, OPHTHALMOLOGY, V111, P1576, DOI 10.1016/j.ophtha.2003.12.056
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NR 29
TC 6
Z9 6
U1 0
U2 2
PU SPRINGER JAPAN KK
PI TOKYO
PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065,
   JAPAN
SN 0021-5155
EI 1613-2246
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD JAN
PY 2019
VL 63
IS 1
BP 100
EP 108
DI 10.1007/s10384-018-0636-z
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HH0KB
UT WOS:000455404400012
PM 30406511
DA 2022-11-30
ER

PT J
AU Stone, LG
   Grinton, ME
   Talks, JS
AF Stone, Lydia G.
   Grinton, Michael E.
   Talks, James S.
TI Delayed follow-up of medical retina patients due to COVID-19: impact on
   disease activity and visual acuity
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Macular; Anti-VEGF; COVID-19; Visual acuity
ID DIABETIC MACULAR EDEMA; ANTI-VEGF; DEGENERATION
AB Purpose The coronavirus pandemic has prompted unprecedented delays to treatment with anti-VEGF intravitreal injections due to the need to reduce hospital attendances and prioritise the patients at highest risk of vision loss. This study aims to quantify the effect of these delays on visual acuity (VA) outcomes and optical coherence tomography (OCT) features for patients receiving treatment for neovascular age-related macular degeneration (nAMD), retinal vein occlusions (RVO) and diabetic macular oedema (DMO) and correlate to the Royal College of Ophthalmologists guidelines (RCOphth).
   Methods A retrospective data analysis of an electronic medical record was performed on a random sample of eyes receiving anti-VEGF injections for nAMD, RVO or DMO. Data collected included age, sex, reason for injection, number of weeks delay if > 8 weeks from that planned, VA at baseline and follow-up and the OCT features, if delayed. For those eyes not delayed, a visual acuity at 20 weeks was recorded to provide a control group.
   Results A sample of 981 eyes (858 patients) were analysed. There was a delay in review of 8 weeks or more in 39.6% of patients of which 30.4% had since returned for review (28.4% nAMD, 37.6% RVO and 30.0% DMO). There was no demographic difference identified between the delayed and non-delayed patients; however, the delayed group was significantly more likely to have better vision in their non-treated eye (p = 0.0003). A statistically significant difference was found in the change in VA between the delayed and the not-delayed group for eyes with nAMD (p = 0.001) but not for RVO or DMO. For the delayed group, mean CMT increased by 33 and 100 mu m, respectively, for nAMD and RVO and decreased by 7.8 mu m for DMO. The VA of 89.7% of DMO eyes returned to baseline, compared to 74.6% and 76.9% of nAMD and RVO eyes.
   Conclusion The RCOphth guidance to prioritise intravitreal injections for nAMD over DMO appears appropriate in this cohort but not for RVO. Eyes with nAMD experienced the greatest loss of vision with treatment delay, and nAMD and RVO eyes were less likely to return to baseline on restarting treatment.
C1 [Stone, Lydia G.; Grinton, Michael E.; Talks, James S.] Newcastle Tyne Hosp NHS Fdn Trust, Newcastle Eye Ctr, Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
C3 Newcastle University - UK; Newcastle Upon Tyne Hospitals NHS Foundation
   Trust
RP Stone, LG; Talks, JS (通讯作者)，Newcastle Tyne Hosp NHS Fdn Trust, Newcastle Eye Ctr, Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
EM Lydia.stone1@nhs.net; James.talks@nhs.net
OI Talks, James/0000-0001-6126-6476; Grinton, Michael/0000-0001-6284-774X;
   Stone, Lydia/0000-0003-3034-7809
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   Strata Decision Technology, 2020, EYEWIRE
   The Royal College of Ophthalmologists, 2020, MED RET MAN PLANS CO
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NR 21
TC 16
Z9 16
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUL
PY 2021
VL 259
IS 7
BP 1773
EP 1780
DI 10.1007/s00417-021-05174-4
EA MAY 2021
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA TI3LH
UT WOS:000649212700001
PM 33977317
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Rahman, F
   Zekite, A
   Bunce, C
   Jayaram, H
   Flanagan, D
AF Rahman, Farzana
   Zekite, Antra
   Bunce, Catey
   Jayaram, Hari
   Flanagan, Declan
TI Recent trends in vision impairment certifications in England and Wales
SO EYE
LA English
DT Article
AB Background The Certificate of Visual Impairment (CVI) provides essential data for preventable sight loss indicators as part of the Public Health Outcomes Framework (PHOF) published annually by the Department of Health. Trends in CVI certification rates can provide information on the effectiveness of current services and treatments and may be used to guide allocation of resources, and is the only such indicator within ophthalmology. This study aimed to compare recent trends in new vision impairment certifications in 2017/18 against prior baseline data in England and document trends in new certifications in Wales. Methods PHOF data from 2010/11 and 2017/18 were examined with respect to preventable sight loss indicators: age-related macular degeneration (AMD) (Indicator E12a), glaucoma (Indicator E12b), diabetic eye disease (Indicator E12c) as well as the total numbers of certifications (Indicator E12d). Results In 2017/18, the rate of new CVI certifications was 41 per 100,000 population which has reduced from 43/100,000 in 2010/11 in England. Certifications for AMD reduced from 132/100,000 in 2010/11 to 107/100,000 in 2017-18. Certifications for glaucoma have remained stable at 13/100,000 in 2017/8. Certifications for diabetic eye disease have declined from 4/100,000 in 2010/11 to 3/ 100,000 in 2017/18. The number of vision impaired individuals that each Clinical Commissioning Group (CCG) has to support varies from 8 to 82 per 100,000 population. Conclusions There has been a significant decrease in the rate of all CVI certifications particularly from AMD and diabetic retinopathy. However, maintaining this will require changes in the way care is delivered as the elderly population, which is at greatest risk of preventable sight loss, is projected to increase by 50% over the next 20 years. Inherited retinal diseases are now the leading cause of sight loss in the working age population. CVI data demonstrate the need for CCGs to tailor their investment in ophthalmic services to the needs of their specific patient populations. It is important that all ophthalmologists continue to provide accurate CVI data in order to help support the future equitable allocation of adequate resources to reduce avoidable vision loss.
C1 [Rahman, Farzana; Zekite, Antra; Jayaram, Hari; Flanagan, Declan] Moorfields Eye Hosp NHS Fdn Trust, London, England.
   [Zekite, Antra; Bunce, Catey; Jayaram, Hari] NIHR Moorfields Biomed Res Ctr, London, England.
   [Bunce, Catey] Kings Coll London, London, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; King's College London
RP Flanagan, D (通讯作者)，Moorfields Eye Hosp NHS Fdn Trust, London, England.
EM declan.flanagan1@nhs.net
RI Jayaram, Hari/H-7016-2019
OI Jayaram, Hari/0000-0003-1998-0670; Bunce, Catey/0000-0002-0935-3713
FU Moorfields Eye Charity; National Institute for Health Research
   Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital;
   UCL Institute of Ophthalmology
FX FR, AZ, HJ, and DF are employed by Moorfields Eye Hospital NHS
   Foundation Trust. HJ is supported by the Moorfields Eye Charity. AZ is
   supported by the National Institute for Health Research Biomedical
   Research Centre for Ophthalmology at Moorfields Eye Hospital and the UCL
   Institute of Ophthalmology. The data captured by the CVI and CVIW are
   the copyright of the Department of Health and Social Care and the Welsh
   Government respectively, and this work was made possible through a
   collaboration with the Royal College of Ophthalmologists. The views
   expressed in this paper are those of the authors and not necessarily
   those of any funding body or the Department of Health.
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NR 28
TC 23
Z9 23
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD JUL
PY 2020
VL 34
IS 7
BP 1271
EP 1278
DI 10.1038/s41433-020-0864-6
EA APR 2020
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MB5KN
UT WOS:000526991300005
PM 32291405
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Lores-Motta, L
   Paun, CC
   Corominas, J
   Pauper, M
   Geerlings, MJ
   Altay, L
   Schick, T
   Daha, MR
   Fauser, S
   Hoyng, CB
   den Hollander, AI
   de Jong, EK
AF Lores-Motta, Laura
   Paun, Constantin C.
   Corominas, Jordi
   Pauper, Marc
   Geerlings, Maartje J.
   Altay, Lebriz
   Schick, Tina
   Daha, Mohamed R.
   Fauser, Sascha
   Hoyng, Carel B.
   den Hollander, Anneke I.
   de Jong, Eiko K.
TI Genome-Wide Association Study Reveals Variants in CFH and CFHR4
   Associated with Systemic Complement Activation
SO OPHTHALMOLOGY
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; FACTOR-H; MACULAR DEGENERATION; ALTERNATIVE
   PATHWAY; GENETIC-VARIANTS; AGE; RESISTANCE; PROTEIN; CELLS; RISK
AB Purpose: To identify genetic variants associated with complement activation, which may help to select age-related macular degeneration (AMD) patients for complement-inhibiting therapies.
   Design: Genome-wide association study (GWAS) followed by replication and meta-analysis.
   Participants: AMD patients and controls (n = 2245).
   Methods: A GWAS on serum C3d-to-C3 ratio was performed in 1548 AMD patients and controls. For replication and meta-analysis, 697 additional individuals were genotyped. A model for complement activation including genetic and non-genetic factors was built, and the variance explained was estimated. Haplotype analysis was performed for 8 SNPs across the CFH/CFHR locus. Association with AMD was performed for the variants and haplotypes found to influence complement activation.
   Main Outcome Measures: Normalized C3d/C3 ratio as a measure of systemic complement activation.
   Results: Complement activation was associated independently with rs3753396 located in CFH (P-discovery 1.09 x 10(-15),; P-meta = 3.66 x 10(-2)1; p = 0.141; standard error [SE] = 0.015) and rs6685931 located in CFHR4 (P-discovery 8.18 x 10(-7),; P-meta= 6.32 x 10-8; p = 0.054; SE = 0.010). A model including age, AMD disease status, body mass index, triglycerides, rs3753396, rs6685931, and previously identified SNPs explained 18.7%of the variability in complement activation. Haplotype analysis revealed 3 haplotypes (H1-2 and H6 containing rs6685931 and H3 containing rs3753396) associated with complement activation. Haplotypes H3 and H6 conferred stronger effects on complement activation compared with the single variants (P = 2.53 x 10(-14); beta= 0.183; SE = 0.024; and P = 4.28 x 10(-4); beta = 0.144; SE = 0.041; respectively). Association analyses with AMD revealed that SNP rs6685931 and haplotype H1-2 containing rs6685931 were associated with a risk for AMD development, whereas SNP rs3753396 and haplotypes H3 and H6 were not.
   Conclusions: The SNP rs3753396 in CFH and SNP rs6685931 in CFHR4 are associated with systemic complement activation levels. The SNP rs6685931 in CFHR4 and its linked haplotype H1-2 also conferred a risk for AMD development, and therefore could be used to identify AMD patients who would benefit most from complement-inhibiting therapies. (C) 2018 by the American Academy of Ophthalmology.
C1 [Lores-Motta, Laura; Paun, Constantin C.; Corominas, Jordi; Pauper, Marc; Geerlings, Maartje J.; Hoyng, Carel B.; den Hollander, Anneke I.; de Jong, Eiko K.] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.
   [Corominas, Jordi; Pauper, Marc; den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.
   [Altay, Lebriz; Schick, Tina; Fauser, Sascha] Univ Hosp Cologne, Dept Ophthalmol, Cologne, Germany.
   [Daha, Mohamed R.] Leiden Univ, Dept Nephrol, Med Ctr, Leiden, Netherlands.
   [Fauser, Sascha] F Hoffmann La Roche Ltd, Roche Pharma Res & Early Dev, Basel, Switzerland.
C3 Radboud University Nijmegen; Radboud University Nijmegen; University of
   Cologne; Leiden University; Leiden University Medical Center (LUMC);
   Leiden University - Excl LUMC; Roche Holding
RP de Jong, EK (通讯作者)，Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, Route 409,Philips van Leydenlaan 15, NL-6525 EX Nijmegen, Netherlands.
EM Eiko.deJong@radboudumc.nl
RI Pauper, Marc/B-6342-2018; Geerlings, Maartje/P-3338-2019; Pauper,
   Marc/AGZ-0438-2022; Hollander, Anneke den/N-4911-2014
OI Pauper, Marc/0000-0001-6274-9891; Geerlings,
   Maartje/0000-0003-1164-3573; Pauper, Marc/0000-0001-6274-9891;
   Lores-Motta, Laura/0000-0002-2423-9126
FU European Research Council (the European Union's Seventh Framework
   Programme [FP]/European Research Council grant) [310644]; European
   Union's Horizon 2020 research and innovation programme/European Research
   Council [737607]; Foundation Fighting Blindness, Columbia, Maryland
   [C-GE-0811-0548-RAD04]; Stichting A. F. Deutman Oogheelkunde
   Researchfonds Nijmegen (Nijmegen, Gelderland, The Netherlands); National
   Institutes of Health, Bethesda, Maryland [R01 EY022310]; NATIONAL EYE
   INSTITUTE [R01EY022310] Funding Source: NIH RePORTER
FX Supported by: the European Research Council (the European Union's
   Seventh Framework Programme [FP/2007-2013]/European Research Council
   grant agreement no. 310644 [MACULA]; the European Union's Horizon 2020
   research and innovation programme/European Research Council grant
   agreement no. 737607 [MACULA2]); Foundation Fighting Blindness,
   Columbia, Maryland (center grant no.: C-GE-0811-0548-RAD04 to Radboud
   University Medical Center); and the Stichting A. F. Deutman Oogheelkunde
   Researchfonds Nijmegen (Nijmegen, Gelderland, The Netherlands). The
   sponsor or funding organization had no role in the design or conduct of
   this research. The authors acknowledge the contribution of the
   International AMD Genomics Consortium, supported by the National
   Institutes of Health, Bethesda, Maryland (grant no.: R01 EY022310).
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NR 53
TC 43
Z9 43
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2018
VL 125
IS 7
BP 1064
EP 1074
DI 10.1016/j.ophtha.2017.12.023
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GL0DD
UT WOS:000436632700025
PM 29398083
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Muller, S
   Ehlken, C
   Bauer-Steinhusen, U
   Lechtenfeld, W
   Hasanbasic, Z
   Agostini, H
   Wilke, T
AF Mueller, S.
   Ehlken, C.
   Bauer-Steinhusen, U.
   Lechtenfeld, W.
   Hasanbasic, Z.
   Agostini, H.
   Wilke, T.
TI Treatment of age-related neovascular macular degeneration: the patient's
   perspective
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Neovascular age-related macular degeneration; Anti-VEGF therapy; Patient
   perspective; Prospective non-interventional cohort study; Germany
ID RANIBIZUMAB TREATMENT; ADHERENCE
AB The aim of this study was to assess patients' views and expectations with regard to neovascular age-related macular degeneration (nAMD) and intravitreal anti-VEGF therapy (IVT).
   We conducted a multicenter, non-interventional, prospective cohort study including nAMD patients treated with IVT in Germany. Patients with at least one IVT before study enrollment and aged ae<yen>50 years were included. Three telephone interviews were conducted during a 12-month observational period. Here, patient's beliefs/expectations with regard to the nAMD disease and the IVT treatment were discussed. Only patients who completed all three phone interviews were included in the analyses. We used a two-step cluster analysis to identify patient clusters regarding specific patient attitudes towards nAMD and its treatment.
   Three hundred and thirty-two patients completed all interviews (mean age of 76.4 +/- 7.2 years, 59.0% women). Out of these, 57.8% acknowledged that they needed general assistance in daily life, while 77.4% stated being able to attend general medical appointments on their own. However, 64.7% needed a driver or an accompanying person to attend their IVT appointments.
   In addition, 3.9% of the patients were afraid of IVT side effects. Also, 87.3% and 43.1% of the patients could name their disease or the anti-VEGF drug administered, respectively. More than three-quarters of the patients (83.1%) were aware of possible consequences of nAMD by stating vision loss or blindness, but only 16.6% knew that nAMD is a chronic disease.
   Generally, patients were optimistic: 70.2%, 5.1% and 13.0% of them expected stable visual acuity (VA), a significant improvement or expected worsening of VA in the next year, respectively. Almost two thirds of patients who provided their therapy expectations (47.0%) anticipated fewer injections/discontinuation of IVT.
   We identified five patient clusters differing significantly from each other with regard to four variables: being afraid of IVT, nAMD disease awareness, optimism with regard to effectiveness of IVT, and nAMD disease and treatment knowledge.
   Only a minority of patients is aware of the chronic nature of nAMD. To motivate patients to accept a life-long IVT treatment, physicians and caregivers must know that there exist different patient types with significant differences in communication needs.
C1 [Mueller, S.; Wilke, T.] Univ Wismar, IPAM Inst Pharmacoecon & Medicat Logist, Alter Holzhafen 19, D-23966 Wismar, Germany.
   [Ehlken, C.] Univ Klinikum Schleswig Holstein, Dept Ophthalmol, Campus Kiel, Germany.
   [Bauer-Steinhusen, U.; Hasanbasic, Z.] Bayer Vital GmbH, Med Affairs, Kaiser Wilhelm Allee 70, D-51373 Leverkusen, Germany.
   [Lechtenfeld, W.] PRO RETINA Deutschland eV, Vaalser Str 108, D-52074 Aachen, Germany.
   [Agostini, H.] Univ Freiburg, Ctr Eye, Med Ctr, Fac Med, Killianstr 5, D-79106 Freiburg, Germany.
C3 University of Kiel; Schleswig Holstein University Hospital; Bayer AG;
   University of Freiburg
RP Muller, S (通讯作者)，Univ Wismar, IPAM Inst Pharmacoecon & Medicat Logist, Alter Holzhafen 19, D-23966 Wismar, Germany.
EM kontakt@ipam-wismar.de
FU Bayer vital GmbH, Leverkusen, Germany
FX The study was funded by Bayer vital GmbH, Leverkusen, Germany.
CR Bezreh T, 2012, PATIENT PREFER ADHER, V6, P11, DOI 10.2147/PPA.S25971
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NR 20
TC 19
Z9 19
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD NOV
PY 2017
VL 255
IS 11
BP 2237
EP 2246
DI 10.1007/s00417-017-3739-1
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FJ8HR
UT WOS:000413006000018
PM 28776095
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Parmeggiani, F
   Costagliola, C
   Semeraro, F
   Romano, MR
   Rinaldi, M
   Gallenga, CE
   Serino, ML
   Incorvaia, C
   D'Angelo, S
   De Nadai, K
   Dell'Omo, R
   Russo, A
   Gemmati, D
   Perri, P
AF Parmeggiani, Francesco
   Costagliola, Ciro
   Semeraro, Francesco
   Romano, Mario R.
   Rinaldi, Michele
   Gallenga, Carla Enrica
   Serino, Maria Luisa
   Incorvaia, Carlo
   D'Angelo, Sergio
   De Nadai, Katia
   Dell'Omo, Roberto
   Russo, Andrea
   Gemmati, Donato
   Perri, Paolo
TI Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after
   Photodynamic Therapy for Neovascular Macular Degeneration
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE macular degenerations; choroidal neovascularization; pharmacogenetics;
   photodynamic therapy with verteporfin; fibrin-clot stability; factor
   XIII-A G185T gene polymorphism; anti-thrombophilia
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; COAGULATION-FACTOR XIII;
   PATHOLOGICAL MYOPIA; VERTEPORFIN THERAPY; FIBRIN STRUCTURE; INTRAVITREAL
   BEVACIZUMAB; RANIBIZUMAB MONOTHERAPY; PREDICTIVE ROLE; CLOT FORMATION;
   LESION SIZE
AB Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD) and pathologic myopia (PM), both of which are frequently complicated by subfoveal choroidal neovascularization (CNV). Photodynamic therapy with verteporfin (PDT-V) is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985) has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1) total number of photodynamic treatments; and (2) change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype) received a higher number of photodynamic treatments than patients without it (GG wild-type genotype) (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively). Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively). The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of both anti-thrombophilic effects due to FXIII-A G185T variant and photo-thrombotic action of PDT-V toward CNV provides several clues about the rationale of this intriguing pharmacogenetic correlation. Further investigations are warranted to outline the appropriate paradigm for guiding PDT-V utilization in the course of the combined therapeutic protocol for neovascular macular degeneration.
C1 [Parmeggiani, Francesco; Gallenga, Carla Enrica; Incorvaia, Carlo; D'Angelo, Sergio; De Nadai, Katia; Perri, Paolo] Univ Ferrara, Dept Biomed & Specialty Surg Sci, Eye Clin, I-44124 Cona Ferrara, Italy.
   [Costagliola, Ciro; Dell'Omo, Roberto] Univ Molise, Dept Hlth Sci, Eye Clin, I-86100 Campobasso, Italy.
   [Semeraro, Francesco; Russo, Andrea] Univ Brescia, Dept Neurol & Vis Sci, Eye Clin, I-25123 Brescia, Italy.
   [Romano, Mario R.] Univ Naples Federico II, Dept Neurosci Reprod & Odontostomatol Sci, Eye Clin, I-80131 Naples, Italy.
   [Rinaldi, Michele] Univ Naples 2, Dept Ophthalmol, I-80131 Naples, Italy.
   [Serino, Maria Luisa; Gemmati, Donato] Univ Ferrara, Ctr Thrombosis & Hemostasis, Dept Med Sci, I-44121 Ferrara, Italy.
C3 University of Ferrara; University of Molise; University of Brescia;
   University of Naples Federico II; Universita della Campania Vanvitelli;
   University of Ferrara
RP Parmeggiani, F (通讯作者)，Univ Ferrara, Dept Biomed & Specialty Surg Sci, Eye Clin, Via Aldo Moro 8, I-44124 Cona Ferrara, Italy.
EM prmfnc@unife.it; ciro.costagliola@unimol.it;
   francesco.semeraro@unibs.it; mario.romano4@unina.it;
   michele.rinaldi@unina2.it; gllcln@unife.it; srnmls@unife.it;
   ncrcrl@unife.it; das@unife.it; katia.denadai@libero.it;
   robdellomo@libero.it; dott.andrea.russo@gmail.com; cet@unife.it;
   prrpla@unife.it
RI Serino, Maria Luisa/AAC-7368-2022; dell'Omo, Roberto/K-7328-2016;
   Costagliola, Ciro/G-5707-2012; Semeraro, Francesco fs/K-8667-2016;
   Perri, Paolo/L-3047-2015
OI dell'Omo, Roberto/0000-0002-7663-8874; Costagliola,
   Ciro/0000-0001-8477-6188; Semeraro, Francesco fs/0000-0002-2275-4917;
   D'Angelo, Sergio/0000-0003-1118-3845; Perri, Paolo/0000-0003-4652-9842;
   Gallenga, Carla Enrica/0000-0002-7426-8603; Gemmati,
   Donato/0000-0001-6213-6120
FU Program of Scientific Research of Relevant National Interest; Ministry
   of Education University and Research of Italy [PRIN-2009NZAZSJ]
FX This study was supported by the Program of Scientific Research of
   Relevant National Interest co-financed by the Ministry of Education
   University and Research of Italy (PRIN-2009NZAZSJ).
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NR 81
TC 7
Z9 7
U1 0
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD AUG
PY 2015
VL 16
IS 8
BP 19796
EP 19811
DI 10.3390/ijms160819796
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA CZ0WE
UT WOS:000366826100164
PM 26307969
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Saeki, K
   Obayashi, K
   Nishi, T
   Miyata, K
   Maruoka, S
   Ueda, T
   Okamoto, M
   Hasegawa, T
   Matsuura, T
   Tone, N
   Ogata, N
   Kurumatani, N
AF Saeki, Keigo
   Obayashi, Kenji
   Nishi, Tomo
   Miyata, Kimie
   Maruoka, Shinji
   Ueda, Tetsuo
   Okamoto, Masahiro
   Hasegawa, Taiji
   Matsuura, Toyoaki
   Tone, Nobuhiro
   Ogata, Nahoko
   Kurumatani, Norio
TI Short-term influence of cataract surgery on circadian biological rhythm
   and related health outcomes (CLOCK-IOL trial): study protocol for a
   randomized controlled trial
SO TRIALS
LA English
DT Article
DE Cataract surgery; Circadian rhythm; Depression; Sleep disturbance;
   Diabetes mellitus
ID GERIATRIC DEPRESSION SCALE; URINARY MELATONIN EXCRETION; BLOCKING
   INTRAOCULAR-LENS; CROSS-SECTIONAL ANALYSIS; SHIFT WORK; BRIGHT LIGHT;
   BLUE-LIGHT; COGNITIVE IMPAIRMENT; SKIN TEMPERATURE; GANGLION-CELLS
AB Background: Light information is the most important cue of circadian rhythm which synchronizes biological rhythm with external environment. Circadian misalignment of biological rhythm and external environment is associated with increased risk of depression, insomnia, obesity, diabetes, cardiovascular disease, and cancer. Increased light transmission by cataract surgery may improve circadian misalignment and related health outcomes. Although some observational studies have shown improvement of depression and insomnia after cataract surgery, randomized controlled trials are lacking. We will conduct a parallel-group, assessor-blinded, simple randomized controlled study comparing a cataract surgery group at three months after surgery with a control group to determine whether cataract surgery improves depressive symptoms, sleep quality, body mass regulation, and glucose and lipid metabolism.
   Methods/Design: We will recruit patients who are aged 60 years and over, scheduled to receive their first cataract surgery, and have grade 2 or higher nuclear opacification as defined by the lens opacities classification system III. Exclusion criteria will be patients with major depression, severe corneal opacity, severe glaucoma, vitreous haemorrhage, proliferative diabetic retinopathy, macular oedema, age-related macular degeneration, and patients needing immediate or combined cataract surgery. After baseline participants will be randomized to two groups. Outcomes will be measured at three months after surgery among the intervention group, and three months after baseline among the control group. We will assess depressive symptoms as a primary outcome, using the short version geriatric depression scale (GDS-15). Secondary outcomes will be subjective and actigraph-measured sleep quality, sleepiness, glycated haemoglobin, fasting plasma glucose and triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, body mass index, abdominal circumference, circadian rhythms of physical activity and wrist skin temperature, and urinary melatonin metabolite. Chronotype and visual function will be assessed using the 'morningness-eveningness' questionnaire, the Munich chronotype questionnaire, and the National Eye Institute Visual Function Questionnaire.
   Discussion: Although there are potential limitations due to the difference in duration from baseline survey to outcome measurements between two groups, any seasonal effect on the outcome measurement will be balanced as a result of continuous inclusion of participants through the year, and outcomes will be adjusted for day length at outcome measurements at analysis.
C1 [Saeki, Keigo; Obayashi, Kenji; Kurumatani, Norio] Nara Med Univ, Sch Med, Dept Epidemiol & Community Hlth, Kashiharashi, Nara 6348521, Japan.
   [Nishi, Tomo; Miyata, Kimie; Maruoka, Shinji; Ueda, Tetsuo; Okamoto, Masahiro; Hasegawa, Taiji; Matsuura, Toyoaki; Ogata, Nahoko] Nara Med Univ, Sch Med, Dept Ophthalmol, Kashiharashi, Nara 6348521, Japan.
   [Tone, Nobuhiro] Nara Med Univ, Sch Med, Ctr Acad Ind & Govt Relat, Kashiharashi, Nara 6348521, Japan.
RP Saeki, K (通讯作者)，Nara Med Univ, Sch Med, Dept Epidemiol & Community Hlth, 840 Shijocho, Kashiharashi, Nara 6348521, Japan.
EM saekik@naramed-u.ac.jp
RI SAEKI, KEIGO/GWU-5723-2022; Hasegawa, Taiji/ABG-8260-2021
FU Nara Medical University; Grants-in-Aid for Scientific Research
   [24592637] Funding Source: KAKEN
FX The present study is supported by a grant for collaboration study from
   Nara Medical University.
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NR 71
TC 5
Z9 5
U1 1
U2 39
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1745-6215
J9 TRIALS
JI Trials
PD DEC 29
PY 2014
VL 15
AR 514
DI 10.1186/1745-6215-15-514
PG 8
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA AY4SM
UT WOS:000347568400001
PM 25547247
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kumagai, K
   Hangai, M
   Larson, E
   Ogino, N
AF Kumagai, Kazuyuki
   Hangai, Masanori
   Larson, Eric
   Ogino, Nobuchika
TI Vitreoretinal Interface and Foveal Deformation in Asymptomatic Fellow
   Eyes of Patients with Unilateral Macular Holes
SO OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL-COHERENCE-TOMOGRAPHY; POSTERIOR VITREOUS DETACHMENT; ATTACHMENT
AB Purpose: To compare the vitreoretinal interface of the asymptomatic fellow eyes of patients with unilateral macular holes (MHs) with that of the asymptomatic fellow eyes of patients with other retinal diseases and with that of healthy eyes.
   Design: Retrospective, observational cross-sectional study.
   Participants: This study included 137 healthy volunteers and 929 eyes of 929 patients with various unilateral retinal diseases.
   Methods: We reviewed medical charts, fundus photographs, and spectral-domain optical coherence tomographic (SD OCT) images. The incidence of the features of the vitreoretinal interface and foveal structures in the SD OCT images were compared among the asymptomatic fellow eyes of patients with unilateral MHs (n = 242), age-related macular degeneration (n = 129), epiretinal membrane (n = 185), macular pseudohole (n = 48), rhegmatogenous retinal detachment (n = 68), retinal vein occlusion (n = 257), and 1 of the eyes of healthy individuals (n = 137).
   Main Outcome Measures: Findings of slit-lamp biomicroscopy and SD OCT B-scan images.
   Results: The SD OCT B-scan images showed different types of foveal deformations associated with vitreofoveal adhesions in eyes without a posterior vitreous detachment (PVD) in the macular area. The incidence of the foveal deformations associated with vitreofoveal adhesions was significantly higher (P<0.0001) in the fellow eyes of the unilateral MH group (17%) than that in the other groups (0%-2%), except for the macular pseudohole group (8%). The SD OCT B-scan images also showed residual foveal deformations in eyes with a macular PVD. The incidence of a residual foveal deformation in eyes with a macular PVD was significantly higher (P<0.0001) in the MH group (32%) than that in any other group (0%-9%).
   Conclusions: The higher incidence of foveal deformations in the fellow eyes of patients with unilateral MHs with and without vitreofoveal adhesions suggests that patients in whom MHs develop have abnormally strong vitreofoveal adhesions sufficient to cause foveal deformation.
   Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011; 118: 1638-1644 (C) 2011 by the American Academy of Ophthalmology.
C1 [Kumagai, Kazuyuki; Ogino, Nobuchika] Shinjo Ophthalmol Inst, Miyazaki 8800035, Japan.
   [Hangai, Masanori] Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto, Japan.
   [Larson, Eric] Miyazaki Prefectural Nursing Univ, Miyazaki, Japan.
C3 Kyoto University
RP Kumagai, K (通讯作者)，Shinjo Ophthalmol Inst, 889-1 Mego Shimokitakata Machi, Miyazaki 8800035, Japan.
EM ganka@kamiiida-hp.jp
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NR 27
TC 24
Z9 25
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD AUG
PY 2011
VL 118
IS 8
BP 1638
EP 1644
DI 10.1016/j.ophtha.2011.01.022
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800TT
UT WOS:000293390900022
PM 21459450
DA 2022-11-30
ER

PT J
AU Yang, P
   Wiser, JL
   Peairs, JJ
   Ebright, JN
   Zavodni, ZJ
   Rickman, CB
   Jaffe, GJ
AF Yang, P
   Wiser, JL
   Peairs, JJ
   Ebright, JN
   Zavodni, ZJ
   Rickman, CB
   Jaffe, GJ
TI Human RPE expression of cell survival factors
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID NF-KAPPA-B; ALPHA-INDUCED APOPTOSIS; PIGMENT EPITHELIAL-CELLS;
   NECROSIS-FACTOR-ALPHA; CHOROIDAL NEOVASCULAR MEMBRANES; MACULAR
   DEGENERATION; TNF-ALPHA; PROLIFERATIVE VITREORETINOPATHY;
   DIABETIC-RETINOPATHY; EPIRETINAL MEMBRANES
AB PURPOSE. To determine basal and tumor necrosis factor (TNF)-alpha-regulated expression of retinal pigment epithelial (RPE) cell survival factors and whether regulation is dependent on nuclear transcription factor (NF)-kappa B.
   METHODS. Cultured human RPE cells were infected with adenovirus encoding either mutant inhibitory (I)-kappa B or beta-galactosidase and treated with TNF-alpha for various times. Freshly prepared RPE/choroid and RPE samples were isolated from human donor eyes. Real-time reverse transcription-polymerase chain reaction, Western blot, and immunocytochemistry were used to determine survival factor gene expression, cellular protein levels, and localization, respectively.
   RESULTS. Multiple survival factor genes, including cellular inhibitor of apoptosis protein (c-IAP1), c-IAP2, TNF receptor-associated factor-1 (TRAF-1), TRAF-2, B-cell leukemia/lymphoma-2 (Bcl-2), Bcl-x, A1, and cellular Fas-associated death domain (FADD)-like interleukin-1 beta-converting enzyme-like inhibitory protein (c-FLIP), were expressed in basal conditions in both cultured RPE cells and RPE cells in situ, whereas survivin was expressed only by cultured cells. TNF-alpha upregulated expression of TRAF-1, TRAF-2, c-IAP1, c-IAP2, c-FLIP, and A1. TRAF-1, c-FLIP, and to a lesser extent c-IAP2 protein levels were increased by TNF-alpha in a time-dependent manner, whereas c-IAP1, survivin, Bcl-x(L), and TRAF-2 protein levels were not influenced by TNF-alpha treatment at any time point tested. In contrast, Bcl-2 and A1 proteins were not detected under basal conditions or after TNF-alpha treatment. Overexpression of mutant I kappa B blocked TNF-alpha-induced TRAF-1, TRAF-2, c-IAP1, c-IAP2, c-FLIP, and A1 gene expression and downregulated TRAF-1 protein levels. TRAF-1 and Bcl-x L proteins were localized diffusely in RPE cytoplasm.
   CONCLUSIONS. Multiple RPE cell survival factors are expressed by human RPE cells. TNF-alpha regulates expression of some of these factors in an NF-kappa B- dependent manner, whereas others are not influenced by NF-kappa B. RPE cell survival factors may protect RPE cells from apoptosis normally and in diseases such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR).
C1 Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
   Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
C3 Duke University; Duke University
RP Jaffe, GJ (通讯作者)，Duke Univ, Ctr Eye, Dept Ophthalmol, Box 3802, Durham, NC 27710 USA.
EM jaffe001@mc.duke.edu
OI Bowes Rickman, Catherine/0000-0002-8555-9596
FU NEI NIH HHS [P30 EY 05722, R01 EY 11286, R01 EY 9106, R01 EY011286]
   Funding Source: Medline; NATIONAL EYE INSTITUTE [R01EY011286,
   R01EY009106, P30EY005722] Funding Source: NIH RePORTER
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NR 55
TC 30
Z9 33
U1 0
U2 7
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2005
VL 46
IS 5
BP 1755
EP 1764
DI 10.1167/iovs.04-1039
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 920RO
UT WOS:000228708000033
PM 15851579
DA 2022-11-30
ER

PT J
AU Foot, B
   Foy, R
   Chakravarthy, U
   Wormald, R
AF Foot, B
   Foy, R
   Chakravarthy, U
   Wormald, R
TI Increasing use of a new health technology during the wait for NICE
   guidance: findings from the third national tracker survey of
   photodynamic therapy
SO JOURNAL OF PUBLIC HEALTH
LA English
DT Article
DE photodynamic therapy; service provision; health technology
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION;
   VERTEPORFIN
AB Background Photodynamic therapy (PDT) is a relatively new treatment for neovascular age-related macular degeneration. Trial evidence suggests that repeated treatments with PDT can decrease the relative risk of a reduction in visual acuity over 2 years. Concerns raised over the clinical and cost effectiveness of the treatment prompted a technology appraisal by the National Institute for Clinical Effectiveness ( NICE). Difficulties in assessing the possible benefit or otherwise of PDT have led to delays in the publication of guidance. During this time the introduction of PDT into the UK National Health Service ( NHS) has continued. Over three annual tracker surveys, we describe trends in the provision of PDT in the NHS and potential difficulties in the implementation of NICE guidance.
   Methods We undertook surveys in each October of 2000, 2001 and 2002 of clinical directors or lead consultants in all NHS eye units. These sought data on which ( if any) patients were referred or treated with PDT and the thresholds of support for the use of PDT.
   Results Response rates were 82 per cent, 79 per cent and 82 per cent. The proportion of units routinely providing PDT for patients with more than 50 per cent classic sub-foveal CNV increased from 8.5 per cent in 2000 to 31 per cent in 2002 ( p < 0.001). Units referring or treating no patients decreased from 35 per cent to 10 per cent between 2000 and 2002 ( p < 0.001). There was a significant fall in the proportion of units changing policies on provision between 2000 - 2001 and 2001 - 2002. The proportion of respondents requiring further evidence before supporting the use of PDT decreased from 33 per cent in 2000 to 20 per cent in 2002.
   Conclusions There is evidence of a continuing growth in access to PDT in the absence of NICE guidance. Although 90 per cent of units offer some pathway to treatment important variations in reported provision remain. Given that PDT services are becoming established, there is a risk that clinical policy is determined by local service development as much as by national guidance.
C1 Royal Coll Ophthalmologists, London, England.
   Moorfields Eye Hosp, Dept Res & Dev, London EC1V 2PD, England.
   Univ Newcastle, Ctr Hlth Serv Res, Newcastle, NSW 2308, Australia.
   Queens Univ Belfast, Belfast, Antrim, North Ireland.
   Royal Victoria Hosp, Belfast BT12 6BA, Antrim, North Ireland.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of Newcastle; Queens University Belfast
RP Foot, B (通讯作者)，Royal Coll Ophthalmologists, London, England.
EM barny.foot@moorfields.nhs.uk
OI Foy, Robbie/0000-0003-0605-7713; Chakravarthy, Usha/0000-0002-2606-3734
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   WORMALD R, 2001, COCHRANE LIB, P1
   NHS DELAYS CAUSING B
NR 13
TC 3
Z9 3
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1741-3842
J9 J PUBLIC HEALTH
JI J. Public Health
PD MAR
PY 2004
VL 26
IS 1
BP 52
EP 55
DI 10.1093/pubmed/fdh112
PG 4
WC Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Public, Environmental & Occupational Health
GA 829IC
UT WOS:000222040100013
PM 15044575
OA Bronze
DA 2022-11-30
ER

PT J
AU Alge, CS
   Priglinger, SG
   Neubauer, AS
   Kampik, A
   Zillig, M
   Bloemendal, H
   Welge-Lussen, U
AF Alge, CS
   Priglinger, SG
   Neubauer, AS
   Kampik, A
   Zillig, M
   Bloemendal, H
   Welge-Lussen, U
TI Retinal pigment epithelium is protected against apoptosis by alpha
   B-crystallin
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID HEAT-SHOCK PROTEINS; LIGHT-INDUCED APOPTOSIS; GROWTH-FACTOR-BETA;
   MACULAR DEGENERATION; CELL-DEATH; ANTIOXIDANT ENZYMES; CYTOCHROME-C;
   NEGATIVE REGULATION; MULTIPLE-SCLEROSIS; APAF-1 APOPTOSOME
AB PURPOSE. The degeneration of retinal pigment epithelial (RPE) cells is considered to be a crucial event in the pathophysiology of age-related macular degeneration (AMD). Cumulative oxidative damage has been implicated in the development of the changes seen in AMD. The present study was undertaken to evaluate the expression of the small heat shock protein alphaB-crystallin in the RPE in response to oxidative stress and to explore whether alphaB-crystallin expression confers an antiapoptotic cytoprotective effect on RPE cells.
   METHODS. Native human RPE cells from the macula and retinal periphery were analyzed by RT-PCR and Western blot analysis for expression of alphaB-crystallin. Monolayer cultures of human RPE cells were stressed by heat shock (42degreesC for 20 minutes) or oxidant-mediated injury (50-300 muM H2O2 for 1 hour). Induction of alphaB-crystallin and the corresponding mRNA was assessed by Western and Northern blot analyses. To study the cytoprotective effect of alphaB-crystallin, human RPE cells were transfected with either a neomycin-selectable expression vector containing alphaB-crystallin cDNA or a control vector without alphaB-crystallin cDNA. Caspase-3 activity was determined by observing the cleavage of a colorimetric peptide substrate. Cell viability was quantified by combined propidium, iodide and Hoechst 33342 staining.
   RESULTS. alphaB-crystallin is constitutively expressed in RPE under in vivo and in vitro conditions. Western blot analysis of freshly isolated RPE showed greater baseline expression levels in RPE derived from the macular area than in that from the more peripheral regions. Heat shock treatment and oxidative stress caused a significant increase in alphaB-crystallin mRNA and protein. Oxidant-mediated injury in RPE cells with baseline expression levels of alphaB-crystallin resulted in apoptotic cell death, as measured by caspase-3 activity, whereas RPE cells that had been stably transfected with alphaB-crystallin were more resistant to H2O2-induced cellular injury.
   CONCLUSIONS. alphaB-crystallin may function as a stress-inducible antiapoptotic protein in human RPE and is inducible by oxidative stress, a condition implicated in the pathogenesis of AMD. Overexpression of alphaB-crystallin may be an important mechanism for the RPE to prevent apoptotic cell death in response to cellular stress.
C1 Univ Munich, Dept Ophthalmol, D-80336 Munich, Germany.
   Univ Erlangen Nurnberg, Dept Anat 2, Erlangen, Germany.
   Univ Nijmegen, Dept Biochem, Nijmegen, Netherlands.
C3 University of Munich; University of Erlangen Nuremberg; Radboud
   University Nijmegen
RP Welge-Lussen, U (通讯作者)，Univ Munich, Dept Ophthalmol, Mathildenstr 8, D-80336 Munich, Germany.
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NR 58
TC 122
Z9 137
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2002
VL 43
IS 11
BP 3575
EP 3582
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 609AB
UT WOS:000178879500028
PM 12407170
DA 2022-11-30
ER

PT J
AU Plank, T
   Benkowitsch, EMA
   Beer, AL
   Brandl, S
   Malania, M
   Frank, SM
   Jagle, H
   Greenlee, MW
AF Plank, Tina
   Benkowitsch, Edith M. A.
   Beer, Anton L.
   Brandl, Sabine
   Malania, Maka
   Frank, Sebastian M.
   Jaegle, Herbert
   Greenlee, Mark W.
TI Cortical Thickness Related to Compensatory Viewing Strategies in
   Patients With Macular Degeneration
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE macular degeneration; central vision loss; cortical thickness (CT);
   visual cortex; cortical eye fields; magnetic resonance imaging (MRI)
ID SACCADIC EYE-MOVEMENTS; PREFERRED RETINAL LOCUS; VISUAL MEMORY; FIELD;
   CORTEX; FMRI; ACTIVATION; PURSUIT; HUMANS; INHIBITION
AB Retinal diseases like age-related macular degeneration (AMD) or hereditary juvenile macular dystrophies (JMD) lead to a loss of central vision. Many patients compensate for this loss with a pseudo fovea in the intact peripheral retina, the so-called "preferred retinal locus" (PRL). How extensive eccentric viewing associated with central vision loss (CVL) affects brain structures responsible for visual perception and visually guided eye movements remains unknown. CVL results in a reduction of cortical gray matter in the "lesion projection zone" (LPZ) in early visual cortex, but the thickness of primary visual cortex appears to be largely preserved for eccentric-field representations. Here we explore how eccentric viewing strategies are related to cortical thickness (CT) measures in early visual cortex and in brain areas involved in the control of eye movements (frontal eye fields, FEF, supplementary eye fields, SEF, and premotor eye fields, PEF). We determined the projection zones (regions of interest, ROIs) of the PRL and of an equally peripheral area in the opposite hemifield (OppPRL) in early visual cortex (V1 and V2) in 32 patients with MD and 32 age-matched controls (19-84 years) by functional magnetic resonance imaging. Subsequently, we calculated the CT in these ROIs and compared it between PRL and OppPRL as well as between groups. Additionally, we examined the CT of FEF, SEF, and PEF and correlated it with behavioral measures like reading speed and eccentric fixation stability at the PRL. We found a significant difference between PRL and OppPRL projection zones in V1 with increased CT at the PRL, that was more pronounced in the patients, but also visible in the controls. Although the mean CT of the eye fields did not differ significantly between patients and controls, we found a trend to a positive correlation between CT in the right FEF and SEF and fixation stability in the whole patient group and between CT in the right PEF and reading speed in the JMD subgroup. The results indicate a possible association between the compensatory strategies used by patients with CVL and structural brain properties in early visual cortex and cortical eye fields.
C1 [Plank, Tina; Benkowitsch, Edith M. A.; Beer, Anton L.; Malania, Maka; Frank, Sebastian M.; Greenlee, Mark W.] Univ Regensburg, Inst Expt Psychol, Regensburg, Germany.
   [Brandl, Sabine; Jaegle, Herbert] Univ Hosp Regensburg, Dept Ophthalmol, Regensburg, Germany.
   [Frank, Sebastian M.] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA.
   [Frank, Sebastian M.] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA.
C3 University of Regensburg; University of Regensburg; Dartmouth College;
   Brown University
RP Greenlee, MW (通讯作者)，Univ Regensburg, Inst Expt Psychol, Regensburg, Germany.
EM mark.greenlee@ur.de
RI Jägle, Herbert/GPP-2945-2022
OI Beer, Anton L./0000-0002-0297-6838; Plank, Tina/0000-0001-5329-7037;
   Frank, Sebastian/0000-0002-7028-8754
FU DFG [GR988-18/1-2, PL 641/1-1]
FX Funding This study was supported by DFG GR988-18/1-2 (to MG) and PL
   641/1-1 (to TP).
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NR 76
TC 0
Z9 0
U1 0
U2 0
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD OCT 1
PY 2021
VL 15
AR 718737
DI 10.3389/fnins.2021.718737
PG 19
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA WJ5JV
UT WOS:000709081800001
PM 34658765
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hermosilla, J
   Perez-Robles, R
   Salmeron-Garcia, A
   Casares, S
   Cabeza, J
   Navas, N
AF Hermosilla, Jesus
   Perez-Robles, Raquel
   Salmeron-Garcia, Antonio
   Casares, Salvador
   Cabeza, Jose
   Navas, Natalia
TI Stability study over time of clinical solutions of ziv-aflibercept
   prepared in infusion bags using a proper combination of physicochemical
   and functional strategies
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Ziv-Aflibercept; Fc-fusion protein; Infusion bags; Stability study
ID RANIBIZUMAB
AB A range of biopharmaceutical products are used to target Vascular Endothelial Growth Factor (VEGF), including Eylea (R) (aflibercept, AFL) and Zaltrap (R) (ziv-aflibercept, ziv-AFL). The first is indicated for ophthalmological diseases such as neovascular (wet) age-related macular degeneration, while the second is used in the treatment of metastatic colorectal cancer. The stability of AFL in prefilled syringes has been widely studied; however, no research has yet been done on the stability of ziv-AFL in polyolefin infusion bags. Therefore, the purpose of the present research is to evaluate the stability of ziv-AFL (Zaltrap (R)) clinical solutions prepared under aseptic conditions in polyolefin infusion bags at two different concentrations, i.e. 4.0 and 0.6 mg/mL, and stored refrigerated in darkness at 2-8 degrees C for 14 days. With that aim, the ziv-AFL clinical solutions were assessed by analysing changes in its physicochemical and functional properties. The distribution of the particulates was studied over a range of 0.001-10 mu m by Dynamic Light Scattering (DLS); oligomers were analysed by Size-Exclusion High-Performance Chromatography with Diode Array Detection (SE/HLPC-DAD); the secondary structure of the protein was studied by far UV Circular Dichroism (CD) and the tertiary structure by Intrinsic Tryptophan Fluorescence (IT-F) and Intrinsic Protein Fluorescence (IP-F); charge variants were assessed by Strong Cation Exchange Ultra High-Performance Chromatography with UV detection (SCX/UHPLC-UV); functionality was evaluated by ELISA by measuring the biological activity as manifested in the extension of the immunological reaction of the ziv-AFL with its antigen (VEGF). Neither aggregation nor oligomerization were detected by the techniques mentioned above. Secondary and tertiary structures remained unchanged over the 14-day period, as did charge variants. The functionality observed initially was maintained along time. Therefore, it could be proposed that the ziv-AFL clinical solutions studied showed great physicochemical and functional stability over a period of two weeks, regardless of the concentration, i.e. 4 or 0.6 mg/mL. (C) 2021 The Author(s). Published by Elsevier B.V.
C1 [Hermosilla, Jesus; Perez-Robles, Raquel; Navas, Natalia] Univ Granada, Sci Fac, Inst Invest Biosanitaria Ibs Granada, Dept Analyt Chem, E-18071 Granada, Spain.
   [Salmeron-Garcia, Antonio; Cabeza, Jose] San Cecilio Univ Hosp, Inst Invest Biosanitaria Ibs Granada, Dept Clin Pharm, Granada 18016, Spain.
   [Casares, Salvador] Univ Granada, Sci Fac, Dept Phys Chem, E-18071 Granada, Spain.
C3 University of Granada; Hospital Universitario San Cecilio; University of
   Granada
RP Navas, N (通讯作者)，Fuentenueva Ave S-N, Granada 18071, Spain.
EM natalia@ugr.es
RI navas, Natalia/O-2262-2018
OI navas, Natalia/0000-0002-2536-1430
FU Project FIS (Instituto Carlos III, Ministerio de Economia y
   Competitividad, Spain) [PI-17/00547]; European Regional Development
   Funds (ERDF)
FX The study was entirely funded by Project FIS: PI-17/00547(Instituto
   Carlos III, Ministerio de Economia y Competitividad, Spain), which means
   that it was also partially supported by European Regional Development
   Funds (ERDF).
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NR 28
TC 1
Z9 2
U1 1
U2 7
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD SEP 5
PY 2021
VL 203
AR 114209
DI 10.1016/j.jpba.2021.114209
EA JUN 2021
PG 11
WC Chemistry, Analytical; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Pharmacology & Pharmacy
GA TU5IM
UT WOS:000681070000018
PM 34153938
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Droho, S
   Thomson, BR
   Makinde, HM
   Cuda, CM
   Perlman, H
   Lavine, JA
AF Droho, Steven
   Thomson, Benjamin R.
   Makinde, Hadijat M.
   Cuda, Carla M.
   Perlman, Harris
   Lavine, Jeremy A.
TI Ocular macrophage origin and heterogeneity during steady state and
   experimental choroidal neovascularization
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Age-related macular degeneration (AMD); Choroidal neovascularization
   (CNV); Angiogenesis; Macrophage
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; CR3 CD11B/CD18;
   ANGIOGENESIS; MONOCYTES; RANIBIZUMAB; INHIBITION; CELL
AB Background Neovascular age-related macular degeneration (nAMD) commonly causes vision loss from aberrant angiogenesis, termed choroidal neovascularization (CNV). Macrophages are heterogeneous cells that are necessary for experimental CNV, present in human CNV samples, and can display diverse functions, which are dependent upon both their origin and tissue microenvironment. Despite these associations, choroidal macrophage heterogeneity remains unexplored. Methods We performed multi-parameter flow cytometry on wildtype (WT) and Ccr2(-/-) mice after laser injury to identify macrophage subtypes, and determine which subsets originate from classical monocytes. To fate map tissue resident macrophages at steady state and after laser injury, we used the Cx3cr1(CreER/+) ; Rosa26(zsGFP/+) mouse model. We reanalyzed previously published single-cell RNA-seq of human choroid samples from healthy and nAMD patients to investigate human macrophage heterogeneity, disease association, and function. Results We identified 4 macrophage subsets in mice: microglia, MHCII(+)CD11c(-), MHCII(+)CD11c(+), and MHCII-. Microglia are tissue resident macrophages at steady state and unaffected by laser injury. At steady state, MHCII- macrophages are long lived, tissue resident macrophages, while MHCII(+)CD11c(-) and MHCII(+)CD11c(+) macrophages are partially replenished from blood monocytes. After laser injury, MHCII(+)CD11c(-) macrophages are entirely derived from classical monocytes, MHCII- macrophages originate from classical monocytes (90%) and an expansion of tissue resident macrophages (10%), and MHCII(+)CD11c(+) macrophages are derived from classical monocytes (70%), non-classical monocytes (10%), and an expansion of tissue resident macrophages (20%). Single-cell RNA-seq analysis of human choroid found 5 macrophage subsets: two MHCII(+)CD11C(-) and three MHCII(+)CD11C(+) populations. One MHCII(+)CD11C(+) subset was 78% derived from a patient with nAMD. Differential expression analysis identified up-regulation of pro-angiogenic gene expression in one MHCII(+)CD11C(-) and two MHCII(+)CD11C(+) subsets, including the disease-associated cluster. The upregulated MHCII(+)CD11C(-) pro-angiogenic genes were unique compared to the increased MHCII(+)CD11C(+) angiogenesis genes. Conclusions Macrophage origin impacts heterogeneity at steady state and after laser injury in mice. Both mice and human patients demonstrate similar macrophage subtypes. Two discrete pro-angiogenic macrophage populations exist in the human choroid. Targeting specific, pro-angiogenic macrophage subsets is a potential novel therapeutic for nAMD.
C1 [Droho, Steven; Lavine, Jeremy A.] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, 240 E Huron St,McGaw M343, Chicago, IL 60611 USA.
   [Thomson, Benjamin R.] Northwestern Univ, Feinberg Sch Med, Feinberg Cardiovasc & Renal Res Inst, Div Nephrol & Hypertens,Dept Med, Chicago, IL 60611 USA.
   [Makinde, Hadijat M.; Cuda, Carla M.; Perlman, Harris] Northwestern Univ, Dept Med, Div Rheumatol, Feinberg Sch Med, Chicago, IL 60611 USA.
C3 Northwestern University; Feinberg School of Medicine; Northwestern
   University; Feinberg School of Medicine; Northwestern University;
   Feinberg School of Medicine
RP Lavine, JA (通讯作者)，Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, 240 E Huron St,McGaw M343, Chicago, IL 60611 USA.
EM jeremy.lavine@northwestern.edu
OI Lavine, Jeremy/0000-0002-0884-1336; Makinde,
   Hadijat-Kubura/0000-0001-8492-4187
FU NIH [K08 EY030923, R01 EY025799, R01 HL 134375, AR064546, HL134375,
   AG049665, UH2AR067687]; Lupus Research Alliance Novel Research Grant;
   Northwestern University Dixon Translational Research Grant Initiative
   Award; United States-Israel Binational Science Foundation [2013247];
   Rheumatology Research Foundation (Agmt); Rheumatology Precision Medicine
   Fund
FX BRT was supported by NIH grant R01 EY025799. HM is supported by NIH
   grant R01 HL 134375 (Diversity Supplement). CMC was supported by a Lupus
   Research Alliance Novel Research Grant and a Northwestern University
   Dixon Translational Research Grant Initiative Award. HP was supported by
   NIH grant AR064546, HL134375, AG049665, UH2AR067687, the United
   States-Israel Binational Science Foundation (2013247), and the
   Rheumatology Research Foundation (Agmt 05/06/14). HP was also supported
   by the Mabel Greene Myers Professor of Medicine and generous donations
   to the Rheumatology Precision Medicine Fund. JAL was supported by NIH
   grant K08 EY030923. No funding body had any role in the design of the
   study, collection, analysis, interpretation of data, or in writing the
   manuscript.
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NR 49
TC 6
Z9 6
U1 1
U2 6
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD NOV 13
PY 2020
VL 17
IS 1
AR 341
DI 10.1186/s12974-020-02010-0
PG 19
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA OR4JY
UT WOS:000589439900001
PM 33187533
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kumar, B
   Gupta, SK
   Saxena, R
   Srivastava, S
AF Kumar, B.
   Gupta, S. K.
   Saxena, R.
   Srivastava, S.
TI Current trends in the pharmacotherapy of diabetic retinopathy
SO JOURNAL OF POSTGRADUATE MEDICINE
LA English
DT Review
DE Anti-angiogenic agents; corticosteroids; diabetic retinopathy
ID RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIAL; INTRAVITREAL
   TRIAMCINOLONE ACETONIDE; OVINE HYALURONIDASE VITRASE(R);
   PLACEBO-CONTROLLED TRIAL; DRUG-DELIVERY SYSTEM; MACULAR EDEMA;
   BEVACIZUMAB AVASTIN; PPAR-ALPHA; PANRETINAL PHOTOCOAGULATION
AB Diabetic retinopathy (DR) is one of the most debilitating disorders of microvasculature of the retina and one of the leading causes of vision loss among the working class worldwide. At present, intravitreal anti-inflammatory (corticosteroids) and anti-angiogenesis (anti-Vascular Endothelial Growth Factor) agents are being used as wide options for the pharmacotherapy of DR and diabetic macular edema (DME). Anti-inflammatory agents (Triamcinolone acetonide and other agents) have shown evidence-based clinical benefits in various randomized clinical trials for the treatment of DR and DME, and also shown improvement in best corrected visual acuity. However, direct intravitreal injections are associated with serious side-effects like cataract and elevation of Intra Ocular Pressure. Despite this, corticosteroid therapy has been effective for DR and DME, therefore current focus is on the development of novel intravitreal steroid delivery devices that release a small quantity over a prolonged period of time. In addition to corticosteroids, anti-angiogenic agents are found to be effective for the treatment of DR and DME. The most popular target of these agents is the subfamily of proteins known as VEGF, whose over-expression is believed to play a role in numerous diseases including DR and Age-related Macular Degeneration. Intravitreal bevacizumab (Avastin(R)) and Ranibizumab (Lucentis(R)) are gaining popularity as a clinical adjunct to panretinal photocoagulation in patients with proliferative DR. Moreover, Lucentis has been recently approved by the United States Food and Drug Administration for macular edema following retinal vein occlusion. Further, systemic agents (specially, hypoglycemic, hypolipidemic and anti-hypertensive agents) have shown beneficial results in reducing the progression of DR. In conclusion, it can be stated that for the present scenario systematic use of available pharmacotherapy as an adjunct to laser photocoagulation, which is gold standard therapy, can be a useful tool in the prevention of vision loss from DR and related disorders. This article summarizes the up-to-date developments in the pharmacotherapy of DR. Method- Literature search was done on online database, Pubmed, Google Scholar, clinitrials.gov and browsing through individual ophthalmology journals and leading pharmaceutical company websites.
C1 [Kumar, B.; Gupta, S. K.; Srivastava, S.] Univ Delhi, Dept Pharmacol, Ocular Lab, Delhi Inst Pharmaceut Sci & Res, New Delhi, India.
   [Saxena, R.] All India Inst Med Sci, Dr RP Ctr Ophthalm Sci, New Delhi, India.
C3 Meenakshi Academy of Higher Education & Research (MAHER); Delhi
   Pharmaceutical Sciences & Research University (DPSRU); Delhi Institute
   of Pharmaceutical Sciences & Research; University of Delhi; All India
   Institute of Medical Sciences (AIIMS) New Delhi; Dr. Rajendra Prasad
   Centre for Ophthalmic Sciences
RP Gupta, SK (通讯作者)，Univ Delhi, Dept Pharmacol, Ocular Lab, Delhi Inst Pharmaceut Sci & Res, New Delhi, India.
EM skgup@hotmail.com
OI Srivastava, Sushma/0000-0002-1172-4982; Gupta,
   Sanjeev/0000-0002-2014-5333; Balasubramanian, Kumar/0000-0002-1199-4587
FU Department of Science & Technology under DPRP
FX Financial support from the Department of Science & Technology under DPRP
   is gratefully acknowledged.
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NR 74
TC 47
Z9 48
U1 0
U2 35
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
   INDIA
SN 0022-3859
J9 J POSTGRAD MED
JI J. Postgrad. Med.
PD APR-JUN
PY 2012
VL 58
IS 2
BP 132
EP 139
DI 10.4103/0022-3859.97176
PG 8
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 971DG
UT WOS:000306183300008
PM 22718058
OA gold
DA 2022-11-30
ER

PT J
AU Rosenfeld, PJ
   Shapiro, H
   Tuomi, L
   Webster, M
   Elledge, J
   Blodi, B
AF Rosenfeld, Philip J.
   Shapiro, Howard
   Tuomi, Lisa
   Webster, Mary
   Elledge, Julee
   Blodi, Barbara
CA MARINA Study Grp
   ANCHOR Study Grp
TI Characteristics of Patients Losing Vision after 2 Years of Monthly
   Dosing in the Phase III Ranibizumab Clinical Trials
SO OPHTHALMOLOGY
LA English
DT Article
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; REPORT NO. 3; MACULAR
   DEGENERATION; PHOTODYNAMIC THERAPY; VERTEPORFIN THERAPY; SUBGROUP
   ANALYSIS; VISUAL-ACUITY; TAP; PEGAPTANIB; ANCHOR
AB Purpose: To investigate the cause of visual acuity (VA) loss in patients with neovascular age-related macular degeneration (AMD) receiving monthly ranibizumab injections in the pivotal ranibizumab phase III trials.
   Design: Retrospective analysis.
   Participants: The Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab In the treatment of Neovascular AMD (MARINA) and Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trials.
   Methods: Demographics and lesion characteristics at baseline and month 24 were compared in patients with >= 15 letters VA loss and patients with >= 15 letters VA gain from baseline to month 24. Additional evaluations of fundus photographs from these patients were performed to assess features of non-exudative AMD, such as geographic atrophy (GA) and retinal pigment epithelium (RPE) abnormalities.
   Main Outcome Measures: Differences in lesion characteristics between patients who lost versus gained >= 15 letters of VA from baseline to month 24.
   Results: At month 24, 9% of ranibizumab-treated patients from MARINA and 10% of ranibizumab-treated patients from ANCHOR had lost >= 15 letters VA; 30% of ranibizumab-treated patients from MARINA and 38% of ranibizumab-treated patients from ANCHOR had gained >= 15 letters VA. Baseline characteristics associated with VA loss at month 24 included older age, better VA, and larger lesions. At month 24, an increased area of RPE abnormality was associated with VA loss in both the MARINA (P = 0.0008) and ANCHOR (P = 0.0046) trials. Increased total lesion area at month 24 was associated with VA loss in both trials. In MARINA, the increase in total lesion area was attributable to an increase in the angiographic designation of atrophic scar among VA losers (P = 0.0043), but in ANCHOR it was attributable to an increased area of choroidal neovascularization (CNV) (P = 0.039) but not an increased area of leakage (P = 0.17). Increased areas of GA, fibrosis, and hemorrhage were not associated with VA loss.
   Conclusions: Vision loss after 2 years of monthly ranibizumab therapy was associated with lesion characteristics commonly associated with suppressed CNV, such as pigmentary abnormalities, atrophic scar, and the absence of leakage. Future VA improvements in patients receiving ranibizumab therapy may require preservation of photoreceptor and RPE function rather than strategies that target CNV.
C1 [Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Shapiro, Howard; Tuomi, Lisa] Genentech Inc, San Francisco, CA 94080 USA.
   [Webster, Mary; Elledge, Julee; Blodi, Barbara] Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI USA.
C3 Bascom Palmer Eye Institute; University of Miami; Roche Holding;
   Genentech; University of Wisconsin System; University of Wisconsin
   Madison
RP Rosenfeld, PJ (通讯作者)，Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
EM prosenfeld@med.miami.edu
FU Genentech, Inc.; Genentech
FX Genentech, Inc.; Proprietary interest statement: PJR has received
   additional clinical research grants from Genentech and payment for
   participating on Genentech's advisory boards and speaker's bureau
   program; received clinical research grants from competing companies;
   participated in competing scientific advisory boards; and received
   reimbursement for travel expenses. HS and LT are employees of Genentech.
   The Fundus Photograph Reading Center at the University of Wisconsin
   receives research funding from Genentech and competing companies.
CR [Anonymous], STUDY RANIBIZUMAB AD
   [Anonymous], COMPARISON AGE RELAT
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NR 21
TC 194
Z9 209
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAR
PY 2011
VL 118
IS 3
BP 523
EP 530
DI 10.1016/j.ophtha.2010.07.011
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 729QA
UT WOS:000287964400016
PM 20920825
DA 2022-11-30
ER

PT J
AU Smretschnig, E
   Krebs, I
   Moussa, S
   Ansari-Shahrezarei, S
   Binder, S
AF Smretschnig, Eva
   Krebs, Ilse
   Moussa, Sarah
   Ansari-Shahrezarei, Siamak
   Binder, Susanne
TI Cirrus OCT versus Spectralis OCT: differences in segmentation in
   fibrovascular pigment epithelial detachment
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration (AMD); Fibrovascular pigment epithelial
   detachment (PED); Retinal thickness (RT); Spectral domain optical
   coherence tomography (SD-OCT); Threshold algorithm
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR THICKNESS MEASUREMENTS;
   TIME-DOMAIN
AB Background Automatically measurements of retinal thickness by optical coherence tomography (OCT) facilitate the assessment of various retinal diseases. The aim of this retrospective study was to report macular thickness measurements in eyes with vascular pigment epithelial detachment (PED) due to age-related macular degeneration (AMD) by using two different commercially available spectral domain (SD) OCT instruments and to consequently point out differences in their algorithm software.systems.
   Methods OCT images of patients with vascular PED due to AMD, obtained with Cirrus and Spectralis OCT, were retrospectively analyzed. Main objectives were to observe differences in central retinal thickness (CRT) values and failures in automated threshold delineation, as well as central point thickness values obtained after manual correction of threshold lines. Scanning with the Cirrus HD OCT was performed with the 512 x 128 scan pattern; scans performed with the Spectralis OCT were 20 x 15 degree raster scans consisting of 19 high-speed line scans.
   Results OCT images of 34 eyes of 28 patients with a mean age of 71 years and a mean distance visual acuity (VA) of 0.70 ETDRS were analyzed. Mean central retinal thickness (CRT) was 262.38 mu m +/- 133.18 (176-507 mu m) in Cirrus and 337.82 mu m +/- 137.75 (277-790 mu m) in Spectralis scans, mainly caused by different software approaches in positioning the posterior threshold line, following the PED in Cirrus OCT whereas remaining unelevated in Spectralis OCT. There were failures in positioning the outer retinal boundary line in 50% of Cirrus scans and in 73.52% of Spectralis scans. We obtained the mean value of central point neurosensory retinal thickness of each central single scan after manual delineation, and found a significant correlation (r=0.819, p<0.001).
   Conclusions Our study indicates that there are significant differences in CRT values in patients with vascular PED, due to different segmentation algorithms and a high error rate in automatically set threshold lines. When planning and conducting multicenter studies, one has to be especially aware of the differences in delineating threshold algorithm lines by different SD OCT devices.
C1 [Smretschnig, Eva; Krebs, Ilse; Moussa, Sarah; Ansari-Shahrezarei, Siamak; Binder, Susanne] Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, A-1030 Vienna, Austria.
   [Smretschnig, Eva; Krebs, Ilse; Ansari-Shahrezarei, Siamak; Binder, Susanne] Rudolf Fdn Clin, Dept Ophthalmol, Vienna, Austria.
   [Ansari-Shahrezarei, Siamak] Med Univ Graz, Dept Ophthalmol, Graz, Austria.
C3 Ludwig Boltzmann Institute; Medical University of Graz
RP Smretschnig, E (通讯作者)，Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, Juchgasse 25, A-1030 Vienna, Austria.
EM eva.smretschnig@gmx.at
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NR 16
TC 20
Z9 21
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD DEC
PY 2010
VL 248
IS 12
BP 1693
EP 1698
DI 10.1007/s00417-010-1415-9
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 687WW
UT WOS:000284810000002
PM 20496152
DA 2022-11-30
ER

PT J
AU Loane, E
   McKay, GJ
   Nolan, JM
   Beatty, S
AF Loane, Edward
   McKay, Gareth J.
   Nolan, John M.
   Beatty, Stephen
TI Apolipoprotein E Genotype Is Associated with Macular Pigment Optical
   Density
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; FOOD-FREQUENCY QUESTIONNAIRE; E GENE; E
   POLYMORPHISMS; RISK-FACTORS; EPSILON-4 ALLELE; PRIMATE RETINAS; BINDING
   PROTEIN; IN-VITRO; DEGENERATION
AB PURPOSE. Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk factors for this condition may be classified as genetic and environmental. Apolipoprotein E is putatively involved in the transport of the macular pigment (MP) carotenoids lutein (L) and zeaxanthin (Z) in serum and may also influence retinal capture of these compounds. This study was designed to investigate the relationship between macular pigment optical density (MPOD) and ApoE genotype.
   METHODS. This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. Serum L and Z were measured by HPLC. ApoE genotyping was performed by direct polymerase chain reaction amplification and DNA nucleotide sequencing from peripheral blood.
   RESULTS. Genotype data were available on 300 of the 302 (99.3%) subjects. The mean (+/- SD) age of the subjects in this study was 47.89 +/- 11.05 (range, 21-66) years. Subjects were classed into one of three ApoE genotype groups, as follows: group 1, epsilon 2 epsilon 2 or epsilon 2 epsilon 3; group 2, epsilon 3 epsilon 3; group 3, epsilon 2 epsilon 4 or epsilon 3 epsilon 4 or epsilon 4 epsilon 4. All three groups were statistically comparable in terms of age, sex, body mass index, cigarette smoking, and dietary and serum levels of L and Z. There was a statistically significant association between ApoE genotype and MPOD. Subjects who had at least one epsilon 4 allele had a higher MPOD across the macula than subjects without this allele (group 1 MPOD area, 0.70 +/- 0.40; group 2 MPOD area, 0.67 +/- 0.42; group 3 MPOD area, 0.85 +/- 0.46; one-way ANOVA, P = 0.014.
   CONCLUSIONS. These results suggest that ApoE genotype status is associated with MPOD. This association may explain, at least in part, the putative protective effect of the epsilon 4 allele for AMD and is consistent with the view that apolipoprotein profile influences the transport and/or retinal capture of circulating L and/or Z. (Invest Ophthalmol Vis Sci. 2010;51:2636-2643) DOI:10.1167/iovs.09-4397
C1 [Loane, Edward; Nolan, John M.; Beatty, Stephen] Waterford Inst Technol, Dept Chem & Life Sci, Macular Pigment Res Grp, Waterford, Ireland.
   [Loane, Edward] Royal Victorian Eye & Ear Hosp, Dept Ophthalmol, Dublin, Ireland.
   [McKay, Gareth J.] Queens Univ Belfast, Ctr Vis & Vasc Sci, Belfast, Antrim, North Ireland.
   [Beatty, Stephen] Whitfield Clin, Waterford, Ireland.
C3 South East Technological University (SETU); Queens University Belfast
RP Loane, E (通讯作者)，Waterford Inst Technol, Dept Chem & Life Sci, Macular Pigment Res Grp, Waterford, Ireland.
EM edwardloane@yahoo.com
RI McKay, Gareth/AAZ-2601-2020; Nolan, John/N-4921-2014
OI McKay, Gareth/0000-0001-8197-6280; Nolan, John/0000-0002-5503-7084
FU European Union; Bausch Lomb Ireland
FX Supported by a European Union Strand 1 research grant and by a Bausch &
   Lomb Ireland research grant.
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   [No title captured]
NR 83
TC 36
Z9 36
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2010
VL 51
IS 5
BP 2636
EP 2643
DI 10.1167/iovs.09-4397
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 589UU
UT WOS:000277180500046
PM 20107178
OA Green Accepted, Green Submitted
DA 2022-11-30
ER

PT J
AU Grieve, R
   Guerriero, C
   Walker, J
   Tomlin, K
   Langham, J
   Harding, S
   Chakravathy, U
   Carpenter, J
   Reeves, BC
AF Grieve, Richard
   Guerriero, Carla
   Walker, Jemma
   Tomlin, Keith
   Langham, Julia
   Harding, Simon
   Chakravathy, Usha
   Carpenter, James
   Reeves, Barnaby C.
CA Verteporfin Photodynamic Therapy
TI Verteporfin Photodynamic Therapy Cohort Study Report 3: Cost
   Effectiveness and Lessons for Future Evaluations
SO OPHTHALMOLOGY
LA English
DT Article
ID LOW-VISION AIDS; MACULAR DEGENERATION; VISUAL IMPAIRMENT; UTILITY;
   IMPACT; MODEL; EYES
AB Purpose: To report (1) the costs of verteporfin photodynamic therapy (VPDT) in routine treatment of neovascular age-related macular degeneration (nAMD), (2) the relationship between health and social service costs and best-corrected visual acuity (BCVA), (3) the cost-effectiveness of VPDT versus a best supportive care (BSC) group who were assumed to have no active treatment, and (4) lessons for future cost-effectiveness analyses (CEAs).
   Design: The CEA of VPDT versus BSC that uses health-related quality of life (HrQoL), resource use, and visual acuity data from the United Kingdom (UK) VPDT Cohort Study.
   Participants: Data on VPDT use were collected from patients attending 45 ophthalmology provider units in the UK National Health Service, 15 units collected data on self-reported use of services.
   Methods: Incremental costs of VFDT versus BSC were calculated from treatment costs, change in cost associated with declining BCVA, and difference in BCVA previously attributed to VPDT. Similarly, incremental quality-adjusted life years (QALYs) were calculated from change in HRQoL associated with declining BCVA, giving an incremental cost per QALY of VPDT versus BSC over 2 years.
   Main Outcome Measures: Incremental costs (UK pounds []; pound United States dollars [$]); incremental QALYs; costs per QALY.
   Results: The treatment costs of VDPT were 3026 pound ($4544) in year 1 and 845 pound ($1269) in year 2. For patients who used services, a 5-letter decrease in BCVA was associated with an increase in annual costs of approximately 110 pound ($165; 95% confidence intervals, approximately 48 pound [$72] to 174 pound [$261]). The incremental costs and QALYs for VPDT were 3514 pound ($5276) and 0.021, respectively, giving incremental costs per QALY gained of 170 pound 000 ($255 000).
   Conclusions: Verteporfin photodynamic therapy is unlikely to be cost effective for patients with nAMD. This article provides realistic estimates of VPDT costs and the costs associated with declining vision. Future studies can follow this approach to assess accurately the cost effectiveness of new interventions for nAMD.
   Financial Disclosure(s). Proprietary or commercial disclosure may be found after the references. Ophthalmology 2009;116:2471-2477 (C) 2009 by the American Academy of Ophthalmology.
C1 [Grieve, Richard; Guerriero, Carla; Walker, Jemma; Tomlin, Keith; Langham, Julia; Carpenter, James; Reeves, Barnaby C.] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England.
   [Harding, Simon] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England.
   [Chakravathy, Usha] Queens Univ Belfast, Belfast, Antrim, North Ireland.
C3 University of London; London School of Hygiene & Tropical Medicine;
   Royal Liverpool & Broadgreen University Hospitals NHS Trust; Royal
   Liverpool University Hospital; University of Liverpool; Queens
   University Belfast
RP Grieve, R (通讯作者)，Univ London London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England.
EM richard.grieve@lshtm.ac.uk
RI Chong, Victor/Q-6565-2018
OI Chong, Victor/0000-0002-7693-522X; Harding, Simon/0000-0003-4676-1158;
   Carpenter, James/0000-0003-3890-6206; Grieve,
   Richard/0000-0001-8899-1301
FU UK National Institute for Health Research, Health Technology Assessment
   Programme [03/36/01]
FX Supported by The UK National Institute for Health Research, Health
   Technology Assessment Programme (project no.: 03/36/01), Southampton,
   England.
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NR 35
TC 9
Z9 9
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD DEC
PY 2009
VL 116
IS 12
BP 2471
EP 2477
DI 10.1016/j.ophtha.2009.10.023
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 530HE
UT WOS:000272579200031
PM 19948278
DA 2022-11-30
ER

PT J
AU Kim, RY
   Ma, GJ
   Park, WK
   Kim, M
   Park, YG
   Park, YH
AF Kim, Rae-Young
   Ma, Gun-Jung
   Park, Woo-Kyung
   Kim, Mirinae
   Park, Young-Gun
   Park, Young-Hoon
TI Clinical course after the onset of choroidal neovascularization in eyes
   with central serous chorioretinopathy
SO MEDICINE
LA English
DT Article
DE central serous chorioretinopathy; choroidal neovascularization;
   prognosis; visual acuity
ID TERM FOLLOW-UP; COHERENCE TOMOGRAPHY ANGIOGRAPHY; PIGMENT EPITHELIAL
   DETACHMENTS; ARGON-LASER PHOTOCOAGULATION; DEGENERATION
AB Chronic central serous chorioretinopathy (CSC) can be complicated with choroidal neovascularization (CNV); however, the timing of its occurrence and its clinical significance are not well understood. This study aimed to observe the time of choroidal neovascularization detection after CSC diagnosis and determine whether clinical features and prognosis differed in patients with chronic CSC or age-related retinal degeneration. In this retrospective study, medical records of CSC patients complicated with CNV who visited Seoul St. Mary's hospital of Korea between October 2009 and December 2020 were reviewed. The presence of CNV was determined using fluorescein, indocyanine green, or optical coherent tomography angiography (OCTA). Based on the patients' medical records, we observed the change of clinical pattern, best-corrected visual acuity (BCVA) and central macular thickness (CMT) at CNV detection and at 6 months, 1 year, 3 years, and 5 years following CNV detection. Thirty eyes of 30 patients (male: female ratio of 13:17) were enrolled. Mean age at diagnosis of CSC was 54.0 +/- 8.5 years (mean +/- standard deviation). On average, CNV was detected 1.65 +/- 2.30 years after the diagnosis of CSC. The mean CMT was significantly decreased at 6 months, 1 year, and 3 years after choroidal neovascularization detection (P < .001, P < .001, P = .001 respectively). BCVA tend to improve after CNV detection, but there was no statistical significance at 6 months, 1 year, 3 years, and 5 years (all with P > .05). There were no clinical findings suggesting age-related macular degeneration such as intraretinal, subretinal hemorrhage or drusen in any of the case during follow-up. None of the subjects had severe visual acuity loss of 1.0 logarithm of the minimum angle of resolution (logMAR) (20/200 Snellen equivalent) or greater. Among the subjects, 6 patients (20%) did not require any treatment during observation, while 24 other patients required anti-vascular endothelial growth factor (anti-VEGF) or photodynamic therapy. At the last visit, 22 patients (73.3%) remained stable for more than 6 months, without subretinal fluid recurrence. Choroidal neovascularization was detected earlier than previously reported. There was no rapid deterioration of visual acuity or clinical features even after CNV detection.
C1 [Kim, Rae-Young; Ma, Gun-Jung; Park, Woo-Kyung; Kim, Mirinae; Park, Young-Gun; Park, Young-Hoon] Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Ophthalmol & Visual Sci, Seoul, South Korea.
   [Kim, Rae-Young; Park, Woo-Kyung; Kim, Mirinae; Park, Young-Gun; Park, Young-Hoon] Catholic Univ Korea, Coll Med, Catholic Inst Visual Sci, Seoul, South Korea.
C3 Catholic University of Korea; Seoul St. Mary's Hospital; Catholic
   University of Korea
RP Park, YH (通讯作者)，Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Ophthalmol & Visual Sci, Seoul, South Korea.; Park, YH (通讯作者)，Catholic Univ Korea, Coll Med, Catholic Inst Visual Sci, Seoul, South Korea.
EM parkyh@catholic.ac.kr
FU Basic Science Research Program through the National Research Foundation
   of Korea [NRF-2020R1F1A1074898]
FX This study was supported by the Basic Science Research Program through
   the National Research Foundation of Korea (NRF-2020R1F1A1074898).
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NR 32
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7974
EI 1536-5964
J9 MEDICINE
JI Medicine (Baltimore)
PD AUG 27
PY 2021
VL 100
IS 34
AR e26980
DI 10.1097/MD.0000000000026980
PG 8
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA UJ6CG
UT WOS:000691370700033
PM 34449466
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Urbano, CA
   Maatouk, C
   Greenlee, T
   Chen, A
   Conti, TF
   Briskin, I
   Singh, RP
AF Urbano, Catherine A.
   Maatouk, Christopher
   Greenlee, Tyler
   Chen, Andrew
   Conti, Thais F.
   Briskin, Isaac
   Singh, Rishi P.
TI Real-World Treatment Patterns in a Population With Neovascular AMD
   Treated With Anti-VEGF Agents
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID VISUAL-ACUITY OUTCOMES; MACULAR DEGENERATION; RANIBIZUMAB; EXTEND;
   BEVACIZUMAB; AFLIBERCEPT
AB BACKGROUND AND OBJECTIVES: To characterize mean number of injections, injection type, and injection frequency during the first year of treatment; assess factors significantly related to injection interval; and identify predictive factors related to patient outcomes.
   PATIENTS AND METHODS: A retrospective, non-comparative, nonrandomized cohort study of ocular treatment with intravitreal injections of bevacizumab, ranibizumab, and aflibercept in eyes with neovascular age-related macular degeneration (nAMD). Data from January 1, 2012, through March 31, 2018, were systematically extracted from the electronic medical record system at Cole Eye Institute. Eligible patients had three or more injections within the first 12 months of treatment and received no prior injections.
   RESULTS: Patients received an average 8.12 +/- 2.45 injections, and 45% of patients received injections at an interval of 8 weeks or less (<= q8 weeks), 33% received injections at 8 to 12 weeks (q8-12 weeks), and 22% received injections at greater than 12 weeks (>q12 weeks). Age (P =.007) and initial central subfield thickness (CST) (P =.043) had statistically significant trend relationships (P =.007) with injection interval, whereas younger patients and patients with higher CST measurements tended to have shorter injection intervals. Injection interval was a significant predictor of visual acuity (VA) and CST. Patients receiving injections at q8-12 weeks were more likely to have better VA outcomes than patients with injection intervals at =q8 weeks (odds ratio [OR] = 1.66 [1.16, 2.37]; P =.005). Patients receiving injections at >q12 weeks did not show a significant improvement in VA (P =.06) and were more likely to have worse CST outcomes than patients receiving injections at =q8 weeks (OR = 1.95 [1.17, 3.26]; P =.011).
   CONCLUSION: A significant portion of patients receive injections at an interval longer than every 8 weeks. Age and baseline CST had a significant relationship with injection interval. Injection interval was a significant predictor of VA and CST at 1 year. Patients with an injection interval of >q12 weeks tended to have less VA improvement and CST reduction compared to the =q8 weeks and q8-12 weeks groups. These findings suggest an extended injection interval >q12 weeks may be at the expense of potential VA improvement.
C1 [Urbano, Catherine A.; Maatouk, Christopher; Greenlee, Tyler; Chen, Andrew; Conti, Thais F.; Singh, Rishi P.] Cleveland Clin, Ctr Ophthalm Bioinformat, Cole Eye Inst, Cleveland, OH 44195 USA.
   [Urbano, Catherine A.; Maatouk, Christopher; Chen, Andrew; Singh, Rishi P.] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA.
   [Greenlee, Tyler] Ohio Univ, Heritage Coll Osteopath Med, Cleveland Campus, Warrensville Hts, OH USA.
   [Briskin, Isaac] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA.
C3 Cleveland Clinic Foundation; Case Western Reserve University; University
   System of Ohio; Ohio University; Cleveland Clinic Foundation
RP Singh, RP (通讯作者)，Cleveland Clin, Cole Eye Inst, 9500 Euclid Ave,I-32, Cleveland, OH 44195 USA.
EM singhr@ccf.org
CR Abedi F, 2014, RETINA-J RET VIT DIS, V34, P1531, DOI 10.1097/IAE.0000000000000134
   [Anonymous], GLOBAL TRENDS RETINA
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NR 28
TC 2
Z9 2
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD APR
PY 2021
VL 52
IS 4
BP 190
EP 198
DI 10.3928/23258160-20210330-03
PG 9
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA RP5CB
UT WOS:000641744800003
PM 34039184
DA 2022-11-30
ER

PT J
AU Treumer, F
   Wienand, S
   Purtskhvanidze, K
   Roider, J
   Hillenkamp, J
AF Treumer, F.
   Wienand, S.
   Purtskhvanidze, K.
   Roider, J.
   Hillenkamp, J.
TI The role of pigment epithelial detachment in AMD with submacular
   hemorrhage treated with vitrectomy and subretinal co-application of rtPA
   and anti-VEGF
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Submacular hemorrhage; Age-related macular degeneration; Pigment
   epithelial detachment; rtPA; Bevacizumab
ID MACULAR DEGENERATION; VISUAL-ACUITY; RPE TEARS; RANIBIZUMAB; INJECTION;
   THERAPY; RISK
AB To assess the incidence of pigment epithelial detachment (PED) in age-related macular degeneration (AMD) with submacular hemorrhage (SMH) and its response to treatment with pars plana vitrectomy (ppV), subretinal co-application of recombinant tissue plasminogen activator (rtPA) and anti-VEGF, and an intravitreal gas tamponade.
   Consecutive interventional case series of 132 eyes of 129 patients with neovascular AMD with SMH. All eyes underwent ppV with subretinal co-application of rtPA and bevacizumab followed by a gas tamponade. Postoperatively, two additional intravitreal anti-VEGF injections were applied monthly, followed by intravitreal anti-VEGF injections applied PRN thereafter. PEDs and SMHs were evaluated with SD-OCT pre- and postoperatively.
   Preoperatively, 88 of 132 (67%) eyes were examined by OCT, and in 81 of these eyes the RPE could be visualised. A PED was found in 74 (91%) eyes, and no PED was found in five (6%) eyes. Median height of preoperative PED was 503 mu m (range 150-1242, n = 65) and reduced to 344 (n = 62) and 306 mu m (n = 27) after 3 and 12 months respectively. Two eyes showed a pre-existing rip of the RPE. Postoperatively, a rip was documented in 12 of 128 (9%) eyes. Median height of SMH was 762 mu m (range 217-1840), median diameter was 4.3 (1.5-15) disc diameter. A complete displacement of the SMH from the fovea was achieved in 112 of 129 (87%) eyes. Overall, median best-corrected logMAR visual acuity (BCVA) improved significantly from preoperative 1.6 (0.5-2.0, n = 132) to 1.0 (0.2-2.0) 3 (n = 132) and 12 months (n = 74) postoperatively. Excluding eyes with pre-existing macular scars (n = 22), BCVA 3 months postoperatively was 0.8. Height of PED or SMH did not correlate with postoperatively BCVA, while size of SMH showed a mild correlation (rho = 0.25, p = 0.005).
   PpV with subretinal co-application of rtPA and bevacizumab and an intravitreal gas tamponade effectively displaces SMH and improves BCVA. Preoperatively, PED is found in the majority of eyes. Height of PED or SMH did not correlate with postoperatively BCVA. Tears of the RPE occur as frequently as in exudative AMD without SMH.
C1 [Treumer, F.; Wienand, S.; Purtskhvanidze, K.; Roider, J.; Hillenkamp, J.] Univ Med Ctr Schleswig Holstein, Dept Ophthalmol, Campus Kiel,Arnold Heller Str 3, D-24105 Kiel, Germany.
   [Hillenkamp, J.] Univ Med Ctr Wurzburg, Dept Ophthalmol, Josef Schneider Str 11, D-97080 Wurzburg, Germany.
C3 University of Kiel; Schleswig Holstein University Hospital; University
   of Wurzburg
RP Treumer, F (通讯作者)，Univ Med Ctr Schleswig Holstein, Dept Ophthalmol, Campus Kiel,Arnold Heller Str 3, D-24105 Kiel, Germany.
EM felix.treumer@uksh.de
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NR 27
TC 15
Z9 17
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUN
PY 2017
VL 255
IS 6
BP 1115
EP 1123
DI 10.1007/s00417-017-3620-2
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EV0NL
UT WOS:000401437600009
PM 28280989
DA 2022-11-30
ER

PT J
AU Uji, A
   Abdelfattah, NS
   Boyer, DS
   Balasubramanian, S
   Lei, JQ
   Sadda, SR
AF Uji, Akihito
   Abdelfattah, Nizar Saleh
   Boyer, David S.
   Balasubramanian, Siva
   Lei, Jianqin
   Sadda, SriniVas R.
TI Variability of Retinal Thickness Measurements in Tilted or Stretched
   Optical Coherence Tomography Images
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE optical coherence tomography; retinal thickness; retina
ID MACULAR DEGENERATION; PATHOLOGICAL MYOPIA; DOMAIN; EYES; OCT;
   REPRODUCIBILITY; SEGMENTATION; VOLUME; EDEMA; LASER
AB Purpose: To investigate the level of inaccuracy of retinal thickness measurements in tilted and axially stretched optical coherence tomography (OCT) images.
   Methods: A consecutive series of 50 eyes of 50 patients with age-related macular degeneration were included in this study, and Cirrus HD-OCT images through the foveal center were used for the analysis. The foveal thickness was measured in three ways: (1) parallel to the orientation of the A-scan (Tx), (2) perpendicular to the retinal pigment epithelium (RPE) surface in the instrument-displayed aspect ratio image (Ty), and (3) thickness measured perpendicular to the RPE surface in a native aspect ratio image (Tz). Mathematical modeling was performed to estimate the measurement error.
   Results: The measurement error was larger in tilted images with a greater angle of tilt. In the simulation, with axial stretching by a factor of 2, Ty/Tz ratio was > 1.05 at a tilt angle between 13 degrees to 18 degrees and 72 degrees to 77 degrees, > 1.10 at a tilt angle between 19 degrees to 31 degrees and 59 degrees to 71 degrees, and > 1.20 at an angle ranging from 32 degrees to 58 degrees. Of note with even more axial stretching, the Ty/Tz ratio is even larger. Tx/Tz ratio was smaller than the Ty/Tz ratio at angles ranging from 0 degrees to 54 degrees. The actual patient data showed good agreement with the simulation.
   The Ty/Tz ratio was greater than 1.05 (5% error) at angles ranging from 13 degrees to 18 degrees and 72 degrees to 77 degrees, > greater than 1.10 (10% error) angles ranging from 19 degrees to 31 degrees and 59 degrees to 71 degrees, and greater than > 1.20 (20% error) angles ranging from 32 degrees to 58 degrees in the images axially stretched by a factor of 2 (b/a = 2), which is typical of most OCT instrument displays.
   Conclusions: Retinal thickness measurements obtained perpendicular to the RPE surface were overestimated when using tilted and axially stretched OCT images.
   Translational Relevance: If accurate measurements are to be obtained, images with a native aspect ratio similar to microscopy must be used.
C1 [Uji, Akihito; Abdelfattah, Nizar Saleh; Balasubramanian, Siva; Lei, Jianqin; Sadda, SriniVas R.] Doheny Eye Inst, Doheny Image Reading Ctr, 1355 San Pablo St, Los Angeles, CA 90033 USA.
   [Uji, Akihito; Abdelfattah, Nizar Saleh; Balasubramanian, Siva; Lei, Jianqin; Sadda, SriniVas R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Boyer, David S.] Retina Vitreous Associates Med Grp, Beverly Hills, CA USA.
C3 Doheny Eye Institute; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA; Retina Vitreous
   Associates Medical Group
RP Sadda, SR (通讯作者)，Doheny Image Reading Ctr, 1355 San Pablo St,Suite 100, Los Angeles, CA 90033 USA.
EM ssadda@doheny.org
RI Abdelfattah, Nizar Saleh/H-6908-2019
OI Abdelfattah, Nizar Saleh/0000-0002-9396-3054
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NR 28
TC 6
Z9 6
U1 1
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD MAR
PY 2017
VL 6
IS 2
AR 1
DI 10.1167/tvst.6.2.1
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FH2GI
UT WOS:000410956600001
PM 28299239
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Chelala, E
   Arej, N
   Antoun, J
   Kourie, HR
   Zaarour, K
   Haddad, FG
   Farhat, F
   El Karak, F
   Kattan, J
AF Chelala, Elias
   Arej, Nicolas
   Antoun, Joelle
   Kourie, Hampig Raphael
   Zaarour, Karen
   Haddad, Fady Ghassan
   Farhat, Fadi
   El Karak, Fadi
   Kattan, Joseph
TI Central Macular Thickness Monitoring after a Taxane-Based Therapy in
   Visually Asymptomatic Patients
SO CHEMOTHERAPY
LA English
DT Article
DE Taxanes; Docetaxel; Paclitaxel; Central macular thickness; Cystoid
   macular edema; Optical coherence tomography
ID BOUND PACLITAXEL THERAPY; METASTATIC BREAST-CANCER; EDEMA SECONDARY;
   CLINICAL-EXPERIENCE; FLUID RETENTION; DOCETAXEL; MACULOPATHY;
   CHEMOTHERAPY; BEVACIZUMAB; TOXICITY
AB Background: Taxanes are drugs used in various chemotherapeutical protocols to treat solid tumors. They have multiple systemic adverse effects, such as bone marrow suppression, alopecia, nausea, and vomiting, and may rarely cause ocular symptoms. In the past decade, a few reported cases have shown the occurrence of a cystoid macular edema with significant visual loss after the use of a taxane-based chemotherapy. The aim of this study was to compare the central macular thickness (CMT) before and after the initiation of a taxane-based therapy in visually asymptomatic patients and to elucidate the possible impact of these drugs on the vision of cancer patients. Methods: Patients with a confirmed diagnosis of a solid tumor were screened for any ophthalmic disease before inclusion and had a baseline macular spectral domain optical coherence tomography (OCT; RT-Vue-100; Optovue Inc., Fremont, CA, USA) before the initiation of a taxane-based chemotherapy according to different protocols, such as 4EC-4T, 3FEC/3T, or 4TC. OCT was repeated after 4 cycles (or 3 months) of treatment, and CMT was compared to baseline. Patients presenting diabetic retinopathy, age-related macular degeneration or any condition that causes macular edema confirmed by ophthalmic examination were excluded. Results: Fifty eyes of 25 patients were included; 92% of the subjects were female with a mean age of 48.52 years, 88% were diagnosed with breast cancer, 8% with esophageal cancer, and 4% with ovarian cancer. Docetaxel was the taxane administered to 92% of the patients. The received dose of docetaxel ranged between 110 and 160 mg. The other patients had paclitaxel in their protocols. No significant macular edema or drop in visual acuity were noted in any patient. Nevertheless, the mean CMT was found to be increased, particularly in the parafoveal and perifoveal areas (mean difference of + 2.22 mu m; p = 0.001). Conclusion: Taxane-based chemotherapy regimens seem to increase macular thickness, with a relative sparing of the fovea, in patients without significant macular edema. Further research is required to better explain the pathophysiology and possible impact of this phenomenon. (C) 2017 S. Karger AG, Basel
C1 [Chelala, Elias; Arej, Nicolas; Antoun, Joelle; Zaarour, Karen] St Joseph Univ, Dept Ophthalmol, Fac Med, Beirut, Lebanon.
   [Kourie, Hampig Raphael; Haddad, Fady Ghassan; Farhat, Fadi; El Karak, Fadi; Kattan, Joseph] St Joseph Univ, Dept Oncol, Fac Med, Beirut, Lebanon.
C3 American University of Beirut
RP Kourie, HR (通讯作者)，St Joseph Univ, Dept Oncol, Fac Med, Beirut, Lebanon.
EM hampig.kourie@hotmail.com
RI Arej, Nicolas/V-8505-2019
OI Arej, Nicolas/0000-0003-0481-2228
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NR 40
TC 8
Z9 8
U1 0
U2 4
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0009-3157
EI 1421-9794
J9 CHEMOTHERAPY
JI Chemotherapy
PY 2017
VL 62
IS 3
BP 199
EP 204
DI 10.1159/000456653
PG 6
WC Oncology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Pharmacology & Pharmacy
GA ES8XH
UT WOS:000399839700010
PM 28351058
DA 2022-11-30
ER

PT J
AU Batioglu, F
   Demirel, S
   Ozmert, E
   Abdullayev, A
   Bilici, S
AF Batioglu, Figen
   Demirel, Sibel
   Ozmert, Emin
   Abdullayev, Ahmet
   Bilici, Serdar
TI Short-term outcomes of switching anti-VEGF agents in eyes with
   treatment-resistant wet AMD
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Aflibercept; Age-related macular degeneration; Ranibizumab
ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION;
   INTRAVITREAL RANIBIZUMAB; DOSING REGIMEN; TRAP-EYE; AFLIBERCEPT;
   BEVACIZUMAB; TACHYPHYLAXIS; MACROPHAGE; THERAPY
AB Background: To investigate the short-term outcomes of treatment with intravitreal aflibercept in cases with wet age-related macular degeneration (AMD) resistant to ranibizumab.
   Methods: The study included patients who had been undergoing follow-up for a minimum of three months at the Ankara University Faculty of Medicine Ophthalmology Department's Retina Unit with a diagnosis of wet AMD. All cases had received intravitreal aflibercept injection due to the presence of intraretinal/subretinal fluid and pigment epithelial detachment (PED), as detected by optical coherence tomography (OCT), despite having received intravitreal ranibizumab. Medical records of the cases were investigated retrospectively and the demographic data, treatments administered before aflibercept injection, best-corrected visual acuity (BCVA) before and after aflibercept injection, central macular thickness (CMT), and the presence of intraretinal/subretinal fluid and the height and presence of PED were recorded.
   Results: A total of 29 eyes from 11 females and 17 males were included in the study. The mean age was 73.89 +/- 7.49 (62-92). The average number of intraocular injections administered before aflibercept injection was 11.75 +/- 5.73 (6-25). The mean duration of follow-up following aflibercept injection was 4.55 +/- 2.14 (3-11) months, with a mean of 3.44 +/- 0.73 (3-5) aflibercept injections during this period. The mean BCVA values before and after aflibercept injection were found to be 0.83 and 0.77 LogMAR, respectively. The mean CMT values before and after aflibercept injection were 471.3 (97-1365) and 345.1 (97-585) microns, respectively (p < 0.001). The PED height before and after aflibercept injection was 350.4 +/- 151.7 (129-793) and 255.52 +/- 156.8 (0-528) microns, respectively (p < 0.05).
   Conclusion: Switching to intravitreal aflibercept appears to be an effective treatment modality for patients with AMD who are resistant to ranibizumab. While anatomic success including the effect of reducing the PED height was achieved in the short term following aflibercept injection in all cases, no concomitant increase in visual acuity occurred. This is attributed to the long-term presence of chronic fluid and the development of scar tissue before the treatment.
C1 [Batioglu, Figen; Demirel, Sibel; Ozmert, Emin; Abdullayev, Ahmet; Bilici, Serdar] Ankara Univ, Dept Ophthalmol, Fac Med, Vehbi Koc Goz Hastanesi, TR-06100 Ankara, Turkey.
C3 Ankara University
RP Batioglu, F (通讯作者)，Ankara Univ, Dept Ophthalmol, Fac Med, Vehbi Koc Goz Hastanesi, Mamak Caddesi, TR-06100 Ankara, Turkey.
EM drsibeldemireltr@yahoo.com.tr
RI Demirel, Sibel/AAQ-4282-2020; DEMIREL, SIBEL/GQH-3232-2022; Batıoğlu,
   Figen/AAQ-3727-2020
OI Demirel, Sibel/0000-0002-6430-6565; DEMIREL, SIBEL/0000-0002-2477-9974;
   Batıoğlu, Figen/0000-0002-5834-7512; Bilici, Serdar/0000-0003-1346-0850
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NR 30
TC 16
Z9 18
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD APR 11
PY 2015
VL 15
AR 40
DI 10.1186/s12886-015-0025-z
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CG5GK
UT WOS:000353318900001
PM 25885684
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Abdillahi, H
   Enzmann, V
   Wittwer, VV
   Wolf, S
   Wolf-Schnurrbusch, UEK
AF Abdillahi, Hannan
   Enzmann, Volker
   Wittwer, Valery V.
   Wolf, Sebastian
   Wolf-Schnurrbusch, Ute E. K.
TI Vitreoretinal Interface Changes in Geographic Atrophy
SO OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; FUNDUS AUTOFLUORESCENCE PATTERNS; MACULAR
   PIGMENT CAROTENOIDS; FACTOR-H POLYMORPHISM; VITREOMACULAR ADHESION;
   NLRP3 INFLAMMASOME; VISUAL-ACUITY; DEGENERATION; TRACTION; MACULOPATHY
AB Purpose: Geographic atrophy (GA) is the end-stage manifestation of atrophic age-related macular degeneration (AMD). The disease progresses slowly over time, eventually causing loss of central vision. Its cause and pathomechanism are not fully known. Previous studies have suggested that vitreoretinal traction (VRT) may contribute to the progression of neovascular AMD. The aim of this study was to examine whether an association between changes at the vitreoretinal interface (VRI), in particular traction (VRT), and the characteristics and progression of GA in eyes with dry AMD can be established.
   Design: Clinic-based prospective cohort study.
   Participants: A total of 97 patients (age range, 61-90 years; mean, 78.4 years) with GA secondary to dry AMD were enrolled. Patients exhibiting neovascular signs on fluorescein angiography in either eye were excluded.
   Methods: The VRI changes were examined using spectral-domain optical coherence tomography (SD-OCT). Characteristics of GA were examined using fundus autofluorescence (FAF) imaging. All imaging was performed using a Spectralis SLO+OCT device (Heidelberg Engineering, Heidelberg, Germany); GA area was measured using the Region Finder (Heidelberg Engineering) software native to the Spectralis platform.
   Main Outcome Measures: Area and increase in area of GA.
   Results: A total of 97 eyes were examined. Vitreoretinal traction was found in 39 eyes (40%). The GA area at baseline was 6.65 +/- 5.64 mm(2) in eyes with VRT and 5.73 +/- 4.72 mm(2) in eyes with no VRT. The annual rate of progression of GA area progression was 2.99 +/- 0.66 mm(2) in eyes with VRT and 1.45 +/- 0.67mm(2) in eyes without VRT. Differences between groups in both parameters were statistically significant (n = 97 total number of eyes; P<0.001). Multiple regression analysis confirmed this finding (B = 0.714, P<0.001; F-3,F-93 = 72.542, P<0.001; adjusted R-2 = 0.691)
   Conclusions: Our results indicate an association between VRT and an increased rate of progression of GA area in dry AMD. Monitoring VRT may contribute to an improved estimate of the prospective time of visual loss and to a better timing of emerging therapies in dry AMD. (C) 2014 by the American Academy of Ophthalmology.
C1 [Abdillahi, Hannan; Wolf, Sebastian; Wolf-Schnurrbusch, Ute E. K.] Inselspital Bern, Dept Ophthalmol, Univ Hosp, Bern Photog Reading Ctr, CH-3010 Bern, Switzerland.
   [Abdillahi, Hannan; Enzmann, Volker; Wittwer, Valery V.; Wolf, Sebastian; Wolf-Schnurrbusch, Ute E. K.] Univ Bern, Bern, Switzerland.
   [Enzmann, Volker; Wittwer, Valery V.; Wolf, Sebastian; Wolf-Schnurrbusch, Ute E. K.] Inselspital Bern, Dept Ophthalmol, Univ Hosp, CH-3010 Bern, Switzerland.
C3 University of Bern; University Hospital of Bern; University of Bern;
   University of Bern; University Hospital of Bern
RP Wolf-Schnurrbusch, UEK (通讯作者)，Inselspital Bern, Dept Ophthalmol, CH-3010 Bern, Switzerland.
EM ute.wolf@insel.ch
RI Mitchell, Paul/P-1498-2014; Wolf, Sebastian/B-8782-2008
OI Wolf, Sebastian/0000-0002-7467-7028; Enzmann, Volker/0000-0003-4384-4855
FU Novartis; Alcon; Roche; Bayer; Optos Inc.; Heidelberg Engineering;
   Allergan; Heidelberg; Velux
FX S.W. received support from Novartis, Alcon, Roche, Bayer, Optos Inc.,
   and Heidelberg Engineering. U.E.K.W-S. received an unrestricted grant
   from Novartis and sponsorship of other studies from Alcon, Allergan,
   Novartis, Heidelberg, and Velux. These sponsors had no role in the
   design or conduct of this research.
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NR 39
TC 6
Z9 6
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD SEP
PY 2014
VL 121
IS 9
BP 1734
EP 1739
DI 10.1016/j.ophtha.2014.03.036
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AO2KY
UT WOS:000341151800023
PM 24863462
DA 2022-11-30
ER

PT J
AU Binder, S
   Stanzel, BV
   Krebs, I
   Glittenberg, C
AF Binder, Susanne
   Stanzel, Boris V.
   Krebs, Ilse
   Glittenberg, Carl
TI Transplantation of the RPE in AMD
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
ID RETINAL-PIGMENT EPITHELIUM; AGE-RELATED MACULOPATHY; ENDOTHELIAL
   GROWTH-FACTOR; GLYCATION END-PRODUCTS; SUBFOVEAL CHOROIDAL
   NEOVASCULARIZATION; ROD OUTER SEGMENTS; MACULAR TRANSLOCATION SURGERY;
   ANTERIOR LENS CAPSULE; FACTOR-H POLYMORPHISM; HUMAN BRUCHS MEMBRANE
AB The retinal pigment epithelium (RPE) maintains retinal function as the metabolic gatekeeper between photoreceptors (PRs) and the choriocapillaries. The RPE and Bruch's membrane (BM) suffer cumulative damage over lifetime, which is thought to induce age-related macular degeneration (AMD) in susceptible individuals. Unlike palliative pharmacologic treatments, replacement of the RPE has a curative potential for AMD.
   This article reviews mechanisms leading to RPE dysfunction in aging and AMD, laboratory studies on RPE transplantation, and surgical techniques used in AMD patients. Future strategies using ex vivo steps prior to transplantation, BM prosthetics, and stem cell applications are discussed.
   The functional peculiarity of the macular region, epigenetic phenomena leading to an age-related shift in protein expression, along with the accumulation of lipofuscin may affect the metabolism in the central RPE. Thickening of BM with age decreases its hydraulic conductivity. Drusen are deposits of extracellular material and formed in part by activation of the alternative complement pathway in individuals carrying a mutant allele of complement factor H.
   AMD likely represents an umbrella term for a disease entity with multifactorial etiology and manifestations. Presently, a slow progressing (dry) non-neovascular atrophic form and a rapidly blinding neovascular (wet) form are discerned. No therapy is currently available for the former, while RPE transplantation and promising (albeit non-causal) anti-angiogenic therapies are available for the latter.
   The potential of RPE transplantation was demonstrated in animal models. Rejection of allogeneic homologous transplants in patients focused further studies on autologous sources. In vitro studies elucidated cell adhesion and wound healing mechanisms on aged human 13M. Currently. autologous RPE, harvested from the midperiphery, is being transplanted as a cell suspension or a patch of RPE and choroid in AMD patients. These techniques have been evaluated from several groups.
   Autologous RPE transplants may have the disadvantage of carrying the same genetic information that may have led to AMD manifestation. An intermittent culturing step Would allow for in vitro therapy of the RPE, its rejuvenation and prosthesis of BM to improve the success RPE transplants. Recent advances in stem cell biology when combined with lessons learned from studies of RPE transplantation are intriguing future therapeutic modalities for AMD patients. (C) 2007 Elsevier Ltd. All rights reserved.
C1 Hosp City Vienna, Rudolf Fdn Clin, Dept Ophthalmol, Vienna, Austria.
   Ludwig Boltzman Inst Retinol & Biomicroscop Laser, Vienna, Austria.
   Stanford Univ, Sch Med, Dept Ophthalmol, Stanford, CA 94305 USA.
C3 Ludwig Boltzmann Institute; Stanford University
RP Binder, S (通讯作者)，Hosp City Vienna, Rudolf Fdn Clin, Dept Ophthalmol, Vienna, Austria.
EM susanne.binder@wienkav.at
RI Stanzel, Boris/AAG-7010-2022; Stanzel, Boris/ADP-9221-2022
OI Stanzel, Boris/0000-0002-4316-1539; Stanzel, Boris/0000-0002-4316-1539
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NR 607
TC 218
Z9 238
U1 0
U2 38
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD SEP
PY 2007
VL 26
IS 5
BP 516
EP 554
DI 10.1016/j.preteyeres.2007.02.002
PG 39
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 219OY
UT WOS:000250095700004
PM 17532250
DA 2022-11-30
ER

PT J
AU Ma, WC
   Lee, SE
   Guo, JC
   Qu, W
   Hudson, BI
   Schmidt, AM
   Barile, GR
AF Ma, Wanchao
   Lee, Song Eun
   Guo, Jiancheng
   Qu, Wu
   Hudson, Barry I.
   Schmidt, Ann Marie
   Barile, Gaetano R.
TI RAGE ligand upregulation of VEGF secretion in ARPE-19 cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID GLYCATION END-PRODUCTS; ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION;
   CHOROIDAL NEOVASCULARIZATION; CYSTEINE RESIDUES; INFLAMMATORY RESPONSES;
   MEDIATED EXPRESSION; NEURITE OUTGROWTH; NERVOUS-SYSTEM; RECEPTOR
AB PURPOSE. The importance of VEGF in stimulating neovascular age-related macular degeneration (AMD) is well-recognized, but the initiating factors that induce local upregulation of VEGF remain unclear. The current study was conducted to test the hypothesis that activation of RAGE (receptor for advanced glycation end products [AGES]) by its ligands, including AGES, amyloid-P peptide (A beta), and S100B/calgranulins, some of which are known components of drusen and Bruch's membrane deposits, modulate secretion of VEGF by retinal pigment epithelial (RPE) cells.
   METHODS. ARPE-19 cells were used for all experiments. The cells were transfected with constructs encoding a signal transduction mutant of human RAGE to assess the RAGE-dependence of intracellular signaling. VEGF secretion and gene expression were assessed by ELISA and quantitative real-time PCR. SDS-PAGE and size exclusion chromatography were performed to analyze the structural changes of S100B after oxidation of its thiol groups under denaturing and nondenaturing conditions, respectively. NF-kappa B activation was assessed via electrophoretic mobility shift assay (EMSA). The impact of the NF-kappa B inhibition was assessed by using parthenolide.
   RESULTS. ARPE-19 cells basally secreted VEGF under normal cell culture conditions. Immobilized ligands of RAGE increased EGF secretion in a RAGE-dependent manner. In contrast, soluble AGE-BSA, fresh A beta, and S100B were less effective in increasing VEGF secretion. Studies with A beta demonstrated that oligomeric and surface-immobilized forms of A beta, but not soluble monomeric forms of A beta, were effective upregulators of VEGF secretion Via RAGE. Oxidation of S100B's thiol groups resulted in the formation of oligomers that displayed distinct RAGE biological activity compared with the simple dimeric form. RAGE-mediated upregulation of VEGF secretion by ARPE-19 cells was largely dependent on NF-kappa B, as indicated by studies with parthenolide.
   CONCLUSIONS. Immobilized or oligomerized ligands for RAGE induce R-PE cells to increase VEGF secretion. NF-kappa B plays a central role in RAGE-dependent RPE secretion of VEGF. In AMD. activation of the RAGE axis in RPE cells may contribute to upregulation of VEGF, potentially inciting or propagating neovascular macular disease.
C1 Columbia Univ, Coll Phys & Surg, Dept Ophthalmol, New York, NY USA.
   Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY USA.
C3 Columbia University; Columbia University
RP Barile, GR (通讯作者)，Harkness Eye Inst, 635 W 165th St,Box 94, New York, NY 10032 USA.
EM grb17@columbia.edu
RI Hudson, Barry/B-3122-2009
OI Hudson, Barry/0000-0001-7647-8121
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NR 27
TC 85
Z9 92
U1 0
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2007
VL 48
IS 3
BP 1355
EP 1361
DI 10.1167/iovs.06-0738
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 142YF
UT WOS:000244686500054
PM 17325184
DA 2022-11-30
ER

PT J
AU McGuinness, MB
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   Karahalios, A
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   Simpson, JA
AF McGuinness, Myra B.
   Kasza, Jessica
   Karahalios, Amalia
   Guymer, Robyn H.
   Finger, Robert P.
   Simpson, Julie A.
TI A comparison of methods to estimate the survivor average causal effect
   in the presence of missing data: a simulation study
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
DE Causal inference; Death; Iron; Macular degeneration; Missing data;
   Principal stratification; Sensitivity analysis; Simulation study;
   Survival bias; Unmeasured confounding
ID MARGINAL STRUCTURAL MODELS; PRINCIPAL-STRATIFICATION; MACULAR
   DEGENERATION; PROPENSITY SCORE; SENSITIVITY-ANALYSIS; INFERENCE; IRON;
   OUTCOMES; TUTORIAL; DROPOUT
AB Background: Attrition due to death and non-attendance are common sources of bias in studies of age-related diseases. A simulation study is presented to compare two methods for estimating the survivor average causal effect (SACE) of a binary exposure (sex-specific dietary iron intake) on a binary outcome (age-related macular degeneration, AMD) in this setting.
   Methods: A dataset of 10,000 participants was simulated 1200 times under each scenario with outcome data missing dependent on measured and unmeasured covariates and survival. Scenarios differed by the magnitude and direction of effect of an unmeasured confounder on both survival and the outcome, and whether participants who died following a protective exposure would also die if they had not received the exposure (validity of the monotonicity assumption). The performance of a marginal structural model (MSM, weighting for exposure, survival and missing data) was compared to a sensitivity approach for estimating the SACE. As an illustrative example, the SACE of iron intake on AMD was estimated using data from 39,918 participants of the Melbourne Collaborative Cohort Study.
   Results: The MSM approach tended to underestimate the true magnitude of effect when the unmeasured confounder had opposing directions of effect on survival and the outcome. Overestimation was observed when the unmeasured confounder had the same direction of effect on survival and the outcome. Violation of the monotonicity assumption did not increase bias. The estimates were similar between the MSM approach and the sensitivity approach assessed at the sensitivity parameter of 1 (assuming no survival bias). In the illustrative example, high iron intake was found to be protective of AMD (adjusted OR 0.57, 95% CI 0.40-0.82) using complete case analysis via traditional logistic regression. The adjusted SACE odds ratio did not differ substantially from the complete case estimate, ranging from 0.54 to 0.58 for each of the SACE methods.
   Conclusions: On average, MSMs with weighting for exposure, missing data and survival produced biased estimates of the SACE in the presence of an unmeasured survival-outcome confounder. The direction and magnitude of effect of unmeasured survival-outcome confounders should be considered when assessing exposure-outcome associations in the presence of attrition due to death.
C1 [McGuinness, Myra B.; Guymer, Robyn H.] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [McGuinness, Myra B.; Karahalios, Amalia; Simpson, Julie A.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
   [Kasza, Jessica] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3010, Australia.
   [Guymer, Robyn H.] Univ Melbourne, Dept Surg, Ophthalmol, Melbourne, Vic, Australia.
   [Finger, Robert P.] Univ Bonn, Dept Ophthalmol, Bonn, Germany.
   [Simpson, Julie A.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; Monash University; University of Melbourne;
   University of Bonn; Cancer Council Victoria
RP McGuinness, MB (通讯作者)，Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.; McGuinness, MB (通讯作者)，Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
EM myra.mcguinness@unimelb.edu.au
RI McGuinness, Myra/G-4900-2017
OI McGuinness, Myra/0000-0002-5422-040X
FU VicHealth; Cancer Council Victoria; National Health & Medical Research
   Council of Australia (NHMRC) [209057, 251533, 396414]; Ophthalmic
   Research Institute of Australia; American Health Assistance Foundation
   [M2008-082]; Jack Brockhoff Foundation; John Reid Charitable Trust;
   Australian Government Research Training Program Scheme; Victorian Centre
   for Biostatistics (NHMRC: Centre of Research Excellence) [1035261];
   National Health and Medical Research Council (NHMRC) [1104975]; NHMRC
   [1103013]
FX Melbourne Collaborative Cohort Study recruitment was funded by VicHealth
   and Cancer Council Victoria. Further Melbourne Collaborative Cohort
   Study funding: the National Health & Medical Research Council of
   Australia (NHMRC) Program Grant 209057, Capacity Building Grant 251533
   and Enabling Grant 396414. The ophthalmic component was funded by the
   Ophthalmic Research Institute of Australia; American Health Assistance
   Foundation (M2008-082), Jack Brockhoff Foundation, John Reid Charitable
   Trust, Perpetual Trustees. M. McGuinness is funded by the Australian
   Government Research Training Program Scheme and a studentship courtesy
   of Victorian Centre for Biostatistics (NHMRC: Centre of Research
   Excellence grant 1035261). J. Simpson is funded by a National Health and
   Medical Research Council (NHMRC) Senior Research Fellowship 1104975, and
   R. Guymer by a NHMRC Principal Research Fellowship 1103013. This work
   was supported by infrastructure from the Cancer Council of Victoria.
   CERA receives operational infrastructure support from the Victorian
   government. The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
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NR 54
TC 4
Z9 4
U1 0
U2 6
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD DEC 3
PY 2019
VL 19
IS 1
AR 223
DI 10.1186/s12874-019-0874-x
PG 14
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA KH7SC
UT WOS:000510848900003
PM 31795945
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Coroniti, R
   Farjo, R
   Nuno, DJ
   Otvos, L
   Scolaro, L
   Surmacz, E
AF Coroniti, Roberta
   Farjo, Rafal
   Nuno, Didier J.
   Otvos, Laszlo
   Scolaro, Laura
   Surmacz, Eva
TI Designer Leptin Receptor Antagonist Allo-aca Inhibits VEGF Effects in
   Ophthalmic Neoangiogenesis Models
SO FRONTIERS IN MOLECULAR BIOSCIENCES
LA English
DT Article
DE leptin; ObR antagonist; peptide drug; VEGF; ocular neoangiogenesis
ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER; VITREOUS LEPTIN; ANGIOGENESIS;
   EXPRESSION; PATHWAYS; TARGETS; CELLS
AB Experimental and clinical data suggest that pro-angiogenic, pro-inflammatory and mitogenic cytokine leptin can be implicated in ocular neovascularization and other eye pathologies. At least in part, leptin action appears to be mediated through functional interplay with vascular endothelial growth factor (VEGF). VEGF is a potent regulator of neoangiogenesis and vascular leakage with a proven role in conditions such as proliferative diabetic retinopathy, age-related macular degeneration and diabetic macular edema. Accordingly, drugs targeting VEGF are becoming mainstream treatments for these diseases. The crosstalk between leptin and VEGF has been noted in different tissues, but its involvement in the development of eye pathologies is unclear. Leptin is coexpressed with VEGF during ocular neovascularization and can potentiate VEGF synthesis and angiogenic function. However, whether or not VEGF regulates leptin expression or signaling has never been studied. Consequently, we addressed this aspect of leptin/VEGF crosstalk in ocular models, focusing on therapeutic exploration of underlying mechanisms. Here we show, for the first time, that in retinal (RF/6A) and corneal (BCE) endothelial cells, VEGF (100 ng/mL, 24 h) stimulated leptin mRNA synthesis by 70 and 30%, respectively, and protein expression by 56 and 28%, respectively. In parallel, VEGF induced RF/6A and BCE cell growth by 33 and 20%, respectively. In addition, VEGF upregulated chemotaxis and chemokinesis in retinal cells by similar to 40%. VEGF-dependent proliferation and migration were significantly reduced in the presence of the leptin receptor antagonist, Allo-aca, at 100-250 nmol/L concentrations. Furthermore, Allo-aca suppressed VEGF-dependent long-term (24 h), but not acute (15 min) stimulation of the Akt and ERK1/2 signaling pathways. The efficacy of Allo-aca was validated in the rat laser-induced choroidal neovascularization model where the compound (5 mu g/eye) significantly reduced pathological vascularization with the efficacy similar to that of a standard treatment (anti-VEGF antibody, 1 mu g/eye). Cumulatively, our results suggest that chronic exposure to VEGF upregulates leptin expression and function. As leptin can in turn activate VEGF, the increased abundance of both cytokines could amplify pro-angiogenic and pro-inflammatory environement in the eye. Thus, combined therapies targeting ObR and VEGF should be considered in the treatment of ocular diseases.
C1 [Coroniti, Roberta; Scolaro, Laura; Surmacz, Eva] Temple Univ, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA.
   [Farjo, Rafal; Nuno, Didier J.] Temple Univ, Dept Biol, Philadelphia, PA 19122 USA.
   [Otvos, Laszlo] EyeCRO, Oklahoma City, OK USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple
   University; Pennsylvania Commonwealth System of Higher Education
   (PCSHE); Temple University
RP Surmacz, E (通讯作者)，Temple Univ, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA.
EM surmacz@temple.edu
FU Novo Nordisk Diabetes Innovation Program
FX This study was supported in part by a research grant from Novo Nordisk
   Diabetes Innovation Program to ES.
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NR 49
TC 5
Z9 5
U1 0
U2 0
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 2296-889X
J9 FRONT MOL BIOSCI
JI Front. Mol. Biosci.
PY 2016
VL 3
AR 67
DI 10.3389/fmolb.2016.00067
PG 10
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA VH8CX
UT WOS:000455328600067
PM 27790618
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Korbolina, EE
   Ershov, NI
   Bryzgalov, LO
   Kolosova, NG
AF Korbolina, Elena E.
   Ershov, Nikita I.
   Bryzgalov, Leonid O.
   Kolosova, Natalia G.
TI Application of quantitative trait locus mapping and transcriptomics to
   studies of the senescence-accelerated phenotype in rats
SO BMC GENOMICS
LA English
DT Article
ID AMD-LIKE RETINOPATHY; TARGETED ANTIOXIDANT SKQ1; ALZHEIMERS-DISEASE;
   MACULAR DEGENERATION; GENE-EXPRESSION; MOUSE MODELS; C/EBP-GAMMA; OXYS
   RATS; RETINAL DEGENERATION; CATARACT DEVELOPMENT
AB Background: Etiology of complex disorders, such as cataract and neurodegenerative diseases including age-related macular degeneration (AMD), remains poorly understood due to the paucity of animal models, fully replicating the human disease. Previously, two quantitative trait loci (QTLs) associated with early cataract, AMD-like retinopathy, and some behavioral aberrations in senescence-accelerated OXYS rats were uncovered on chromosome 1 in a cross between OXYS and WAG rats. To confirm the findings, we generated interval-specific congenic strains, WAG/OXYS-1.1 and WAG/OXYS-1.2, carrying OXYS-derived loci of chromosome 1 in the WAG strain. Both congenic strains displayed early cataract and retinopathy but differed clinically from OXYS rats. Here we applied a high-throughput RNA sequencing (RNA-Seq) strategy to facilitate nomination of the candidate genes and functional pathways that may be responsible for these differences and can contribute to the development of the senescence-accelerated phenotype of OXYS rats.
   Results: First, the size and map position of QTL-derived congenic segments were determined by comparative analysis of coding single-nucleotide polymorphisms (SNPs), which were identified for OXYS, WAG, and congenic retinal RNAs after sequencing. The transferred locus was not what we expected in WAG/OXYS-1.1 rats. In rat retina, 15442 genes were expressed. Coherent sets of differentially expressed genes were identified when we compared RNA-Seq retinal profiles of 20-day-old WAG/OXYS-1.1, WAG/OXYS-1.2, and OXYS rats. The genes most different in the average expression level between the congenic strains included those generally associated with the Wnt, integrin, and TGF-beta signaling pathways, widely involved in neurodegenerative processes. Several candidate genes (including Arhgap33, Cebpg, Gtf3c1, Snurf, Tnfaip3, Yme1l1, Cbs, Car9 and Fn1) were found to be either polymorphic in the congenic loci or differentially expressed between the strains. These genes may contribute to the development of cataract and retinopathy.
   Conclusions: This study is the first RNA-Seq analysis of the rat retinal transcriptome generated with 40 mln sequencing read depth. The integration of QTL and transcriptomic analyses in our study forms the basis of future research into the relationship between the candidate genes within the congenic regions and specific changes in the retinal transcriptome as possible causal mechanisms that underlie age-associated disorders.
C1 [Korbolina, Elena E.; Ershov, Nikita I.; Bryzgalov, Leonid O.; Kolosova, Natalia G.] RAS, Inst Cytol & Genet, SB, Novosibirsk, Russia.
   [Korbolina, Elena E.; Bryzgalov, Leonid O.; Kolosova, Natalia G.] Novosibirsk State Univ, Novosibirsk 630090, Russia.
C3 Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB
   RAS; Novosibirsk State University
RP Korbolina, EE (通讯作者)，RAS, Inst Cytol & Genet, SB, Novosibirsk, Russia.
EM lungry@bionet.nsc.ru
RI Kolosova, Nataliya G/AAR-7409-2020; Kolosova, Nataliya G/P-3178-2015;
   Ershov, Nikita/F-7484-2017
OI Kolosova, Nataliya G/0000-0003-2398-8544; Kolosova, Nataliya
   G/0000-0003-2398-8544; Ershov, Nikita/0000-0003-3423-3497
FU Ministry of Education and Science of the Russian Federation; Grants of
   the Government of the Russian Federation [2012-220-03-435,
   14.B25.31.0033]
FX This work was supported by the Ministry of Education and Science of the
   Russian Federation and partially (when regards to instrumental high
   throughput sequencing) by Grants of the Government of the Russian
   Federation N 2012-220-03-435 and N 14.B25.31.0033. The computations were
   performed at the Siberian Supercomputer Center SB RAS (Novosibirsk,
   Russia). We wish to thank the Breeding Experimental Animal Laboratory of
   the Institute of Cytology and Genetics, SB RAS (Novosibirsk, Russia) for
   their care and maintenance of the experimental animals used in this
   study. The study was conducted in the Center for Genetic Resources of
   Laboratory Animals ICG SB RAS (RFMEFI61914X0005).
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NR 160
TC 6
Z9 6
U1 0
U2 12
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD DEC 19
PY 2014
VL 15
SU 12
AR S3
DI 10.1186/1471-2164-15-S12-S3
PG 17
WC Biotechnology & Applied Microbiology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CH4CI
UT WOS:000353978600003
PM 25563673
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Yehoshua, Z
   Gregori, G
   Sadda, SR
   Penha, FM
   Goldhardt, R
   Nittala, MG
   Konduru, RK
   Feuer, WJ
   Gupta, P
   Li, Y
   Rosenfeld, PJ
AF Yehoshua, Zohar
   Gregori, Giovanni
   Sadda, SriniVas R.
   Penha, Fernando M.
   Goldhardt, Raquel
   Nittala, Muneeswar G.
   Konduru, Ranjith K.
   Feuer, William J.
   Gupta, Pooja
   Li, Ying
   Rosenfeld, Philip J.
TI Comparison of Drusen Area Detected by Spectral Domain Optical Coherence
   Tomography and Color Fundus Imaging
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE drusen; age-related macular degeneration; optical coherence tomography;
   color fundus photography; imaging
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; SEVERITY SCALE; GRADING
   SYSTEM; SD-OCT; RISK; PHOTOGRAPHS; PERFORMANCE; DISEASE; IMAGES
AB PURPOSE. To compare the measurements of drusen area from manual segmentation of color fundus photographs with those generated by an automated algorithm designed to detect elevations of the retinal pigment epithelium (RPE) on spectral domain optical coherence tomography (SD-OCT) images.
   METHODS. Fifty eyes with drusen secondary to nonexudative age-related macular degeneration were enrolled. All eyes were imaged with a high-definition OCT instrument using a 200 3 200 A-scan raster pattern covering a 6 mm X 6 mm area centered on the fovea. Digital color fundus images were taken on the same day. Drusen were traced manually on the fundus photos by graders at the Doheny Image Reading Center, whereas quantitative OCT measurements of drusen were obtained by using a fully automated algorithm. The color fundus images were registered to the OCT data set and measurements within corresponding 3- and 5-mm circles centered at the fovea were compared.
   RESULTS. The mean areas (+/- SD [range]) for the 3-mm circles were SD-OCT 1.57 (+/- 1.08 [0.03-4.44]); 3-mm color fundus 1.92 (+/- 1.08 [0.20-3.95]); 5-mm SD-OCT 2.12 (+/- 1.55 [0.03-5.40]); and 5-mm color fundus 3.38 (+/- 1.90 [0.39-7.49]). The mean differences between color images and the SD-OCT (color - SD-OCT) were 0.36 (+/- 0.93) (P = 0.008) for the 3-mm circle and 1.26 (+/- 1.38) (P < 0.001) for the 5-mm circle measurements. Intraclass correlation coefficients of agreements for 3-and 5-mm measurements were 0.599 and 0.540, respectively.
   CONCLUSIONS. There was only fair agreement between drusen area measurements obtained from SD-OCT images and color fundus photos. Drusen area measurements on color fundus images were larger than those with SD-OCT scans. This difference can be attributed to the fact that the OCT algorithm defines drusen in terms of RPE deformations above a certain threshold, and will not include small, flat drusen and subretinal drusenoid deposits. The two approaches provide complementary information about drusen.
C1 [Yehoshua, Zohar; Gregori, Giovanni; Penha, Fernando M.; Goldhardt, Raquel; Feuer, William J.; Gupta, Pooja; Li, Ying; Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Sadda, SriniVas R.; Nittala, Muneeswar G.; Konduru, Ranjith K.] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA.
C3 Bascom Palmer Eye Institute; University of Miami; Doheny Eye Institute;
   University of Southern California
RP Rosenfeld, PJ (通讯作者)，Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
EM prosenfeld@med.miami.edu
RI Nittala, Muneeswar/AAT-7533-2020
FU Carl Zeiss Meditec, Inc.; Dublin, California; National Eye Institute
   Core Center [P30 EY014801]; Jerome A. Yavitz Charitable Foundation;
   Macula Vision Research Foundation; Emma Clyde Hodge Memorial Foundation;
   Florman Family Foundation Inc.; Gemcon Family Foundation; Research to
   Prevent Blindness, Inc.; NATIONAL EYE INSTITUTE [P30EY014801] Funding
   Source: NIH RePORTER
FX Supported in part by a grant from Carl Zeiss Meditec, Inc., Dublin,
   California; an unrestricted grant from Research to Prevent Blindness,
   Inc.; National Eye Institute Core Center Grant P30 EY014801 to the
   University of Miami; the Jerome A. Yavitz Charitable Foundation; the
   Macula Vision Research Foundation; the Emma Clyde Hodge Memorial
   Foundation; the Florman Family Foundation Inc.; and the Gemcon Family
   Foundation.
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NR 30
TC 24
Z9 24
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2013
VL 54
IS 4
BP 2429
EP 2434
DI 10.1167/iovs.12-11569
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 156KV
UT WOS:000319821700003
PM 23471895
OA Green Published
DA 2022-11-30
ER

PT J
AU Forrester, JV
   Lumsden, L
   Duncan, L
   Dick, AD
AF Forrester, JV
   Lumsden, L
   Duncan, L
   Dick, AD
TI Choroidal dendritic cells require activation to present antigen and
   resident choroidal macrophageS potentiate this response
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID II-POSITIVE CELLS; COLONY-STIMULATING FACTOR; PIGMENT EPITHELIAL-CELLS;
   BLOOD-RETINA BARRIER; IN-VIVO; ALVEOLAR MACROPHAGES; IFN-GAMMA;
   IMMUNOSUPPRESSIVE ACTIVITY; AUTOIMMUNE UVEORETINITIS; MACULAR
   DEGENERATION
AB Background/aim: The uveal compartment of the eye contains extensive networks of resident macrophages and dendritic cells. These cells are now recognised to have a role in many ocular pathologies. The aim of this study was to isolate, characterise, and compare the function of ciliary body/choroid dendritic cells and macrophages from the normal eye.
   Methods: Explants of rat and human ciliary body/choroid were cultured in vitro for various periods of time and cells harvested either from the supernatant fluid or from enzyme digested and washed explants. The cells were then phencityped by microscopy and flow cytometry, examined by video time lapse photomicroscopy, and analysed functionally in a series of immunciassays. IImid
   Results: Two main types of dendritic cell were identified: large veil-like MHC class motile but relatively non-translocatory cells and small MHC class IIhi motile and rapidly translocating cells. Tissue macrophages mainly remained associated with the explants in culture but gradually lost their resident tissue marker (ED2) and detached from the explants as clusters of low density, large, CR3 (ED7)(+) cells, some of which underwent apoptosis. Video time lapse studies showed dendritic cells constantly interacting with large single cells and cell clusters by traversing the interstices of the cell clusters. In functional studies, freshly isolated dendritic cells were poor presenters of antigen and required activation by short term culture for acquisition of antigen presenting function. In contrast, dendritic cell depleted choroidal cell preparations containing macrophages and other cells failed to present antigen even after short term culture but augmented the antigen presenting function of dendritic cells when tested in co-culture.
   Conclusion: At least two types of dendritic cells are present in the normal ciliary body/choroid layer of the eye. It is likely that these cells have different functions based on their motility and potential to migrate to secondary lymphoid tissue either during normal physiological homeostatic processes or during an inflammatory response. The behaviour of resident tissue myeloid cells may decide the outcome of the organism's response to stress, foreign antigen, and ageing processes such as age related macular degeneration.
C1 Univ Aberdeen, Sch Med, Dept Ophthalmol, Aberdeen AB9 2ZD, Scotland.
   Univ Bristol, Div Ophthalmol, Bristol BS8 1TH, Avon, England.
C3 University of Aberdeen; University of Bristol
RP Forrester, JV (通讯作者)，Univ Aberdeen, Sch Med, Dept Ophthalmol, Aberdeen AB9 2ZD, Scotland.
EM j.forrester@abdn.ac.uk
OI Dick, Andrew/0000-0002-0742-3159
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NR 41
TC 13
Z9 14
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAR
PY 2005
VL 89
IS 3
BP 369
EP 377
DI 10.1136/bjo.2004.054197
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 902KF
UT WOS:000227353900026
PM 15722321
OA Green Submitted, Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Schmidt-Erfurth, UM
   Elsner, H
   Terai, N
   Benecke, A
   Dahmen, G
   Michels, SM
AF Schmidt-Erfurth, UM
   Elsner, H
   Terai, N
   Benecke, A
   Dahmen, G
   Michels, SM
TI Effects of verteporfin therapy on central visual field function
SO OPHTHALMOLOGY
LA English
DT Article
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; SCANNING LASER OPHTHALMOSCOPE;
   INDOCYANINE GREEN ANGIOGRAPHY; PHOTODYNAMIC THERAPY; MACULAR
   DEGENERATION; IMPAIRMENT; MICROPERIMETRY; PHOTOCOAGULATION; SENSITIVITY;
   POPULATION
AB Purpose: To evaluate the effect of photodynamic therapy with verteporfin on the maintenance of central visual field function.
   Design: Randomized controlled clinical trial.
   Participants: Forty-six consecutive patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration including a classic component were randomly assigned. Thirty-three participants received standard verteporfin therapy, and 13 received placebo and laser treatment.
   Methods: The trial was performed as a single-center, double-masked study. Patients were examined before therapy and continuously in 3-month intervals during 2 years of follow-up. A scanning laser ophthalmoscope (SLO) was used to perform macular microperimetry. Absolute and relative scotomas were documented at each visit, and size was measured in square millimeters.
   Main Outcome Measures: The change in size of central scotoma in the verteporfin group compared with the placebo group.
   Results: An absolute scotoma was seen in 88%, and a relative scotoma was seen in 100% of eyes before therapy. Absolute defects were associated with the classic CNV component localized angiographically. In the verteporfin group, the absolute scotoma grew from 2.5 mm(2) at baseline to a final size of 7.3 mm(2) at month 24. In the placebo group, the mean lesion size of the absolute scotoma enlarged from an initial size of 2.7 mm(2) to 31.5 mm(2) after 24 months. The relative scotoma increased from 7.9 mm(2) at baseline to 20.8 mm(2) at month 24 in the verteporfin group, whereas a progression from 8.5 mm(2) initially to 48.3 mm(2) at the final presentation was measured in the placebo group. Statistical analysis showed that both the mean absolute and relative scotoma sizes were significantly smaller in the verteporfin group than the placebo group for all intervals from 6 to 24 months (P<0.001).
   Conclusions: Documentation of macular function with SLO perimetry demonstrated a significant benefit of verteporfin therapy for the preservation of the central visual field. Absolute and relative scotoma sizes remained smaller after therapy. This may influence reading ability and visual rehabilitation. Ophthalmology 2004;111: 931-939 (C) 2004 by the American Academy of Ophthalmology.
C1 Univ Schleswig Holstein, Dept Ophthalmol, Lubeck, Germany.
   Univ Schleswig Holstein, Dept Biomed Stat, Lubeck, Germany.
C3 University of Kiel; Schleswig Holstein University Hospital; University
   of Kiel; Schleswig Holstein University Hospital
RP Schmidt-Erfurth, UM (通讯作者)，Univ Lubeck, Dept Ophthalmol, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
CR Arnold J, 2001, AM J OPHTHALMOL, V131, P541
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NR 34
TC 44
Z9 51
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAY
PY 2004
VL 111
IS 5
BP 931
EP 939
DI 10.1016/j.ophtha.2003.12.025
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 818FR
UT WOS:000221231500014
PM 15121371
DA 2022-11-30
ER

PT J
AU Chen, L
   Dentchev, T
   Wong, R
   Hahn, P
   Wen, R
   Bennett, J
   Dunaief, JL
AF Chen, L
   Dentchev, T
   Wong, R
   Hahn, P
   Wen, R
   Bennett, J
   Dunaief, JL
TI Increased expression of ceruloplasmin in the retina following photic
   injury
SO MOLECULAR VISION
LA English
DT Article
ID MACULAR DEGENERATION; GENE-EXPRESSION; IRON TRANSPORT; AGE PIGMENT; RAT
   RETINA; MOUSE; ACERULOPLASMINEMIA; DEFICIENCY; PROTEINS; LIGHT
AB Purpose: Oxidative stress plays a role in the photic injury model of retinal degeneration and in age-related macular degeneration. Our preliminary microarray analysis of retinal gene expression upon photic injury suggested increased expression of ceruloplasmin, a ferroxidase that could reduce retinal oxidative stress. Patients with acerul oplasminemia have retinal degeneration, indicating that ceruloplasmin is necessary for maintenance of retinal health. The purpose of this study was to determine whether retinal ceruloplasmin is upregulated following photo-oxidation, to localize ceruloplasmin protein, and to determine which ceruloplasmin isoform is present in the retina.
   Methods: Balb/c mice were exposed to bright white light for seven hours. TUNEL labeling was used to detect photoreceptor apoptosis. At several intervals after the light injury, retinal ceruloplasmin was studied by quantitative PCR, immunohistochemistry, and western analysis. Expression of the secreted and expression of the membrane-anchored glycosyl phosphatidyl inositol (GPI) linked forms of ceruloplasmin were assesed in rat retina using primers specific for each form. Vitreous ceruloplasmin was detected by immunohistochemistry in Balb/c mouse eyes and by western analysis of aspirated vitreous from post-mortem human eyes.
   Results: Retinal ceruloplasmin mRNA was upregulated eight-fold following photic injury. Ceruloplasmin protein was detected throughout normal retinas by immunohistochemistry, with a specific increase in Muller cell labeling following photic injury. Western analysis confirmed an increase in ceruloplasmin protein following photic injury and revealed eight-fold more ceruloplasmin protein in normal retina than in brain. The mRNAs for both the secreted and GPI linked forms of ceruloplasmin were detected by RT-PCR in the retina. Ceruloplasmin protein was detected by western analysis of normal human vitreous and was increased in mouse vitreous following photic injury.
   Conclusions: Ceruloplasmin, a retinal ferroxidase, is upregulated at the mRNA and protein levels upon light damage. The increased protein is primarily in Muller cells. Ceruloplasmin is considerably more abundant in retina than in brain. The retina expresses both the GPI-linked and secreted forms of ceruloplasmin, and since vitreous ceruloplasmin increases following photic injury, some of the retinal ceruloplasmin may be secreted into the vitreous. Ceruloplasmin may protect the retina from oxidative stress by decreasing the amount of ferrous iron available to produce reactive oxygen species.
C1 Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Opthalmol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine
RP Dunaief, JL (通讯作者)，Stellar Chance Labs 305, 422 Curie Blvd, Philadelphia, PA 19104 USA.
OI Hahn, Paul/0000-0002-6574-388X
FU NEI NIH HHS [EY00417] Funding Source: Medline
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NR 43
TC 71
Z9 75
U1 0
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD APR 30
PY 2003
VL 9
IS 22-24
BP 151
EP 158
PG 8
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 676FG
UT WOS:000182740200001
PM 12724641
DA 2022-11-30
ER

PT J
AU Gange, WS
   Qiao, JMB
   Park, PJ
   McDonnell, JF
   Tan, ZQ
   Perlman, JI
   Bu, P
AF Gange, William S.
   Qiao, James B.
   Park, Paul J.
   McDonnell, James F.
   Tan, Zhiqun
   Perlman, Jay I.
   Bu, Ping
TI Protection of Retinal Function by Nucleoside Reverse Transcriptase
   Inhibitors Following Retinal Ischemia/Reperfusion Injury
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE retinal ischemia; nucleoside reverse transcriptase inhibitors;
   zidovudine; ischemia; reperfusion injury; electroretinogram; apoptosis;
   caspase-1
ID NLRP3 INFLAMMASOME; ISCHEMIA-REPERFUSION; ACTIVATION; DIDANOSINE
AB Purpose: Retinal ischemia/reperfusion (I/R) injury is a common cause of visual impairment and blindness for which there remain limited treatment options. Nucleoside reverse transcriptase inhibitors (NRTIs), such as zidovudine (AZT), have been shown to block the NLRP3 inflammasome and prevent retinal degeneration in a mouse model of age-related macular degeneration. The NLRP3 inflammasome has also been shown to be triggered in I/R injury. Therefore, we studied the neuroprotective effects of AZT using a pressure-induced retinal ischemia mouse model. Methods: C57BL/6J mice were randomly assigned to 1 of 2 treatment groups: vehicle-treated retinal I/R injury (n = 6) or AZT-treated retinal I/R injury (n = 6). Vehicle (1% dimethyl sulfoxide [DMSO] in phosphate-buffered saline [PBS]) or AZT 50 mg/kg in 1% DMSO in PBS were injected intraperitoneally twice daily for 5 days. On day 2 of treatment, retinal ischemia was induced by transient elevation of intraocular pressure for 45 min. Scotopic electroretinography (ERG) was used to quantify retinal function before and 1 week after retinal ischemic insult. Retinal morphology was examined 1 week after ischemic insult. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays and caspase 1 immunostaining was performed 24 h after retinal I/R injury. Results: Following I/R injury, ERG a- and b-wave amplitudes were significantly reduced in the vehicle-treated mice. AZT treatment significantly attenuated I/R-induced loss of retinal function as compared with vehicle-treated mice. Additionally, AZT-treated mice experienced significantly less inner retinal thinning as compared with vehicle-treated mice. TUNEL-positive cells were prevalent in the vehicle-treated I/R injury mouse retinas compared with the AZT-treated I/R injury mouse retinas. More caspase-1 immunoreactivity was detected in ganglion cell layer and inner nuclear layer (INL) in vehicle-treated I/R injury group than in AZT-treated I/R injury group. Conclusion: AZT treatment resulted in relative preservation of retinal structure and function following ischemic insult as compared with controls. This suggests AZT may have therapeutic value in the management of retinal ischemic diseases.
C1 [Gange, William S.; Qiao, James B.] Loyola Univ Chicago, Stritch Sch Med, Hlth Sci Div, 2160 S First Ave, Maywood, IL 60153 USA.
   [Park, Paul J.; McDonnell, James F.; Perlman, Jay I.; Bu, Ping] Loyola Univ Chicago, Stritch Sch Med, Hlth Sci Div, Dept Ophthalmol, Maywood, IL USA.
   [Tan, Zhiqun] Univ Calif Irvine, Inst Neurol Impairments & Neurol Disorders, Irvine, CA USA.
   [Perlman, Jay I.] Edward Hines Jr VA Hosp, Surg Serv, Hines, IL USA.
   [Bu, Ping] Edward Hines Jr VA Hosp, Res Serv, Hines, IL USA.
C3 Loyola University Chicago; Loyola University Chicago; University of
   California System; University of California Irvine; US Department of
   Veterans Affairs; Veterans Health Administration (VHA); Edward Hines Jr.
   VA Hospital; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); Edward Hines Jr. VA Hospital
RP Bu, P (通讯作者)，Loyola Univ Chicago, Stritch Sch Med, Hlth Sci Div, 2160 S First Ave, Maywood, IL 60153 USA.
EM pbu@luc.edu
OI Gange, William/0000-0002-6632-250X; , Ping/0000-0003-3526-1326
FU Richard A. Perritt Charitable Foundation; Illinois Society for the
   Prevention of Blindness
FX This work was supported by the Richard A. Perritt Charitable Foundation
   and Illinois Society for the Prevention of Blindness.
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NR 33
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD OCT 1
PY 2021
VL 37
IS 8
BP 485
EP 491
DI 10.1089/jop.2020.0083
EA AUG 2021
PG 7
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA XC0LB
UT WOS:000689740300001
PM 34448620
DA 2022-11-30
ER

PT J
AU Mukwaya, A
   Jensen, L
   Lagali, N
AF Mukwaya, Anthony
   Jensen, Lasse
   Lagali, Neil
TI Relapse of pathological angiogenesis: functional role of the basement
   membrane and potential treatment strategies
SO EXPERIMENTAL AND MOLECULAR MEDICINE
LA English
DT Review
AB Blinding eye diseases such as corneal neovascularization, proliferative diabetic retinopathy, and age-related macular degeneration are driven by pathological angiogenesis. In cancer, angiogenesis is key for tumor growth and metastasis. Current antiangiogenic treatments applied clinically interfere with the VEGF signaling pathway-the main angiogenic pathway-to inhibit angiogenesis. These treatments are, however, only partially effective in regressing new pathologic vessels, and the disease relapses following cessation of treatment. Moreover, the relapse of pathological angiogenesis can be rapid, aggressive and more difficult to treat than angiogenesis in the initial phase. The manner in which relapse occurs is poorly understood; however, recent studies have begun to shed light on the mechanisms underlying the revascularization process. Hypotheses have been generated to explain the rapid angiogenic relapse and increased resistance of relapsed disease to treatment. In this context, the present review summarizes knowledge of the various mechanisms of disease relapse gained from different experimental models of pathological angiogenesis. In addition, the basement membrane-a remnant of regressed vessels-is examined in detail to discuss its potential role in disease relapse. Finally, approaches for gaining a better understanding of the relapse process are discussed, including prospects for the management of relapse in the context of disease.
   Blood vessel formation: understanding relapse after inhibitory treatment Studying the sites of previous blood vessel occupation may explain how pathological vessel growth recurs after inhibitory treatment. Angiogenesis, the growth of new blood vessels, drives progression of cancerous tumors and blinding eye diseases. Existing treatments inhibiting critical growth factors are effective in the short term, but are often followed by aggressive relapse. Mukwaya et al., from Linkoping University in Sweden review the role of empty basement membrane sleeves (EBMS), the remnants of regressed blood vessels. Basement membrane supports endothelial cells, and EBMS could act as a scaffold for endothelial cells to rapidly rebuild blood vessels after anti-angiogenic treatment. Alternatively, EBMS may represent irreversibly abandoned conduits permanently isolated from the circulation, putatively through the deposition of excess collagen. Future work should carefully examine the role of basement membrane in the relapse of pathologic vessel growth.
C1 [Mukwaya, Anthony; Lagali, Neil] Linkoping Univ, Div Ophthalmol, Dept Biomed & Clin Sci, Fac Med, Linkoping, Sweden.
   [Jensen, Lasse] Linkoping Univ, Div Cardiovasc Med, Dept Hlth Med & Caring Sci, Fac Med, Linkoping, Sweden.
   [Lagali, Neil] Sorlandet Hosp Arendal, Dept Ophthalmol, Arendal, Norway.
C3 Linkoping University; Linkoping University
RP Mukwaya, A (通讯作者)，Linkoping Univ, Div Ophthalmol, Dept Biomed & Clin Sci, Fac Med, Linkoping, Sweden.
EM anthony.mukwaya@liu.se
RI Mukwaya, Anthony/K-2335-2019
OI Mukwaya, Anthony/0000-0002-9645-8942; Lagali, Neil/0000-0003-1079-4361
FU Ogonfonden, from the charity Synskadades Val; Swedish society of
   ophthalmology; Linkoping University
FX This work was supported by scholarships from Ogonfonden, from the
   charity Synskadades Val, and from the Swedish society of ophthalmology.
   Open Access funding provided by Linkoping University.
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NR 133
TC 9
Z9 9
U1 2
U2 4
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 1226-3613
EI 2092-6413
J9 EXP MOL MED
JI Exp. Mol. Med.
PD FEB
PY 2021
VL 53
IS 2
BP 189
EP 201
DI 10.1038/s12276-021-00566-2
EA FEB 2021
PG 13
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA QR4FN
UT WOS:000618142200001
PM 33589713
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Pellegrini, M
   Acquistapace, A
   Oldani, M
   Cereda, MG
   Giani, A
   Cozzi, M
   Staurenghi, G
AF Pellegrini, Marco
   Acquistapace, Alessandra
   Oldani, Marta
   Cereda, Matteo Giuseppe
   Giani, Andrea
   Cozzi, Mariano
   Staurenghi, Giovanni
TI Dark Atrophy: An Optical Coherence Tomography Angiography Study
SO OPHTHALMOLOGY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; INDOCYANINE GREEN ANGIOGRAPHY; VIVO FUNDUS
   AUTOFLUORESCENCE; MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; CHOROIDAL
   NEOVASCULARIZATION; FLUORESCEIN ANGIOGRAPHY; FLAVIMACULATUS;
   CHORIOCAPILLARIS; RPE
AB Purpose: To assess the status of choriocapillaris in eyes with macular atrophy secondary to age-related macular degeneration (AMD) (geographic atrophy [GA]) and Stargardt disease (STGD) using optical coherence tomography angiography (OCTA).
   Design: Prospective, observational case series.
   Participants: A total of 14 patients (20 eyes) affected by GA and 10 patients (20 eyes) affected by STGD.
   Methods: Each patient underwent a complete ophthalmological examination including fundus auto-fluorescence (FAF), dynamic simultaneous fluorescein angiography (FA) and indocyanine green angiography (ICGA), enhanced-depth imaging optical coherence tomography (EDI-OCT) (HRA+OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany), and OCTA using AngioVue technologies (Optovue Inc, Freemont, CA).
   Main Outcome Measures: An evaluation of the status of choriocapillaris in the 2 groups was performed.
   Results: Patients' mean age was 75 years for subjects with GA (median, 76 years; range, 63-88 years) and 61 years for STGD (median, 62 years; range, 40-74 years). Atrophy was bilateral in 42% (n = 6) of subjects with GA and 100% (n = 10) of subjects with STGD. In the early frames, FA displayed hyperfluorescence in the atrophic area in 100% (n = 20) of eyes affected by GA and 20% (n = 4) of eyes affected by STGD; dark choroid was present in 0% of GA eyes and 65% of STGD eyes (n = 13). Atrophy in ICGA late frames was hypofluorescent in 20% (n = 4) of GA eyes and 100% (n = 20) of STGD eyes. A ring at atrophy margins was detected in both FA (90%, n = 18) and ICGA (100%, n = 20) in STGD eyes. Mean subfoveal choroidal thickness was 156 mm (147, 42-362 mm) for GA eyes and 168 mm (167, 55-320 mm) for STGD eyes (P = 0.59). At OCTA evaluation, GA eyes showed persisting, rarefied choriocapillaris in correspondence of retinal pigment epithelium (RPE) atrophy in 80% (n = 16) of cases, whereas eyes affected by STGD had disappearance of this tissue in 100% (n = 20; P < 0.0001).
   Conclusions: Analysis of macular atrophy by OCTA in patients with STGD revealed an extensive loss of choriocapillaris in the central area with persisting tissue at its margins, whereas in those with GA the area of RPE loss showed persistent but rarefied choriocapillaris. (C) 2016 by the American Academy of Ophthalmology.
C1 [Pellegrini, Marco; Acquistapace, Alessandra; Oldani, Marta; Cereda, Matteo Giuseppe; Giani, Andrea; Cozzi, Mariano; Staurenghi, Giovanni] Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Eye Clin, 4th Floor,Bldg 51, Milan, Italy.
C3 University of Milan; Luigi Sacco Hospital
RP Staurenghi, G (通讯作者)，Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Eye Clin, 4th Floor,Bldg 51, Milan, Italy.
EM giovanni.staurenghi@unimi.it
RI ; Giani, Andrea/L-5926-2017; Staurenghi, Giovanni/K-4388-2017
OI pellegrini, marco/0000-0002-3550-591X; Cozzi,
   Mariano/0000-0001-7777-2461; Giani, Andrea/0000-0003-0682-1945;
   Staurenghi, Giovanni/0000-0002-2299-5251
FU Heidelberg Engineering; Optovue Inc; Zeiss Meditec; Nidek
FX The author(s) have made the following disclosure(s): M.C.: Grants and
   personal fees - Heidelberg Engineering.; G.S.: Grants and personal fees
   - Optovue Inc, Heidelberg Engineering, Zeiss Meditec, and Nidek.
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NR 39
TC 49
Z9 52
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD SEP
PY 2016
VL 123
IS 9
BP 1879
EP 1886
DI 10.1016/j.ophtha.2016.05.041
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EE3QE
UT WOS:000389508500017
PM 27448830
DA 2022-11-30
ER

PT J
AU Pons, M
   Marin-Castano, ME
AF Pons, Marianne
   Marin-Castano, Maria E.
TI Nicotine Increases the VEGF/PEDF Ratio in Retinal Pigment Epithelium: A
   Possible Mechanism for CNV in Passive Smokers with AMD
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; AGE-RELATED MACULOPATHY; SMOOTH-MUSCLE-CELLS;
   EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; ENVIRONMENTAL TOBACCO-SMOKE;
   ACTIVATED PROTEIN-KINASE; NONLETHAL OXIDANT INJURY; SUB-RPE DEPOSITS;
   BEAVER DAM EYE; MACULAR DEGENERATION
AB PURPOSE. Cigarette smoking is the strongest environmental risk factor for wet age-related macular degeneration (AMD). Inappropriate expression of proangiogenic vascular endothelial growth factor (VEGF) and antiangiogenic pigment epithelium derived factor (PEDF) may cause choroidal neovascularization (CNV), a key event in wet AMD, resulting in vision loss. Nicotine (NT), a potent angiogenic agent abundant in second-hand smoke, may play a major role in the pathogenesis of wet AMD. The purpose of this study was to evaluate the expression of nicotinic acetylcholine receptors (nAchR) in retinal pigment epithelium (RPE) and determine the effects of NT on RPE-derived VEGF and PEDF expression in the context of passive smoking.
   METHODS. Human RPE cells were treated with NT (10(-8) M), with or without the nAchR-nonspecific antagonist hexamethonium (HXM) (10(-5) M) for 72 hours. RPE sheets were microdissected from rats exposed to NT in drinking water (100 mu g/mL), with or without HXM (40 mg/kg/d, intraperitoneally), for 72 hours. Cell death was determined by cell count and proliferation by Western blot for proliferating cell nuclear antigen (PCNA). nAchR expression was examined by real-time PCR and Western blot. ERK activation was evaluated by Western blot analysis. VEGF and PEDF expression was assessed by ELISA, Western blot, and real-time PCR.
   RESULTS. Cultured RPE cells constitutively expressed the nAchR alpha 3, alpha 10, and beta 1 subunits, with beta 1 being the most prevalent. The nAchR alpha 4, alpha 5, alpha 7, and beta 2 subunits were detected in RPE sheets from rats, among which alpha 4 is the predominant subtype. NT, which did not result in either cell death or proliferation, induced beta 1 nAchR, upregulated VEGF, and downregulated PEDF expression through nAChR in ARPE-19 cells. Transcriptional activation of the nAchR alpha 4 subunit and nAChR-mediated upregulation of VEGF and PEDF were observed in RPE from rats exposed to NT.
   CONCLUSIONS. NT increased the VEGF-to-PEDF ratio in the RPE through nAchR in vitro and in vivo. This alteration in the ratio may play a key role in the progression to wet AMD in passive smokers. (Invest Ophthalmol Vis Sci. 2011; 52: 3842-3853) DOI: 10.1167/iovs.10-6254
C1 [Pons, Marianne; Marin-Castano, Maria E.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA.
C3 Bascom Palmer Eye Institute; University of Miami
RP Marin-Castano, ME (通讯作者)，Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, 1638 NW 10th Ave, Miami, FL 33136 USA.
EM mcastano@med.miami.edu
RI Datta, Sayantan/D-1369-2010
FU Flight Attendant Medical Research Institute [072100_CIA]; Research to
   Prevent Blindness; National Institutes of Health [P30-EY14801]; NATIONAL
   EYE INSTITUTE [P30EY014801] Funding Source: NIH RePORTER
FX Supported by Flight Attendant Medical Research Institute Grant
   072100_CIA; an unrestricted grant from Research to Prevent Blindness to
   the University of Miami; and National Institutes of Health Grant
   P30-EY14801.
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NR 86
TC 59
Z9 64
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2011
VL 52
IS 6
BP 3842
EP 3853
DI 10.1167/iovs.10-6254
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800CF
UT WOS:000293335400055
PM 21330654
OA Green Published
DA 2022-11-30
ER

PT J
AU Primo, SA
AF Primo, Susan A.
TI Implantable miniature telescope: Lessons learned
SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION
LA English
DT Review
DE Implantable miniature telescope; Visual prosthesis; Age-related macular
   degeneration; Visual impairment; Vision rehabilitation
ID VISUAL-FUNCTION-QUESTIONNAIRE; DAILY VISION SCALE; MACULAR DEGENERATION;
   EYE; OUTCOMES; SAFETY; ACUITY; IMPACT
AB BACKGROUND: The Implantable Miniature Telescope (IMT (TM)) is a telescopic prosthesis that, combined with the optics of the cornea, constitutes an intraocular magnifying system. It is indicated for use in patients with stable, nonfoveal sparing, bilateral, stable, age-related macular degeneration (end-stage) with associated scotomas. The telescope prosthesis is implanted in only one of the patient's eyes. In this way, the implanted eye provides improved visual acuity, and the nonimplanted eye continues to provide peripheral vision for ambulation. Two hundred seventeen patients with end-stage AMD were enrolled in a prospective, multicenter, open-label trial (IMT-002) beginning in 2003. The implanted eye was the worse eye for most patients based on a selection rule set by the U.S. Food and Drug Administration (FDA) protocol; however, in most cases (90%), visual acuity improvement goals were met with the device. This report will retrospectively look at 2 selected patients implanted at the Emory Eye Center in Atlanta as part of that trial to derive lessons for subject and eye selection criteria.
   CASE REPORTS: Two cases were selected to represent patients' levels of functional success and satisfaction. Determination of their visual and functional outcome at 1-year postimplantation was based on best-corrected visual acuity and the National Eye Institute Visual Functioning Questionnaire 25-Item quality-of-life survey. Four years after implantation, 1 patient continued to use the telescope prosthesis eye for all visual activities; the other patient did not perceive any benefit from the device and continued to primarily use the fellow nonimplanted eye. The benefit of the telescopic prosthesis was most likely accounted for by the level of visual acuity in. both eyes postimplantation and eye dominance.
   CONCLUSION: Proper eye selection chosen for implantation with the telescope prosthesis appears to be an important if not critical factor in determining patient satisfaction for visual processing and functional success. Based on the author's experience with the IMT, optometrists can aid the multidisciplinary team by preoperatively determining which eye, if implanted,. offers the optimal potential functional benefit for appropriate candidates. Optometry 2010;81:86-93
C1 [Primo, Susan A.] Emory Eye Ctr, Atlanta, GA USA.
RP Primo, SA (通讯作者)，Emory Univ, Sch Med, Dept Ophthalmol, 1365B Clifton Rd NE, Atlanta, GA 30322 USA.
EM sprimo@emory.edu
FU VisionCare Ophthalmic Technologies, Inc.; NIH NEI [EY06360]; Research to
   Prevent Blindness, Inc.
FX Susan A. Primo has no commercial or financial interests associated with
   the device. The long-term follow-up study was supported by a clinical
   research trial sponsored by VisionCare Ophthalmic Technologies, Inc.;
   This research paper was supported in part by NIH NEI Grant EY06360 and
   an unrestricted grant from Research to Prevent Blindness, Inc.
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U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1529-1839
J9 OPTOMETRY
JI Optometry
PD FEB
PY 2010
VL 81
IS 2
BP 86
EP 93
DI 10.1016/j.optm.2009.08.014
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800MA
UT WOS:000293363800007
PM 20152782
DA 2022-11-30
ER

PT J
AU Goverdhan, SV
   Hannan, S
   Newsom, RB
   Luff, AJ
   Griffiths, H
   Lotery, AJ
AF Goverdhan, S. V.
   Hannan, S.
   Newsom, R. B.
   Luff, A. J.
   Griffiths, H.
   Lotery, A. J.
TI An analysis of the CFHY402H genotype in AMD patients and controls from
   the UK, and response to PDT treatment
SO EYE
LA English
DT Article
DE CFH; AMD; CNV; photodynamic; acuity; association
ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; Y402H
   VARIANT; RISK; INFLAMMATION; POLYMORPHISM; ATROPHY; GENE
AB Aim Mutation in the complement factor H (CFH) gene is an important risk factor for age-related macular degeneration (AMD). In this study, we identified the strength of the CFH Y402H gene variant association in a UK AMD cohort and tested the hypothesis that this variant may influence the biological response of choroidal neovascularisation (CNV) following photodynamic therapy (PDT) for CNV.
   Methods A total of 557 cases with AMD and 551 normal controls were genotyped for the CFH Y402H (1277 C/T) variant using the 50 nuclease TaqMan assay for allelic discrimination. The CFH gene association for AMD, for the different CNV subtypes and for patients needing PDT was estimated. Twenty-seven PDT-treated patients were followed up for 15 months with ETDRS-derived vision, clinical examination, and fundus angiography. Individuals with different CFH genotypes were then analysed for any association with visual change following PDT.
   Results The risk association for AMD with the CFH CC genotype ( odd ratio (OR) 3.62, P(c)< 0.0001) was similar to that reported in other Caucasian cohorts. The magnitude and strength of this association was stronger in AREDS stages 2-4 (ORs = 4.48, 2.69, and 5.17). ORs for the risk of predominantly classic CNV were significantly raised for both the CC (OR 17.87, P < 0.0001) and CT (OR = 9.06, P = 0.0002) genotypes. The number of patients carrying the high-risk C allele was 70.4% in those requiring PDT as compared to 52.3% in the non-PDT group (OR = 2.16, P = 0.011), and presence of the CC genotype significantly increased the risk of PDT (OR = 5.48, P = 0.015). The degree of visual loss following PDT was significantly higher in the CFH CC genotype group (P = 0.038); 50% of CC cases (n = 13) and 45% of the CTcases (n = 12) lost 15 or more ETDRS letters at final follow-up.
   Conclusion In this UK cohort of AMD patients, the CFH Y402H variant was significantly enriched in patients with predominantly classic CNV. Patients homozygous for the CFH Y402H genotype seem to have worse visual acuity after PDT.
C1 [Goverdhan, S. V.; Griffiths, H.; Lotery, A. J.] Univ Southampton, Southampton Gen Hosp, Clin Neurosci Div, Southampton SO16 6YD, Hants, England.
   [Goverdhan, S. V.; Hannan, S.; Newsom, R. B.; Luff, A. J.; Lotery, A. J.] Univ Southampton, Southampton Gen Hosp, Southampton Eye Unit, Southampton SO16 6YD, Hants, England.
C3 University of Southampton; University of Southampton
RP Lotery, AJ (通讯作者)，Univ Southampton, Southampton Gen Hosp, Clin Neurosci Div, Mailpoint 806,Tremona Rd, Southampton SO16 6YD, Hants, England.
EM a.j.lotery@soton.ac.uk
OI newsom, Richard/0000-0002-2221-0653; Lotery, Andrew/0000-0001-5541-4305
FU Wellcome Trust [076169] Funding Source: Medline
CR Alexander JJ, 2005, J AM SOC NEPHROL, V16, P52, DOI 10.1681/ASN.2004090778
   Anand R, 2000, OPHTHALMOLOGY, V107, P2224
   Baird PN, 2006, INVEST OPHTH VIS SCI, V47, P4194, DOI 10.1167/iovs.05-1285
   DERODRIGUEZ CS, 2004, MOL IMMUNOL, V41, P355
   Donoso LA, 2006, SURV OPHTHALMOL, V51, P137, DOI 10.1016/j.survophthal.2005.12.001
   Edwards AO, 2005, SCIENCE, V308, P421, DOI 10.1126/science.1110189
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   Haines JL, 2005, SCIENCE, V308, P419, DOI 10.1126/science.1110359
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NR 14
TC 62
Z9 66
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD JUN
PY 2008
VL 22
IS 6
BP 849
EP 854
DI 10.1038/sj.eye.6702830
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 312HL
UT WOS:000256659800019
PM 17464302
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Johnson, TM
   Glaser, BM
AF Johnson, T. Mark
   Glaser, Bert M.
TI Focal laser ablation of retinal angiomatous proliferation
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; retinal angiomatous proliferation;
   laser photocoagulation; indocyanine green angiography
ID MACULAR DEGENERATION; CHOROIDAL ANASTOMOSES; DETACHMENTS
AB Purpose: To evaluate the feasibility of focal laser ablation of retinal angiornatous proliferation (RAP) identified with clinical examination and high-speed indocyanine green (ICG) imaging in patients with age-related macular degeneration.
   Methods: In this retrospective, interventional case series, 16 consecutive eyes of 15 patients with macular degeneration and leakage from a stage I or II RAP lesion were identified. RAP lesions were identified using clinical examination and high-speed ICG imaging. High-speed ICG imaging was used to identify the intraretinal component of the lesion. RAP lesions were treated with a 100- to 200-mu m green or yellow wavelength laser spot that was applied to completely ablate the intraretinal component of the lesion. In eyes with stage II lesions, the subretinal component of the lesion was not treated. Early Treatment of Diabetic Retinopathy Study visual acuity, optical coherence tomography retinal thickness, angiographic leakage, and progression of the angiornatous process shown by ICG imaging were evaluated preoperatively and postoperatively.
   Results: Sixteen eyes underwent successful ablation of the RAP lesions with an average of 1.9 treatment sessions. At a mean follow-up of 15.5 months, 94% of eyes had stable or improved visual acuity. Only 6% of eyes had a loss of 3 lines of visual acuity. The average visual acuity at the last follow-up was 20/45 in the stage I lesion group and 20/160 in the stage II lesion group. Of the patients, 87.5% had a reduction in retinal edema and subretinal fluid, with 69% of patients having complete resolution of retinal edema and subretinal fluid; 14% of patients had progression to retinal choroidal anastomoses. No treatment complications were encountered.
   Conclusion: Focal laser photocoagulation of RAP lesions appears to be feasible. This treatment appears to be a safe method of managing the leakage from RAP. Treatment of solely the intraretinal component of the lesion may be adequate to control leakage. Treatment may allow the angiornatous process to be arrested, resulting in stabilization of visual acuity. Visual acuity results appear to be better for patients with early stage lesions.
C1 Natl Retina Inst, Chevy Chase, MD 20815 USA.
RP Johnson, TM (通讯作者)，Natl Retina Inst, Suite 101,5530 Wisconsin Ave, Chevy Chase, MD 20815 USA.
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NR 11
TC 33
Z9 37
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD SEP
PY 2006
VL 26
IS 7
BP 765
EP 772
DI 10.1097/01.iae.0000244264.98642.af
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 180TQ
UT WOS:000247389300009
PM 16963849
DA 2022-11-30
ER

PT J
AU Klevering, BJ
   Maugeri, A
   Wagner, A
   Go, SL
   Vink, C
   Cremers, FPM
   Hoyng, CB
AF Klevering, BJ
   Maugeri, A
   Wagner, A
   Go, SL
   Vink, C
   Cremers, FPM
   Hoyng, CB
TI Three families displaying the combination of Stargardt's disease with
   cone-rod dystrophy or retinitis pigmentosa
SO OPHTHALMOLOGY
LA English
DT Article
ID TRANSPORTER GENE ABCR; MACULAR DEGENERATION; JAPANESE PATIENTS;
   MUTATIONS; AGE; PHOTORECEPTORS; CLASSIFICATION; EXPRESSION; PHENOTYPE;
   SYSTEM
AB Objective: To investigate the clinical spectrum and molecular causes of retinal dystrophies in 3 families.
   Design: Family molecular genetics study.
   Participants: Sixteen patients and 15 relatives in 3 families.
   Methods: Members of 3 families with multiple ABCA4-associated retinal disorders were clinically evaluated. Deoxyribonucleic acid samples of all affected individuals and their family members were analyzed for variants in all 50 exons of the ABCA4 gene.
   Main Outcome Measures: ABCA4-associated retinal phenotypes and mutations in the ABCA4 gene.
   Results: In family A, 2 sisters were diagnosed with Stargardt's disease (STGD); the eldest sister was compound heterozygous for the mild 2588G-->C and the severe 768G-->T mutation. Another patient in this family with a severe type of retinitis pigmentosa (RP) carried the 768G-->T mutation homozygously. In family B, 2 siblings presented with an RP of severity similar to that encountered in family A. Both were homozygous for the severe IVS33+1G-->A mutation. Two other family members with STGD were compound heterozygous for the 2588G-->C and IVS33+1G-->A mutations. In family C, all 5 siblings of generation 11 demonstrated age-related macular degeneration (AMD). In generations III and IV, 2 STGD patients and 1 cone-rod dystrophy (CRD) patient were present. In 1 STGD patient we identified a heterozygous 768G-->T mutation. Sequence analysis of the entire ABCA4 gene did not reveal the remaining 2 mutations. Nevertheless, the 2 patients with STGD, the patient with CRD, and 2 of the AMD patients shared a common haplotype spanning the ABCA4 gene.
   Conclusions: Different mutations in the ABCA4 gene are the cause of STGD and RP or CRD in at least 2 and, possibly, 3 families. Patients with RP caused by ABCA4 mutations are characterized by an early onset and rapid progression of their retinal dystrophy, with extensive chorioretinal atrophy resulting in a very low visual acuity. Various combinations of relatively rare retinal disorders such as STGD, CRD, and RP in one family may not be as uncommon as once believed, in view of the relatively high carrier frequency of ABCA4 mutations (about 5%) in the general population. (C) 2004 by the American Academy of Ophthalmology.
C1 Univ Nijmegen, Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands.
   Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.
   Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands.
C3 Radboud University Nijmegen; Radboud University Nijmegen; Erasmus
   University Rotterdam
RP Klevering, BJ (通讯作者)，Univ Nijmegen, Med Ctr, Dept Ophthalmol, POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM B.Klevering@ohk.umcn.nl
RI Hoyng, C.B./H-8050-2014; Cremers, Frans/A-5625-2014; Klevering,
   B.J./L-4434-2015
OI Cremers, Frans/0000-0002-4954-5592; 
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NR 42
TC 35
Z9 42
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAR
PY 2004
VL 111
IS 3
BP 546
EP 553
DI 10.1016/j.ophtha.2003.06.010
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 780BR
UT WOS:000189351800023
PM 15019334
DA 2022-11-30
ER

PT J
AU Almasi, R
   Vafaei, A
   Kazeminasab, E
   Rabbani, H
AF Almasi, Ramin
   Vafaei, Abbas
   Kazeminasab, Elahe
   Rabbani, Hossein
TI Automatic detection of microaneurysms in optical coherence tomography
   images of retina using convolutional neural networks and transfer
   learning
SO SCIENTIFIC REPORTS
LA English
DT Article
ID FLUORESCEIN ANGIOGRAPHY; DIABETIC-RETINOPATHY
AB Microaneurysms (MAs) are pathognomonic signs that help clinicians to detect diabetic retinopathy (DR) in the early stages. Automatic detection of MA in retinal images is an active area of research due to its application in screening processes for DR which is one of the main reasons of blindness amongst the working-age population. The focus of these works is on the automatic detection of MAs in en face retinal images like fundus color and Fluorescein Angiography (FA). On the other hand, detection of MAs from Optical Coherence Tomography (OCT) images has 2 main advantages: first, OCT is a non-invasive imaging technique that does not require injection, therefore is safer. Secondly, because of the proven application of OCT in detection of Age-Related Macular Degeneration, Diabetic Macular Edema, and normal cases, thanks to detecting MAs in OCT, extensive information is obtained by using this imaging technique. In this research, the concentration is on the diagnosis of MAs using deep learning in the OCT images which represent in-depth structure of retinal layers. To this end, OCT B-scans should be divided into strips and MA patterns should be searched in the resulted strips. Since we need a dataset comprising OCT image strips with suitable labels and such large labelled datasets are not yet available, we have created it. For this purpose, an exact registration method is utilized to align OCT images with FA photographs. Then, with the help of corresponding FA images, OCT image strips are created from OCT B-scans in four labels, namely MA, normal, abnormal, and vessel. Once the dataset of image strips is prepared, a stacked generalization (stacking) ensemble of four fine-tuned, pre-trained convolutional neural networks is trained to classify the strips of OCT images into the mentioned classes. FA images are used once to create OCT strips for training process and they are no longer needed for subsequent steps. Once the stacking ensemble model is obtained, it will be used to classify the OCT strips in the test process. The results demonstrate that the proposed framework classifies overall OCT image strips and OCT strips containing MAs with accuracy scores of 0.982 and 0.987, respectively.
C1 [Almasi, Ramin; Vafaei, Abbas; Kazeminasab, Elahe] Univ Isfahan, Fac Engn, Dept Comp Engn, Esfahan, Iran.
   [Rabbani, Hossein] Isfahan Univ Med Sci, Med Image & Signal Proc Res Ctr, Esfahan, Iran.
C3 University of Isfahan; Isfahan University Medical Science
RP Vafaei, A (通讯作者)，Univ Isfahan, Fac Engn, Dept Comp Engn, Esfahan, Iran.; Rabbani, H (通讯作者)，Isfahan Univ Med Sci, Med Image & Signal Proc Res Ctr, Esfahan, Iran.
EM abbas_vafaei@eng.ui.ac.ir; rabbani.h@ieee.org
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NR 39
TC 1
Z9 1
U1 1
U2 1
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD AUG 17
PY 2022
VL 12
IS 1
AR 13975
DI 10.1038/s41598-022-18206-8
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 3W1XA
UT WOS:000842145300003
PM 35978087
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Bhattacharya, S
   Yin, JG
   Huo, WH
   Chaum, E
AF Bhattacharya, Sujoy
   Yin, Jinggang
   Huo, Weihong
   Chaum, Edward
TI Modeling of mitochondrial bioenergetics and autophagy impairment in
   MELAS-mutant iPSC-derived retinal pigment epithelial cells
SO STEM CELL RESEARCH & THERAPY
LA English
DT Article
DE Age-related macular degeneration; MELAS; iPSC-derived retinal pigment
   epithelium; Autophagy flux; Mitophagy; Mitochondrial heteroplasmy;
   Prom1/CD133; AMPK alpha; PGC-1 alpha; Regenerative medicine
ID DNA DAMAGE; STAT3; PARKIN; HETEROPLASMY; DYSFUNCTION; OXIDATION;
   DEPLETION; DEFECTS; PINK1; MTDNA
AB Background: Mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage in the retinal pigment epithelium (RPE) have been implicated in the pathogenesis of age-related macular degeneration (AMD). However, a deeper understanding is required to determine the contribution of mitochondrial dysfunction and impaired mitochondrial autophagy (mitophagy) to RPE damage and AMD pathobiology. In this study, we model the impact of a prototypical systemic mitochondrial defect, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), in RPE health and homeostasis as an in vitro model for impaired mitochondrial bioenergetics.
   Methods: We used induced pluripotent stem cells (iPSCs) derived from skin biopsies of MELAS patients (m.3243A>G tRNA leu mutation) with different levels of mtDNA heteroplasmy and differentiated them into RPE cells. Mitochondrial depletion of ARPE-19 cells (p(0) cells) was also performed using 50 ng/mL ethidium bromide (EtBr) and 50 mg/ml uridine. Cell fusion of the human platelets with the p(0) cells performed using polyethylene glycol (PEG)/suspension essential medium (SMEM) mixture to generate platelet/RPE "cybrids."Confocal microscopy, FLowSight Imaging cytometry, and Seahorse XF Mito Stress test were used to analyze mitochondrial function. Western Blotting was used to analyze expression of autophagy and mitophagy proteins.
   Results: We found that MELAS iPSC-derived RPE cells exhibited key characteristics of native RPE. We observed heteroplasmy-dependent impairment of mitochondrial bioenergetics and reliance on glycolysis for generating energy in the MELAS iPSC-derived RPE. The degree of heteroplasmy was directly associated with increased activation of signal transducer and activator of transcription 3 (STAT3), reduced adenosine monophosphate-activated protein kinase alpha (AMPK alpha) activation, and decreased autophagic activity. In addition, impaired autophagy was associated with aberrant lysosomal function, and failure of mitochondrial recycling. The mitochondria-depleted p(0) cells replicated the effects on autophagy impairment and aberrant STAT3/AMPK alpha signaling and showed reduced mitochondrial respiration, demonstrating phenotypic similarities between p(0) and MELAS iPSC-derived RPE cells.
   Conclusions: Our studies demonstrate that the MELAS iPSC-derived disease models are powerful tools for dissecting the molecular mechanisms by which mitochondrial DNA alterations influence RPE function in aging and macular degeneration, and for testing novel therapeutics in patients harboring the MELAS genotype.
C1 [Bhattacharya, Sujoy; Yin, Jinggang; Huo, Weihong; Chaum, Edward] Vanderbilt Univ Sch Med, Dept Ophthalmol & Visual Sci, 2311 Pierce Ave, Nashville, TN 37232 USA.
C3 Vanderbilt University
RP Chaum, E (通讯作者)，Vanderbilt Univ Sch Med, Dept Ophthalmol & Visual Sci, 2311 Pierce Ave, Nashville, TN 37232 USA.
EM edward.chaum@vumc.org
OI Chaum, Edward/0000-0003-3542-8376; Bhattacharya,
   Sujoy/0000-0003-4443-9691
FU Shulsky Foundation research grant; Potocsnak Family Vision Research
   Center at the Vanderbilt Eye Institute; Margy Ann and J Donald M Gass
   Chair endowment; Vanderbilt Vision Research Center NEI Core Grant
   [P30-EY008126]; Research to Prevent Blindness, Inc (New York, NY)
FX This study was supported by a Shulsky Foundation research grant, the
   Potocsnak Family Vision Research Center at the Vanderbilt Eye Institute,
   the Margy Ann and J Donald M Gass Chair endowment, Vanderbilt Vision
   Research Center NEI Core Grant (P30-EY008126), and an unrestricted
   departmental research grant from Research to Prevent Blindness, Inc (New
   York, NY).
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NR 72
TC 0
Z9 0
U1 1
U2 1
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1757-6512
J9 STEM CELL RES THER
JI Stem Cell Res. Ther.
PD JUN 17
PY 2022
VL 13
IS 1
AR 260
DI 10.1186/s13287-022-02937-6
PG 21
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA 2E9IA
UT WOS:000812533000003
PM 35715869
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Xu, JX
   Liu, XL
   Zhang, XY
   Marshall, B
   Dong, Z
   Liu, YT
   Espinosa-Heidmann, DG
   Zhang, M
AF Xu, Jinxian
   Liu, Xinglou
   Zhang, Xinyang
   Marshall, Brendan
   Dong, Zheng
   Liu, Yutao
   Espinosa-Heidmann, Diego G.
   Zhang, Ming
TI Ocular cytomegalovirus latency exacerbates the development of choroidal
   neovascularization
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE cytomegalovirus; age-related macular degeneration; choroidal
   neovascularization; inflammation; VEGF
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; VEGF-A; PROMOTES
   ANGIOGENESIS; NLRP3 INFLAMMASOME; BLOOD-PRESSURE; ANIMAL-MODELS; AGE;
   INFECTION; REACTIVATION
AB Age-related macular degeneration (AMD) is a complex, multifactorial, progressive disease which represents a leading cause of irreversible visual impairment and blindness in older individuals. Human cytomegalovirus (HCMV), which infects 50-80% of humans, is usually acquired during early life and persists in a latent state for the life of the individual. In view of its previously described pro-angiogenic properties, we hypothesized that cytomegalovirus might be a novel risk factor for progression to an advanced form, neovascular AMD, which is characterized by choroidal neovascularization (CNV). The purpose of this study was to investigate if latent ocular murine cytomegalovirus (MCMV) infection exacerbated the development of CNV in vascular endothelial growth factor (VEGF)-overexpressing VEGF-A(hyper) mice. Here we show that neonatal infection with MCMV resulted in dissemination of virus to various organs throughout the body including the eye, where it localized principally to the choroid in both VEGF-overexpressingVEGF-A(hyper) and wild-type(WT) 129 mice. By 6 months post-infection, no replicating virus was detected in eyes and extraocular tissues, although virus DNA was still present in all eyes and extraocular tissues of both VEGF-A(hyper) and WT mice. Expression of MCMV immediate early (IE) 1 mRNA was detected only in latently infected eyes of VEGF-A(hyper) mice, but not in eyes of WT mice. Significantly increased CNV was observed in eyes of MCMV-infected VEGF-A(hyper) mice compared to eyes of uninfected VEGF-A(hyper) mice, while no CNV lesions were observed in eyes of either infected or uninfected WT mice. Protein levels of several inflammatory/angiogenic factors, particularly VEGF and IL-6, were significantly higher in eyes of MCMV-infected VEGF-A(hyper) mice, compared to uninfected controls. Initial studies of ocular tissue from human cadavers revealed that HCMV DNA was present in four choroid/retinal pigment epithelium samples from 24 cadavers. Taken together, our data suggest that ocular HCMV latency could be a significant risk factor for the development of AMD. (c) 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 [Xu, Jinxian; Liu, Xinglou; Zhang, Xinyang; Marshall, Brendan; Dong, Zheng; Liu, Yutao; Zhang, Ming] Augusta Univ, Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA.
   [Xu, Jinxian; Liu, Xinglou; Zhang, Xinyang; Liu, Yutao; Espinosa-Heidmann, Diego G.; Zhang, Ming] Augusta Univ, James & Jean Culver Vis Discovery Inst, Augusta, GA 30912 USA.
   [Liu, Xinglou] Huazhong Univ Sci & Technol, Tongli Hosp, Dept Pediat, Wuhan, Peoples R China.
   [Dong, Zheng] Charlie Norwood VA Med Ctr, Augusta, GA USA.
   [Liu, Yutao; Espinosa-Heidmann, Diego G.] Augusta Univ, Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA.
C3 University System of Georgia; Augusta University; University System of
   Georgia; Augusta University; Huazhong University of Science &
   Technology; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); University System of Georgia; Augusta University
RP Zhang, M (通讯作者)，Augusta Univ, Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA.
EM mzhang@augusta.edu
OI Zhang, Ming/0000-0002-4012-3932; Xu, Jinxian/0000-0001-9674-8029
FU NIH [EY026642]
FX This work was supported by NIH grant EY026642.
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   Zhang M, 2005, INVEST OPHTH VIS SCI, V46, P252, DOI 10.1167/iovs.04-0537
   ZHANG M, 2018, INVEST OPHTH VIS SCI, V59
NR 95
TC 6
Z9 6
U1 1
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3417
EI 1096-9896
J9 J PATHOL
JI J. Pathol.
PD JUN
PY 2020
VL 251
IS 2
BP 200
EP 212
DI 10.1002/path.5447
EA MAY 2020
PG 13
WC Oncology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Pathology
GA LU2DV
UT WOS:000535215800001
PM 32243583
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Xia, F
   Wu, LC
   Weng, CH
   Zhou, XT
AF Xia, Fei
   Wu, Liangcheng
   Weng, Chenghai
   Zhou, Xingtao
TI Causes and Three-year Incidence of Irreversible Visual Impairment in
   Jing-An District, Shanghai, China from 2010-2015
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Blindness; Low vision; Myopia macular degeneration; Diabetic retinopathy
ID GLOBAL BURDEN; ADULT-POPULATION; BLINDNESS; PREVALENCE
AB Background: The registry system can be used to observe the distribution trend of diseases and analyze the related data to provide useful information in a way that enables the government to take appropriate interventional measures. The purpose of this study was to determine the causes and three-year incidence of newly registered disabled patients who were blind or had low vision in Jing-An District, Shanghai, China from 2010 to 2015.
   Methods: Data from the registration system of visual disability in Jing-An District, Shanghai from 2010 to 2015 were collected and analyzed. In this registry, the only person with permanent visual impairment (VI) was identified as being a certified visually impaired person. The main causes of visual disability were obtained, the three-year incidence of visual disability was calculated, and the relationships between blindness or low vision and age, as well as those between blindness or low vision and gender, were analyzed.
   Results: Six-hundred and forty-six newly certified people with VI were registered, including 206 blind patients and 440 low vision patients. The major causes of blindness were myopia macular degeneration (MMD, 23.30%), glaucoma (20.39%), and age-related macular degeneration (AMD, 17.96%). The three leading causes of low vision were MMD (58.86%), AMD (16.36%), and diabetic retinopathy (DR, 7.27%). DR (16.0%) was the first leading cause of blindness and the second leading cause of VI in patients aged 30-59 yrs. from 2010 to 2015. The three-year incidences of blindness in 2010-2012 and 2013-2015(P = 0.43), which remained stable throughout this time period, were 32.74/100000 and 36.51/100000, respectively. However, the three-year incidence of low vision was 64.51/100000 in 2010-2012 and 83.58/100000 in 2013-2015(P = 0.007), which shows that the incidence increased significantly due to the increase of patients with low vision caused by MMD and DR (P = 0.003 and P = 0.01, respectively).
   Conclusions: MMD, glaucoma, and AMD were the main causes of blindness, while DR was becoming a major cause of VI, especially in working-age people of Jing-An District, Shanghai, China.
C1 [Xia, Fei; Wu, Liangcheng; Weng, Chenghai] Fudan Univ, Dept Ophthalmol, Jing An Dist Ctr,Shangai Med Coll, Hosp Shanghai,Huashan Hosp,Jing An Branch, Shanghai, Peoples R China.
   [Zhou, Xingtao] Fudan Univ, Dept Ophthalmol & Visual Sci, Eye & ENT Hosp, Shanghai Med Coll, Shanghai, Peoples R China.
C3 Fudan University; Fudan University
RP Wu, LC (通讯作者)，Fudan Univ, Dept Ophthalmol, Jing An Dist Ctr,Shangai Med Coll, Hosp Shanghai,Huashan Hosp,Jing An Branch, Shanghai, Peoples R China.
EM liangchengwudoc@126.com
RI zhou, xt/GWZ-9212-2022; zhou, xing/GQP-4516-2022
FU three-year action plan of a demonstrative project for improving the
   organization of the public health system [2015-82-20]; eye disease
   prevention personnel training plan of Shanghai, China
   [15GWZK0601-QJGG02]; Project of Shanghai Science and Technology
   [17411950200, 17411950208]
FX This study was supported by the three-year action plan of a
   demonstrative project for improving the organization of the public
   health system (NO: 2015-82-20), as well as by the eye disease prevention
   personnel training plan of Shanghai, China (15GWZK0601-QJGG02) and
   Project of Shanghai Science and Technology(No. 17411950200&
   17411950208).
CR Bener Abdulbari, 2012, Glob J Health Sci, V5, P134, DOI 10.5539/gjhs.v5n2p134
   Bourne R, 2013, OPHTHAL EPIDEMIOL, V20, P33, DOI 10.3109/09286586.2012.741279
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NR 22
TC 8
Z9 9
U1 0
U2 2
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD NOV 28
PY 2017
VL 17
AR 216
DI 10.1186/s12886-017-0603-3
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FO4IQ
UT WOS:000416806000001
PM 29179756
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Amore, FM
   Fasciani, R
   Silvestri, V
   Crossland, MD
   de Waure, C
   Cruciani, F
   Reibaldi, A
AF Amore, Filippo M.
   Fasciani, Romina
   Silvestri, Valeria
   Crossland, Michael D.
   de Waure, Chiara
   Cruciani, Filippo
   Reibaldi, Alfredo
TI Relationship between fixation stability measured with MP-1 and reading
   performance
SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS
LA English
DT Article
DE fixation; microperimeter; reading speed; visual impairment
ID SCANNING LASER OPHTHALMOSCOPE; MACULAR DISEASE; EYE-MOVEMENTS;
   RETINITIS-PIGMENTOSA; RETINAL LOCATION; PERCEPTUAL SPAN; VISION; SPEED;
   AGE; MICROPERIMETER
AB BackgroundPeople with visual impairment have reduced reading performance, which is thought to be related to unstable or eccentric fixation. New microperimeters such as the MP-1 offer straightforward analysis of fixation stability. The aim of this study was to investigate the relationship between fixation stability and reading speed in a large cohort of people with diverse causes of visual impairment and to verify the correlation between reading speed and different methods for the quantification of fixation.
   MethodsThe better eye of one hundred and twenty subjects was assessed. Fixation values were obtained from the MP-1 microperimeter. Reading speed was evaluated using newspaper text with magnifiers if required.
   ResultsThe poorest fixation stability and reading performance was found in people with age-related macular degeneration while the best fixation was in retinitis pigmentosa subjects. A linear relationship was found between reading speed and the proportion of fixations within 2 degrees (r(2)=0.51, p<0.001) and 4 degrees (r(2)=0.36, p<0.001). A negative correlation was found between reading speed and all three bivariate contour ellipse areas (BCEA; for log transformation of 1-S.D., 2-S.D. and 3-S.D.: r(2)=0.39, p<0.001). In a multiple regression model, proportion of points falling within 2 degrees and 4 degrees circle was significantly related to reading speed (r(2)=0.55, p<0.01; r(2)=0.43 p<0.01); also BCEAs values were strongly related to reading ability only in patients with central vision loss (r(2)=0.62, p<0.01 for LogBCEA 68.2%; r(2)=0.61, p<0.01 for LogBCEA 95.4% and 99.6%) and peripheral defect (r(2)=0.52, p<0.01 for LogBCEA 68.2%; r(2)=0.50, p<0.01 for LogBCEA 95.4%; r(2)=0.49, p<0.01 for LogBCEA 99.6%) but not in combined defect subjects.
   ConclusionsThe study confirms that in people with visual impairment the reduced reading performance is correlated with fixation instability. Moreover, there is a strong relationship between reading speed and both the proportion of fixations falling within 2 degrees and 4 degrees and bivariate contour ellipse area values.
C1 [Amore, Filippo M.; Silvestri, Valeria; Cruciani, Filippo; Reibaldi, Alfredo] Natl Ctr Serv & Res Prevent Blindness & Rehabil L, Rome, Italy.
   [Fasciani, Romina] Univ Cattolica Sacro Cuore, Dept Ophthalmol, Rome, Italy.
   [Crossland, Michael D.] UCL Inst Ophthalmol, London, England.
   [Crossland, Michael D.] Moorfields Eye Hosp NHS Fdn Trust, London, England.
   [de Waure, Chiara] Univ Cattolica Sacro Cuore, Inst Hyg, Rome, Italy.
C3 Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli;
   University of London; University College London; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli
RP Amore, FM (通讯作者)，Natl Ctr Serv & Res Prevent Blindness & Rehabil L, Rome, Italy.
EM f.amore@iapb.it
RI Silvestri, Valeria/AAB-9530-2022; Dewaure, Chiara/K-7192-2016;
   Crossland, Michael D/B-5600-2008
OI Dewaure, Chiara/0000-0002-4346-1494; Crossland, Michael
   D/0000-0001-6833-6043; Silvestri, Valeria/0000-0002-8451-8901
FU National Institute for Health Research [PDF/01/2008/011]
FX MDC is supported by the National Institute for Health Research grant
   PDF/01/2008/011. The views expressed in this publication are those of
   the authors and not necessarily those of the NHS, the National Institute
   for Health Research or the Department of Health.
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NR 43
TC 41
Z9 41
U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-5408
EI 1475-1313
J9 OPHTHAL PHYSL OPT
JI Ophthalmic Physiol. Opt.
PD SEP
PY 2013
VL 33
IS 5
BP 611
EP 617
DI 10.1111/opo.12048
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 283XM
UT WOS:000329280300008
PM 23489240
DA 2022-11-30
ER

PT J
AU Ramkumar, HL
   Tuo, JS
   Shen, DF
   Zhang, J
   Cao, XG
   Chew, EY
   Chan, CC
AF Ramkumar, Hema L.
   Tuo, Jingsheng
   Shen, De F.
   Zhang, Jun
   Cao, Xiaoguang
   Chew, Emily Y.
   Chan, Chi-Chao
TI Nutrient Supplementation with n3 Polyunsaturated Fatty Acids, Lutein,
   and Zeaxanthin Decrease A2E Accumulation and VEGF Expression in the
   Retinas of Ccl2/Cx3cr1-Deficient Mice on Crb1(rd8) Background
SO JOURNAL OF NUTRITION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; NITRIC-OXIDE; EYE
   DISEASE; MODEL; CAROTENOIDS; LIPOFUSCIN; LESIONS; NEOVASCULARIZATION;
   PROGRESSION
AB The Age-Related Eye Diseases Study 2 (AREDS2) clinical trial is assessing the effects of higher dietary xanthophyll (lutein and zeaxanthin) and long-chain n3 polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake on progression to advanced age-related macular degeneration (AMD). This study's purpose was to examine the retinal effects of the AREDS2 formulation on Chemokine (C-C motif) ligand 2 (Ccl2(-/-))/CX3C chemokine receptor 1 (Cx3cr1(-/-)) mice on Crumbs homolog 1 retinal degeneration phenotype 8 (Crb1(rd8)) background (DKO), which develop focal retinal lesions with certain features similar to AMD. DKO and C57BL/6N rd8 background mice (WT) were bred and randomized into 4 groups. Two groups, WT mice on AREDS2 diet (A-WT) and DKO mice on AREDS2 diet (A-DKO), were supplemented daily with 1.76 mu mol of lutein, 35.1 mu mol of zeaxanthin, 215 mu mol EPA, and 107 mu mol of DHA, and 2 control groups, WT mice on control diet (C-WT) and DKO mice on control diet (C-DKO), were fed an isocaloric diet. All mice had monthly fundus photos and were killed after 3 mo for biochemical and histologic analyses. After 3 mo, 81% of A-DKO mice had lesion regression compared with 25% of C-DKO mice (P < 0.05). Toxic retinal 2-[2,6-dimethyl-8(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetra-enyl]-1-(2-hydroxyethyl)-4[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl) 1E,3E,5E,7E-hexatrienyl]-pyridinium (A2E) concentrations were significantly lower in A-DKO compared with C-DKO mice. The outer nuclear layer thickness in A-DKO mice was significantly greater than that in C-DKO mice. Retinal expression of inducible nitric oxide synthase (iNos) tumor necrosis factor-alpha (Tnf-alpha), Cyclooxygenase-2 (Cox-2), interleukin1beta (IL-1 beta), and vascular endothelial growth factor (Vegf) was significantly lower in A-DKO compared with C-DKO mice. Xanthophylls and LCPUFAs have antiinflammatory, neuroprotective, and antiangiogenic properties. Our data provide potential mechanisms by which the AREDS2 formula has a protective effect on retinal lesions in DKO mice.
C1 [Ramkumar, Hema L.; Tuo, Jingsheng; Shen, De F.; Cao, Xiaoguang; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Zhang, Jun; Chan, Chi-Chao] NEI, Histol Core, NIH, Bethesda, MD 20892 USA.
   [Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA.
   [Ramkumar, Hema L.] Howard Hughes Med Inst, Chevy Chase, MD USA.
   [Ramkumar, Hema L.] Univ Calif San Diego, Dept Ophthalmol, Shiley Eye Ctr, San Diego, CA 92103 USA.
   [Cao, Xiaoguang] Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); National Institutes of Health (NIH) - USA; NIH National Eye
   Institute (NEI); National Institutes of Health (NIH) - USA; NIH National
   Eye Institute (NEI); Howard Hughes Medical Institute; University of
   California System; University of California San Diego; Peking University
RP Chan, CC (通讯作者)，NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
OI Tuo, Jingsheng/0000-0002-1372-7810
FU Intramural Research Program of the National Eye Institute; NIH; Howard
   Hughes Medical Institute; NATIONAL EYE INSTITUTE [ZIAEY000222,
   ZICEY000461, ZIAEY000418] Funding Source: NIH RePORTER
FX Supported by the Intramural Research Program of the National Eye
   Institute, NIH, and Howard Hughes Medical Institute.
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NR 52
TC 46
Z9 47
U1 1
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD JUL
PY 2013
VL 143
IS 7
BP 1129
EP 1135
DI 10.3945/jn.112.169649
PG 7
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 170ZT
UT WOS:000320894800016
PM 23677863
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Bian, QN
   Gao, SS
   Zhou, JL
   Qin, J
   Taylor, A
   Johnson, EJ
   Tang, GW
   Sparrow, JR
   Gierhart, D
   Shang, F
AF Bian, Qingning
   Gao, Shasha
   Zhou, Jilin
   Qin, Jian
   Taylor, Allen
   Johnson, Elizabeth J.
   Tang, Guangwen
   Sparrow, Janet R.
   Gierhart, Dennis
   Shang, Fu
TI Lutein and zeaxanthin supplementation reduces photooxidative damage and
   modulates the expression of inflammation-related genes in retinal
   pigment epithelial cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Lutein; Zeaxanthin; RPE; Photooxidation; Proteasome; Inflammation
ID COMPLEMENT FACTOR-H; NF-KAPPA-B; C-REACTIVE PROTEIN;
   UBIQUITIN-PROTEASOME PATHWAY; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; OXIDATIVE STRESS; ENDOTHELIAL-CELLS; CONJUGATING ENZYMES;
   PROTEOLYTIC PATHWAY
AB Oxidative damage and inflammation are related to the pathogenesis of age-related macular degeneration (AMD). Epidemiologic studies suggest that insufficient dietary lutein and zeaxanthin intake or lower serum zeaxanthin levels are associated with increased risk for AMD. The objective of this work is to test the protective effects of lutein and zeaxanthin against photooxidative damage to retinal pigment epithelial cells (RPE) and oxidation-induced changes in expression of inflammation-related genes. To mimic lipofuscin-mediated photooxidation in vivo, we used ARPE-19 cells that accumulated A2E, a lipofuscin fluorophore and photosensitizer, as a model system to investigate the effects of lutein and, zeaxanthin supplementation. The data show that supplementation with lutein or zeaxanthin in the medium resulted in accumulation of lutein or zeaxanthin in the RPE cells. The concentrations of lutein and zeaxanthin in the cells were 2- to 14-fold of that detected in the medium, indicating that ARPE-19 cells actively take up lutein or zeaxanthin. As compared with untreated cells, exposure of A2E-containing RPE to blue light resulted in a 40-60% decrease in proteasome activity, a 50-80% decrease in expression of CFH and MCP-1, and an similar to 20-fold increase in expression of IL-8. The photooxidation-induced changes in expression of MCP-1, IL-8, and CFH were similar to those caused by chemical inhibition of the proteasome, suggesting that inactivation of the proteasome is involved in the photooxidation-induced alteration in expression of these inflammation-related genes. Incubation of the A2E-containing RPE with lutein or zeaxanthin prior to blue light exposure significantly attenuated the photooxidation-induced inactivation of the proteasome and photooxidation-induced changes in expression of MCP-1, IL-8, and CFH. Together, these data indicate that lutein or zeaxanthin modulates inflammatory responses in cultured RPE in response to photooxidation. Protecting the proteasome from oxidative inactivation appears to be one of the mechanisms by which lutein and zeaxanthin modulate the inflammatory response. Similar mechanisms may explain salutary effects of lutein and zeaxanthin in reducing the risk for AMD. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Bian, Qingning; Gao, Shasha; Qin, Jian; Taylor, Allen; Johnson, Elizabeth J.; Tang, Guangwen; Shang, Fu] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   [Bian, Qingning; Gao, Shasha; Shang, Fu] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
   [Zhou, Jilin; Sparrow, Janet R.] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   [Gierhart, Dennis] Zeavision LLC, Chesterfield, MO 63005 USA.
C3 Tufts University; United States Department of Agriculture (USDA); Sun
   Yat Sen University; Columbia University
RP Shang, F (通讯作者)，Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
EM fu.shang@tufts.edu
FU USDA AFRI Award [2009-35200-05014]; NIH Grant [EY 011717]; USDA Contract
   [1950-510000-060-01A]; Dennis L. Gierhart Charitable Gift Fund; NATIONAL
   EYE INSTITUTE [R01EY011717, R29EY011717, R01EY013250, R01EY021212,
   R01EY012951, P30EY019007] Funding Source: NIH RePORTER
FX This work is supported by USDA AFRI Award 2009-35200-05014, NIH Grant EY
   011717, USDA Contract 1950-510000-060-01A, and Dennis L. Gierhart
   Charitable Gift Fund.
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NR 111
TC 155
Z9 162
U1 1
U2 69
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD SEP 15
PY 2012
VL 53
IS 6
BP 1298
EP 1307
DI 10.1016/j.freeradbiomed.2012.06.024
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 007QS
UT WOS:000308903800009
PM 22732187
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Guo, JH
   Wang, H
   Hrinczenko, B
   Salomon, RG
AF Guo, Junhong
   Wang, Hua
   Hrinczenko, Borys
   Salomon, Robert G.
TI Efficient Quantitative Analysis of Carboxyalkylpyrrole Ethanolamine
   Phospholipids: Elevated Levels in Sickle Cell Disease Blood
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; OXIDATIVE STRESS;
   OXIDIZED PHOSPHOLIPIDS; ENDOGENOUS LIGANDS; CRITICAL INSIGHTS; COVALENT
   BINDING; PROTEIN ADDUCTS; BASIC RESEARCH; PHOSPHATIDYLETHANOLAMINE
AB gamma-Hydroxy-alpha,beta-unsaturated aldehydes, generated by oxidative damage of polyunsaturated phospholipids, form pyrrole derivatives that incorporate the ethanolamine phospholipid (EP) amino group such as 2-pentylpyrrole (PP)-EP and 2-(co-carboxyalkyl)pyrrole (CAP)-EP derivatives: 2(omega-carboxyethyl)pyrrole (CEP) -EP, 2-(co-carbOx-ypropy1)pyrrole (CPP)-EP, and 2-(co-carboxyheptyppyrrole (CHP)EP. Because EPs occur in vivo in various forms, a complex mixture of pyrrole-modified EPs with. different molecular weights is expected to be generated. To provide a sensitive index of oxidative stress, all of the differences in mass related to the glycerophospholipid moieties were removed by releasing a single CAP-ethanolamine (ETN) or PP-ETN from each mixture by treatment with phospholipase D. Accurate quantization was. achieved using, the corresponding ethanolamine-d(4) pyrroles as internal standards. The product mixture obtained by phospholipolysis of total blood phospholipids from sickle cell disease (SCD) patients was analyzed by LC-MS/MS. The method was:applied to measure CAP-EP and PP-EP levels in blood plasma from clinical monitoring of SCD patients. We found uniformly elevated blood levels of CEP-EP (63.9 +/- 9.7 nM) similar to mean levels in blood from age-related macular degeneration (AMD) patients (56.3 +/- 37.1 nM), and 2-fold lower levels (27.6 (+/-) 3.6 nM, n = 5) were detected in plasma from SCD patients hospitalized to treat a sickle cell crisis, although mean levels remain higher than those (12.1 +/- 10.5 nM) detected in blood from healthy controls. Plasma levels of CPP-EPs from SCD clinic patients were 4-fold higher than those of SCD patients hospitalized to treat a sickle cell crisis (45.1 +/- 0.92 nM, n = S versus 10.9 +/- 3.4 nM, n = 6; p < 0.002). PP -EP concentration in plasma from SCD clinic patients is nearly 4.8 -fold higher than its level in plasma samples from SCD patients hospitalized to treat a sickle cell crisis (7.06 +/- 4.05 vs 1.48 +/- 0.92 nM; p < 0:05). Because CAP-EPs promote angiogenesis and platelet activation, the elevated levels present in SCD blood" can contribute to the hypercoaguability and Vaso-occlusive events that are critical pathophysiologic features of SCD.
C1 [Guo, Junhong; Wang, Hua; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
   [Hrinczenko, Borys] Michigan State Univ, Div Hematol & Oncol, E Lansing, MI 48824 USA.
C3 Case Western Reserve University; Michigan State University
RP Salomon, RG (通讯作者)，Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
EM rgs@case.edu
RI Guo, Junhong/O-6316-2017
OI Guo, Junhong/0000-0003-0005-4837; Salomon, Robert/0000-0001-9456-3557
FU NIH [EY016813, GM021249]; NATIONAL EYE INSTITUTE [P30EY011373,
   R01EY016813] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL
   MEDICAL SCIENCES [R01GM021249] Funding Source: NIH RePORTER
FX This work was supported by NIH Grants EY016813 and GM021249 to RGS.
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NR 43
TC 4
Z9 4
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
EI 1520-5010
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD JUL
PY 2016
VL 29
IS 7
BP 1187
EP 1197
DI 10.1021/acs.chemrestox.6b00152
PG 11
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA DR8XQ
UT WOS:000380182100012
PM 27341308
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Sarraf, D
   Chan, C
   Rahimy, E
   Abraham, P
AF Sarraf, David
   Chan, Clement
   Rahimy, Ehsan
   Abraham, Prema
TI PROSPECTIVE EVALUATION OF THE INCIDENCE AND RISK FACTORS FOR THE
   DEVELOPMENT OF RPE TEARS AFTER HIGH- AND LOW-DOSE RANIBIZUMAB THERAPY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; antivascular endothelial growth
   factor; ranibizumab; retinal pigment epithelial tears; vascularized
   pigment epithelial detachment
ID PIGMENT EPITHELIAL TEAR; INTRAVITREAL BEVACIZUMAB INJECTION; OPTICAL
   COHERENCE TOMOGRAPHY; CHOROIDAL NEOVASCULARIZATION SECONDARY;
   PROLIFERATIVE DIABETIC-RETINOPATHY; MACULAR DEGENERATION;
   CLINICOPATHOLOGICAL CORRELATION; RETINAL-DETACHMENT; AVASTIN;
   PATHOGENESIS
AB Purpose: To prospectively determine the incidence and risk factors for retinal pigment epithelial (RPE) tears in eyes with vascularized pigment epithelial detachments (PED) and exudative age-related macular degeneration receiving antivascular endothelial growth factor therapy.
   Methods: Eyes were prospectively randomized into 1 of 4 arms: 1) 0.5 mg of ranibizumab monthly for 12 months; 2) 0.5 mg of ranibizumab monthly for 3 months and then pro re nata on the basis of clinical and optical coherence tomography-guided indications; 3) high-dose 2.0 mg of ranibizumab monthly for 12 months; or 4) 2.0 mg of ranibizumab monthly for 3 months and then pro re nata thereafter. All PEDs were measured for height, greatest linear diameter, and surface area at baseline. The incidence of RPE tears in the entire 4-arm cohort was determined at the end of 12 months. Eyes were divided into two groups (tear vs. nontear) and statistically compared to determine risk factors for the development of RPE tear.
   Results: Of 37 eyes, a total of 5 developed postranibizumab RPE tears during the course of the study (incidence 14%). Four of the 5 tears occurred in the high-dose 2.0-mg groups. Baseline PED height, surface area, and greatest linear diameter were significantly greater in the group that developed RPE tears versus the nontear group (P = 0.018, 0.031, and 0.048, respectively). There were significantly more eyes with PED height >550 microns in the RPE tear group (4 of 5, 80%) compared with the nontear group (9 of 32, 18%) (P = 0.042). The presence of PED height >550 microns was associated with an increased tear rate from 14% to 31%. Furthermore, retrospective identification of a ring sign or Grade 1 tear at baseline, in addition to PED height >550 microns, was associated with a further increase in the tear rate to 67%.
   Conclusion: In this study, the prospective incidence of RPE tears was similar to 14%. A baseline PED height >550 microns and presence of a Grade 1 tear, or positive ring sign, were identified as high-risk factors for the subsequent development of an RPE tear.
C1 [Sarraf, David; Rahimy, Ehsan] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA.
   [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA.
   [Chan, Clement] Southern Calif Desert Retina Consultants, Med Grp, Palm Desert, CA USA.
   [Chan, Clement] Loma Linda Univ, Dept Ophthalmol, Loma Linda, CA 92350 USA.
   [Abraham, Prema] Black Hills Reg Eye Inst, Rapid City, SD USA.
C3 University of California System; University of California Los Angeles;
   US Department of Veterans Affairs; Veterans Health Administration (VHA);
   VA Greater Los Angeles Healthcare System; Loma Linda University
RP Sarraf, D (通讯作者)，Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, 100 Stein Plaza, Los Angeles, CA 90095 USA.
EM dsarraf@ucla.edu
OI Rahimy, Ehsan/0000-0001-8446-7078
FU Genentech; Karl Kirchgessner Foundation at the Jules Stein Eye Institute
FX Supported by an Investigator-Supported Trial grant from Genentech and by
   a grant (D. S.) from the Karl Kirchgessner Foundation at the Jules Stein
   Eye Institute.
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NR 51
TC 47
Z9 48
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD SEP
PY 2013
VL 33
IS 8
BP 1551
EP 1557
DI 10.1097/IAE.0b013e31828992f5
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 297CP
UT WOS:000330233200009
PM 23652578
DA 2022-11-30
ER

PT J
AU Jansen, RM
   Gouws, C
AF Jansen, Rita-Marie
   Gouws, Chris
TI Clinical, legal and ethical implications of the intra-ocular (off-label)
   use of bevacizumab (Avastin) - a South African perspective
SO SAMJ SOUTH AFRICAN MEDICAL JOURNAL
LA English
DT Article
ID INTRAVITREAL BEVACIZUMAB; MACULAR DEGENERATION
AB Choroidal neovascularisation is a potentially visually devastating element of various forms of eye pathology. Recent research has focused on neurovascular age-related macular degeneration (AMD) as a cause. AMD can be classified as being exudative (wet) or atrophic (dry). Wet AMD is characterised by a pathological process in which new blood vessels develop in the choroids, causing leakage of fluid and haemorrhage under the retina and leading to localised serous detachment and loss of central vision. Vascular endothelial growth factor (VEGF) stimulates growth of neovascular membranes. Treatments have until recently yielded disappointing results.
   Ophthalmologists are using intra-ocular injections of bevacizumab (Avastin), an anti-VEGF, to treat AMD. Avastin appears to be safe and effective in the short term, but its intraocular administration is entirely off-label. Avastin is registered for treating metastatic colorectal and breast cancer.
   The off-label use of medication is an important part of mainstream, legitimate medical practice worldwide. Lawyers representing plaintiffs injured by drugs increasingly encounter off-label use claims. From a legal/ethical point of view the off-label use of medication represents a delicate balance between the statutory regulation of medication and a physician's prerogative to prescribe medication that in his or her medical opinion will be beneficial to the patient. The main reason for the controversy created by the off-label use of Avastin is that there are anti-VEGF drugs on the market that have formal approval for the treatment of AMD (and other eye conditions). Lucentis, for example, is extremely expensive, with treatment cost approximately 50 times that of Avastin. Many patients suffering from AMD and macular oedema cannot afford the registered product.
   The off-label use of Avastin has passed the innovative or experimental stages, as ophthalmologists have used it regularly and openly for a long time, with good success. Such use therefore cannot be considered careless, imprudent or unprofessional. We submit that an ophthalmologist who omits to inform a patient of the availability of Avastin for this form of treatment may be found to be negligent.
   Protocols developed by the South African Vitreoretinal Society and endorsed by the Ophthalmological Society of South Africa for administering Avastin and other intra-ocular medication intravitreally should be strictly adhered to.
C1 [Jansen, Rita-Marie] Univ Orange Free State, Dept Private Law, Bloemfontein, South Africa.
   [Gouws, Chris] Hosp Pk, Bloemfontein Eye Ctr, Bloemfontein, South Africa.
C3 University of the Free State
RP Jansen, RM (通讯作者)，Univ Orange Free State, Dept Private Law, Bloemfontein, South Africa.
EM jansen.rd@ufs.ac.za
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NR 23
TC 5
Z9 7
U1 0
U2 2
PU SA MEDICAL ASSOC
PI PRETORIA
PA BLOCK F CASTLE WALK CORPORATE PARK, NOSSOB STREET, ERASMUSKLOOF EXT3,
   PRETORIA, 0002, SOUTH AFRICA
SN 0256-9574
J9 SAMJ S AFR MED J
JI SAMJ S. Afr. Med. J.
PD JUN
PY 2009
VL 99
IS 6
BP 446
EP 449
PG 4
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 463MD
UT WOS:000267435400016
PM 19736847
DA 2022-11-30
ER

PT J
AU Praddaude, F
   Cousins, SW
   Pecher, C
   Marin-Castano, ME
AF Praddaude, Francoise
   Cousins, Scott W.
   Pecher, Christiane
   Marin-Castano, Maria E.
TI Angiotensin II-induced hypertension regulates AT1 receptor subtypes and
   extracellular matrix turnover in mouse retinal pigment epithelium
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE hypertension; angiotensin II receptors; age-related macular
   degeneration; retinal pigment epithelium; calcium; matrix
   metalloproteinases; collagen type IV
ID NONLETHAL OXIDANT INJURY; RENIN MESSENGER-RNA; CONVERTING ENZYME; TIMP-1
   EXPRESSION; TISSUE INHIBITOR; GENE-EXPRESSION; AT(1) RECEPTOR; CELLS;
   RPE; METALLOPROTEINASE
AB Accumulation of specific deposits and extracellular molecules under the retinal pigment epithelium (RPE) has been previously observed in eyes with age-related macular degeneration (AMD) and may play a role in the pathogenesis of AMD. Even though age is the major determinant for developing AMD, clinical studies have revealed hypertension (HTN) as another systemic risk factor. Angiotensin II (Ang II) is considered the most important hormone associated with HTN. To evaluate the relationship of Ang II to AMD, we studied whether mouse RPE expresses functional Ang II receptor subtypes and whether HTN-induced Ang II regulates expression of these receptors as well as critical ECM molecules (MMP-2 and type IV collagen) involved in ECM turnover in RPE. We used 9-month-old C57BL/6 male mice infused with Ang II alone or Ang II in combination with the AT1 receptor antagonist candesartan or the AT2 receptor antagonist PD123319 for 4 weeks to determine whether HTN-associated Ang II was important for ECM regulation in RPE. We found that mouse RPE expressed both Ang II receptor subtypes at the mRNA and protein levels. Infusion with Ang II induced HTN and elevated plasma and ocular Ang II levels. Ang II also regulated AT1 a and AT1b receptor mRNA expression, the intracellular concentration of calcium [Ca2+](i), MMP-2 activity, and type IV collagen accumulation. Concurrent administration of Ang II with the AT1 receptor blocker prevented the increase in blood pressure and rise in ocular Ang II levels, as well as the calcium and MMP-2 responses. In contrast, the type IV collagen response to Ang II was prevented by blockade of AT2 receptors, but not AT1 receptors. Plasma Ang II levels were not modified by the AT1 or AT2 receptor blockade. Since the effects of Ang II on MMP-2 and type IV collagen require inhibition of both Ang II receptor subtypes, these receptors may play a role as a potential therapeutic targets to prevent ECM turnover dysregulation in the RPE basement membrane, suggesting a pathogenic mechanism to explain the link between HTN and AMD. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Marin-Castano, Maria E.] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Praddaude, Francoise; Pecher, Christiane] Univ Toulouse 3, Sch Med, F-31062 Toulouse, France.
   [Cousins, Scott W.] Duke Univ, Ctr Eye, Duke Ctr Macular Dis, Durham, NC USA.
C3 Bascom Palmer Eye Institute; University of Miami; Universite de
   Franche-Comte; Universite de Toulouse; Universite Toulouse III - Paul
   Sabatier; Duke University
RP Marin-Castano, ME (通讯作者)，Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami, FL 33136 USA.
EM mcastano@med.miami.edu
FU NIH [EY015249-01A1]; NEI P30 Core [NEI P30 Core Grant EY014801];
   Research to Prevent Blindness; NATIONAL EYE INSTITUTE [P30EY014801,
   R01EY015249] Funding Source: NIH RePORTER
FX The authors thank Drs. Oscar Alcazar, Marianne Pons, and Colleen Cebulla
   for critical reading of the manuscript. Dr. Min-Sheng Zhou's technical
   support is appreciated. This work was supported by the NIH grant
   EY015249-01A1, NEI P30 Core Grant EY014801, and an unrestricted grant
   from Research to Prevent Blindness to the University of Miami.
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NR 67
TC 22
Z9 26
U1 0
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUN
PY 2009
VL 89
IS 1
BP 109
EP 118
DI 10.1016/j.exer.2009.02.020
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 456SS
UT WOS:000266869200014
PM 19281810
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Ming, Y
   Algvere, PV
   Odergren, A
   Berglin, L
   van der Ploeg, I
   Seregard, S
   Kvanta, A
AF Ming, Y
   Algvere, PV
   Odergren, A
   Berglin, L
   van der Ploeg, I
   Seregard, S
   Kvanta, A
TI Subthreshold transpupillary thermotherapy reduces experimental choroidal
   neovascularization in the mouse without collateral damage to the neural
   retina
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MACULAR DEGENERATION; PHOTODYNAMIC THERAPY
AB PURPOSE. Transpupillary thermotherapy (TTT) is currently being evaluated for treatment of choroidal neovascularization (CNV) in age-related macular degeneration. To optimize TTT for CNV, the effect was analyzed of invisible (subthreshold) or visible (threshold) doses of TTT on the normal mouse retina and on experimental CNV.
   METHODS. TTT was delivered to the normal retina of 42 mice with a diode laser at increasing power settings (50, 60, 70, or 80 mW), to obtain thermal lesions ranging from invisible (subthreshold) to visible (threshold) burns. CNV was induced in 53 mice by krypton laser photocoagulation of the fundus, after which the CNV lesions were treated with TTT (50, 60, or 80 mW). Eyes were enucleated 7 days after TTT and prepared for histology, and the CNV complex was evaluated on hematoxylin-eosin stained serial sections by measuring the maximum height of the CNV lesions. Ultrastructural changes were examined by transmission electron microscopy.
   RESULTS. Increasing the TTT laser power yielded gradually more visible effects. At 50 mW, which induced subthreshold burns, no damage was seen in the neural retina, retinal pigment epithelium (RPE), or choroid at any time point. By contrast, eyes treated with higher power exhibited progressively more damage to the neural retina, including a complete disruption of the outer nuclear layer. When TTT was applied to the laser-induced CNV lesions, the height of lesions was significantly reduced (P < 0.001) in response to all three power settings at 7 days after treatment. The mean relative thickness of the CNV lesion was 3.29 +/- 0.89 in untreated mice, whereas in TTT-treated mice it was 1.69 +/- 0.35, 1.69 +/- 0.41 and 1.70 +/- 0.17 at power settings of 50, 60, and 80 mW, respectively. The overlying neural retina showed no apparent damage with the 50- or 60-mW settings, whereas outer nuclear layer disruption occurred with a power of 80 mW. Electron microscopy confirmed the presence of vascular occlusion at I (lay and a fibrotic sear at 7 days after TTT.
   CONCLUSIONS. Subthreshold TTT can effectively occlude newly formed vessels and cause regression of the experimental CNV complex without damaging the neural retina. The results demonstrate the importance of using subthreshold laser power in experimental and clinical evaluation of TTT.
C1 St Eriks Eye Hosp, Karolinska Inst, Dept Ophthalmol, SE-11282 Stockholm, Sweden.
   St Eriks Eye Hosp, Karolinska Inst, Dept Physiol & Pharmacol, SE-11282 Stockholm, Sweden.
   Jilin Univ, Hosp 2, Dept Ophthalmol, Changchun 130023, Peoples R China.
C3 Karolinska Institutet; Karolinska Institutet; Jilin University
RP Kvanta, A (通讯作者)，St Eriks Eye Hosp, Karolinska Inst, Dept Ophthalmol, Polhemsgatan 50, SE-11282 Stockholm, Sweden.
EM anders.kvanta@sankterik.se
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NR 25
TC 31
Z9 36
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2004
VL 45
IS 6
BP 1969
EP 1974
DI 10.1167/iovs.03-1329
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 824EO
UT WOS:000221668900045
PM 15161865
DA 2022-11-30
ER

PT J
AU Rim, TH
   Teo, AWJ
   Yang, HHS
   Cheung, CY
   Wong, TY
AF Rim, Tyler Hyungtaek
   Teo, Alvin Wei Jun
   Yang, Henrik Hee Seung
   Cheung, Carol Y.
   Wong, Tien Yin
TI Retinal Vascular Signs and Cerebrovascular Diseases
SO JOURNAL OF NEURO-OPHTHALMOLOGY
LA English
DT Article
ID SMALL VESSEL DISEASE; SILENT BRAIN INFARCTION; ACUTE CORONARY SYNDROME;
   ACUTE ISCHEMIC-STROKE; MICROVASCULAR ABNORMALITIES;
   DIABETIC-RETINOPATHY; ATHEROSCLEROSIS RISK; MACULAR DEGENERATION;
   ARTERY-OCCLUSION; CARDIOVASCULAR-DISEASE
AB Background: Cerebrovascular disease (CeVD), including stroke, is a leading cause of death globally. The retina is an extension of the cerebrum, sharing embryological and vascular pathways. The association between different retinal signs and CeVD has been extensively evaluated. In this review, we summarize recent studies which have examined this association. Evidence Acquisition: We searched 6 databases through July 2019 for studies evaluating the link between retinal vascular signs and diseases with CeVD. CeVD was classified into 2 groups: clinical CeVD (including clinical stroke, silent cerebral infarction, cerebral hemorrhage, and stroke mortality), and sub-clinical CeVD (including MRI-defined lacunar infarct and white matter lesions [WMLs]). Retinal vascular signs were classified into 3 groups: classic hypertensive retinopathy (including retinal microaneurysms, retinal microhemorrhage, focal/generalized arteriolar narrowing, cotton-wool spots, and arteriovenous nicking), clinical retinal diseases (including diabetic retinopathy [DR], age-related macular degeneration [AMD], retinal vein occlusion, retinal artery occlusion [RAO], and retinal emboli), and retinal vascular imaging measures (including retinal vessel diameter and geometry). We also examined emerging retinal vascular imaging measures and the use of artificial intelligence (AI) deep learning (DL) techniques. Results: Hypertensive retinopathy signs were consistently associated with clinical CeVD and subclinical CeVD subtypes including subclinical cerebral large artery infarction, lacunar infarction, and WMLs. Some clinical retinal diseases such as DR, retinal arterial and venous occlusion, and transient monocular vision loss are consistently associated with clinical CeVD. There is an increased risk of recurrent stroke immediately after RAO. Less consistent associations are seen with AMD. Retinal vascular imaging using computer assisted, semi-automated software to measure retinal vascular caliber and other parameters (tortuosity, fractal dimension, and branching angle) has shown strong associations to clinical and subclinical CeVD. Other new retinal vascular imaging techniques (dynamic retinal vessel analysis, adaptive optics, and optical coherence tomography angiography) are emerging technologies in this field. Application of AI-DL is expected to detect subclinical retinal changes and discrete retinal features in predicting systemic conditions including CeVD. Conclusions: There is extensive and increasing evidence that a range of retinal vascular signs and disease are closely linked to CeVD, including subclinical and clinical CeVD. New technology including AI-DL will allow further translation to clinical utilization.
C1 [Rim, Tyler Hyungtaek; Teo, Alvin Wei Jun; Yang, Henrik Hee Seung; Wong, Tien Yin] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Rim, Tyler Hyungtaek; Wong, Tien Yin] Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore.
   [Cheung, Carol Y.] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Peoples R China.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; Chinese University of Hong Kong
RP Wong, TY (通讯作者)，Singapore Natl Eye Ctr, 11 Third Hosp Ave, Singapore 168751, Singapore.
EM wong.tien.yin@snec.com.sg
RI Wong, Tien Yin/AAC-9724-2020
OI Wong, Tien Yin/0000-0002-8448-1264
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NR 142
TC 24
Z9 29
U1 6
U2 21
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1070-8022
EI 1536-5166
J9 J NEURO-OPHTHALMOL
JI J. Neuro-Ophthal.
PD MAR
PY 2020
VL 40
IS 1
BP 44
EP 59
DI 10.1097/WNO.0000000000000888
PG 16
WC Clinical Neurology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology
GA LA9LZ
UT WOS:000524263100012
PM 31977663
OA Bronze
DA 2022-11-30
ER

PT J
AU Renner, M
   Stute, G
   Alzureiqi, M
   Reinhard, J
   Wiemann, S
   Schmid, H
   Faissner, A
   Dick, HB
   Joachim, SC
AF Renner, Marina
   Stute, Gesa
   Alzureiqi, Mohammad
   Reinhard, Jacqueline
   Wiemann, Susanne
   Schmid, Heiko
   Faissner, Andreas
   Dick, H. Burkhard
   Joachim, Stephanie C.
TI Optic Nerve Degeneration after Retinal Ischemia/Reperfusion in a Rodent
   Model
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Article
DE ischemia/reperfusion; retinal ischemia; optic nerve; microglia;
   macroglia; oligodendrocytes; neurofilament
ID AUTOIMMUNE GLAUCOMA MODEL; MYELIN OLIGODENDROCYTE GLYCOPROTEIN;
   PRESSURE-INDUCED ISCHEMIA; GANGLION-CELL DEATH; REPERFUSION INJURY; RAT
   RETINA; MULTIPLE-SCLEROSIS; NEUROLOGICAL DISEASES; MOLECULAR-MECHANISMS;
   CENTRAL ELEMENT
AB Retinal ischemia is a common pathomechanism in many ocular disorders such as age-related macular degeneration (AMD), diabetic retinopathy, glaucoma or retinal vascular occlusion. Several studies demonstrated that ischemia/reperfusion (I/R) leads to morphological and functional changes of different retinal cell types. However, little is known about the ischemic effects on the optic nerve. The goal of this study was to evaluate these effects. Ischemia was induced by raising the intraocular pressure (IOP) in one eye of rats to 140 mmHg for 1 h followed by natural reperfusion. After 21 days, histological as well as quantitative real-time PCR (qRT-PCR) analyses of optic nerves were performed. Ischemic optic nerves showed an infiltration of cells and also degeneration with signs of demyelination. Furthermore, a migration and an activation of microglia could be observed histologically as well as on mRNA level. In regard to macroglia, a trend toward gliosis could be noted after ischemia induction by vimentin staining. Additionally, an up-regulation of glial fibrillary acidic protein (GFAP) mRNA was found in ischemic optic nerves. Counting of oligodendrocyte transcription factor 2 positive (Olig2 C) cells revealed a decrease of oligodendrocytes in the ischemic group. Also, myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) mRNA expression was down-regulated after induction of I/R. On immunohistological level, a decrease of MOG was detectable in ischemic optic nerves as well. In addition, SMI-32 stained neurofilaments of longitudinal optic nerve sections showed a strong structural damage of the ischemic optic nerves in comparison to controls. Consequently, retinal ischemia impacts optic nerve degeneration. These findings could help to better understand the course of destruction in the optic nerve after an ischemic insult. Especially for therapeutic studies, the optic nerve is important because of its susceptibility to be damaged as a result to retinal ischemic injury and also its connecting function between the eye and the brain. So, future drug screenings should target not only the retina, but also the functionality and structure of the optic nerve. In the future, these results could lead to the development of new therapeutic strategies for treatment of ischemic injury.
C1 [Renner, Marina; Stute, Gesa; Alzureiqi, Mohammad; Schmid, Heiko; Dick, H. Burkhard; Joachim, Stephanie C.] Ruhr Univ Bochum, Univ Eye Hosp, Expt Eye Res, Bochum, Germany.
   [Reinhard, Jacqueline; Wiemann, Susanne; Faissner, Andreas] Ruhr Univ Bochum, Fac Biol & Biotechnol, Dept Cell Morphol & Mol Neurobiol, Bochum, Germany.
C3 Ruhr University Bochum; Ruhr University Bochum
RP Joachim, SC (通讯作者)，Ruhr Univ Bochum, Univ Eye Hosp, Expt Eye Res, Bochum, Germany.
EM stephanie.joachim@rub.de
RI Joachim, Stephanie/AAV-5980-2021; Faissner, Andreas/A-5314-2008; Dick,
   Burkhard/AAI-7504-2020
OI Faissner, Andreas/0000-0002-2211-8259; Reinhard,
   Jacqueline/0000-0002-4227-0493
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NR 51
TC 49
Z9 50
U1 0
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
   SWITZERLAND
SN 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD AUG 22
PY 2017
VL 11
AR 254
DI 10.3389/fncel.2017.00254
PG 11
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA FE4DZ
UT WOS:000408165900002
PM 28878627
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Reynolds, R
   Rosner, B
   Seddon, JM
AF Reynolds, Robyn
   Rosner, Bernard
   Seddon, Johanna M.
TI Dietary Omega-3 Fatty Acids, Other Fat Intake, Genetic Susceptibility,
   and Progression to Incident Geographic Atrophy
SO OPHTHALMOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; C-REACTIVE PROTEIN; MITOCHONDRIAL-DNA HAPLOGROUPS;
   GENOME-WIDE ASSOCIATION; MACULAR DEGENERATION; CIGARETTE-SMOKING; FISH
   CONSUMPTION; EYE DISEASE; RISK; ARMS2
AB Objective: To investigate associations between dietary omega-3 fatty acids and other fat intake, genes related to age-related macular degeneration (AMD), and progression to geographic atrophy (GA).
   Design: Observational analysis of a prospective cohort.
   Participants: A total of 2531 individuals from the Age-Related Eye Disease Study, among which 525 eyes progressed to GA and 4165 eyes did not.
   Methods: Eyes without advanced AMD at baseline were evaluated for progression to GA. Behavioral data, including smoking and body mass index measurements, were collected at baseline using questionnaires. Dietary data were collected from food frequency questionnaires (FFQs) at baseline. Omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]), omega-6 fatty acids, monounsaturated, saturated, polyunsaturated, and total fat were adjusted for sex and calories and divided into quintiles (Q). Eight single nucleotide polymorphisms in 7 genes (CFH, ARMS2/HTRA1, CFB, C2, C3, CFI, and LIPC) were genotyped. Cox proportional hazards models were used to test for associations between incident GA and intake of dietary lipids and interaction effects between dietary fat intake and genetic variation on risk of GA.
   Main Outcome Measures: Associations between dietary fat intake reported from FFQs, genetic variants, and incident GA.
   Results: Increased intake of DHA was significantly associated with reduced risk of progression to GA in models with behavioral factors (model A) plus genetic variants (model B) (P trend = 0.01 and 0.03, respectively). Total omega-3 long chain polyunsaturated (DHA + EPA) fatty acid intake was significantly associated with reduced risk of progression in model B (P trend = 0.02). Monounsaturated fat was associated with increased risk in model A (P trend = 0.05). DHA intake was significantly associated with reduced risk of incident GA among those with the ARMS2/HTRA1 homozygous risk genotype (hazard ratio [HR] Q5 vs Q1, 0.4; P = 0.002; P for interaction between gene and fat intake = 0.05). DHA was not associated with reduced risk of GA among those with the homozygous ARMS2/HTRA1 nonrisk genotype (HR, 1.0; P = 0.90).
   Conclusions: Increased self-reported dietary intake of omega-3 fatty acids is associated with reduced risk of GA and may modify genetic susceptibility for progression to GA.
C1 [Reynolds, Robyn; Seddon, Johanna M.] Tufts Med Ctr, Dept Ophthalmol, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA.
   [Rosner, Bernard] Channing Labs, Boston, MA USA.
   [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
C3 Tufts Medical Center; Tufts University
RP Seddon, JM (通讯作者)，Tufts Med Ctr, 800 Washington St 450, Boston, MA 02111 USA.
EM jseddon@tuftsmedicalcenter.org
RI Mitchell, Paul/P-1498-2014
FU National Institutes of Health (Bethesda, MD) [R01-EY11309];
   Massachusetts Lions Eye Research Fund, Inc. (New Bedford, MA); Research
   to Prevent Blindness, Inc. (New York, NY); American Macular Degeneration
   Foundation (Northampton, MA); Macular Degeneration Research Fund of the
   Ophthalmic Epidemiology and Genetics Service (Boston, MA); New England
   Eye Center (Boston, MA); Tufts Medical Center (Boston, MA); Tufts
   University School of Medicine (Boston, MA); NATIONAL EYE INSTITUTE
   [R01EY011309] Funding Source: NIH RePORTER
FX Supported by in part by a grant R01-EY11309 from the National Institutes
   of Health (Bethesda, MD); Massachusetts Lions Eye Research Fund, Inc.
   (New Bedford, MA); an unrestricted grant from Research to Prevent
   Blindness, Inc. (New York, NY); the American Macular Degeneration
   Foundation (Northampton, MA); and the Macular Degeneration Research Fund
   of the Ophthalmic Epidemiology and Genetics Service, New England Eye
   Center, Tufts Medical Center, Tufts University School of Medicine
   (Boston, MA).
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NR 48
TC 59
Z9 61
U1 0
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAY
PY 2013
VL 120
IS 5
BP 1020
EP 1028
DI 10.1016/j.ophtha.2012.10.020
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 140VE
UT WOS:000318683400021
PM 23481534
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Chen, JZ
   Cao, DF
   Fortmann, SD
   Curcio, CA
   Feist, RM
   Crosson, JN
AF Chen, Jianzhong
   Cao, Dongfeng
   Fortmann, Seth D.
   Curcio, Christine A.
   Feist, Richard M.
   Crosson, Jason N.
TI Transthyretin proteoforms of intraocular origin in human subretinal
   fluid
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Subretinal fluid; Retinal detachment; Transthyretin; Posttranslational
   modification; Glutathionylation; Top -down proteomics; Single -cell RNA
   sequencing; Immunohistochemistry; Age -related macular degeneration;
   Mass spectrometry; Amyloidosis; Glycosylation; Interphotoreceptor
   matrix; ApolipoproteinA-I&nbsp; albumin
ID RETINOL-BINDING-PROTEIN; DOWN MASS-SPECTROMETRY; AMYLOID FIBRIL
   INHIBITORS; APOLIPOPROTEIN-A-I; OXIDATIVE STRESS; TOP-DOWN;
   SERUM-ALBUMIN; HUMAN PLASMA; COMPREHENSIVE ANALYSIS; MACULAR
   DEGENERATION
AB Understanding the molecular composition of ocular tissues and fluids could inform new approaches to prevalent causes of blindness. Subretinal fluid accumulating between the photoreceptor outer segments and retinal pigment epithelium (RPE) is potentially a rich source of proteins and lipids normally cycling among outer retinal cells and choroid. Herein, intact post-translationally modified proteins (proteoforms) were extracted from sub -retinal fluids of five patients with rhegmatogenous retinal detachment (RRD), analyzed by tandem mass spec-trometry, and compared to published data on these same proteins as synthesized by other organs. Single-nuclei transcriptomic data from non-diseased human retina/RPE were used to identify whether proteins in subretinal fluid were of potential ocular origin. Two human donor eyes with normal maculas were immunoprobed for transthyretin (TTR) with appropriate controls. The three most abundant proteins detected in subretinal fluid were albumin, TTR, and apolipoprotein A-I. Remarkably, TTR relative to the other proteins was more abundant than its serum counterpart, suggestive of TTR being synthesized predominantly locally. Six proteoforms of TTR were detected, with the relative amount of glutathionylated TTR being much higher in the subretinal fluid (12-43%) than values reported for serum (<5%) and cerebrospinal fluid (0.4-13%). Moreover, a putative gly-cosylated TTR dimer of 32,428 Da was detected as the fourth most abundant protein. The high abundance of TTR and putative TTR dimer in subretinal fluid was supported by analysis of available single-nuclei transcriptomic data, which showed strong and specific signal for TTR in RPE. Immunohistochemistry further showed strong diffuse TTR immunoreactivity in choroidal stroma that contrasted with vertically aligned signal in the outer segment zone of the subretinal space and negligible signal in RPE cell bodies. These results suggest that TTR in the retina is synthesized intraocularly, and glutathionylation is crucial for its normal function. Further studies on the composition, function, and quantities of TTR and other proteoforms in subretinal fluid could inform mechanisms, diagnostic methods, and treatment strategies for age-related macular degeneration, familial amyloidosis, and other retinal diseases involving dysregulation of physiologic lipid transfer and oxidative stress.
C1 [Chen, Jianzhong] Univ Alabama Birmingham, Dept Optometry & Vis Sci, Birmingham, AL 35294 USA.
   [Cao, Dongfeng; Fortmann, Seth D.; Curcio, Christine A.; Feist, Richard M.; Crosson, Jason N.] Univ Alabama Birmingham, Dept Ophthalmol & Visual Sci, Birmingham, AL 35294 USA.
   [Chen, Jianzhong] Cayman Chem Co, Ann Arbor, MI 48108 USA.
C3 University of Alabama System; University of Alabama Birmingham;
   University of Alabama System; University of Alabama Birmingham
RP Chen, JZ (通讯作者)，Univ Alabama Birmingham, Dept Optometry & Vis Sci, Birmingham, AL 35294 USA.; Curcio, CA (通讯作者)，Univ Alabama Birmingham, Dept Ophthalmol & Visual Sci, Birmingham, AL 35294 USA.; Chen, JZ (通讯作者)，Cayman Chem Co, Ann Arbor, MI 48108 USA.
EM jzchen@uab.edu; christinecurcio@uabmc.edu
RI Chen, Jianzhong/I-4450-2012
OI Chen, Jianzhong/0000-0001-5207-4798
FU NIH [R01EY0155203, F30EY033198]; Research to Prevent Blindness
FX The authors thank Dr. Xiaowen Liu and In Kwon Choi for their assistance
   with the use of the programs TopPIC and TopMSV, Dr. Lindsay Morrison and
   Dr. Peter Prevelige for their technical assistance with using the Synapt
   G2-Si mass spectrometer, and Jeffrey D. Messinger DC for retinal tissue
   preparation. This work is supported by NIH R01EY0155203 (CAC) , Research
   to Prevent Blindness (institutional support to UAB) , an anonymous donor
   to UAB for AMD research, and NIH F30EY033198 (SDF) .
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NR 107
TC 0
Z9 0
U1 2
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD SEP
PY 2022
VL 222
AR 109163
DI 10.1016/j.exer.2022.109163
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3E5ON
UT WOS:000830032700001
PM 35760119
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Pinelli, R
   Bertelli, M
   Scaffidi, E
   Bumah, VV
   Biagioni, F
   Busceti, CL
   Puglisi-Allegra, S
   Fornai, F
AF Pinelli, Roberto
   Bertelli, Miorica
   Scaffidi, Elena
   Bumah, Violet Vakunseth
   Biagioni, Francesca
   Busceti, Carla Letizia
   Puglisi-Allegra, Stefano
   Fornai, Francesco
TI The neurobiology of nutraceuticals combined with light exposure, a case
   report in the course of retinal degeneration
SO ARCHIVES ITALIENNES DE BIOLOGIE
LA English
DT Article
DE Photo-bio-modulation; Resveratrol; LuteinVaccinium Myrtillus; Bilberry;
   Autophagy; Mitochondria; Mitophagy; beta-amyloid; Age-related macular
   degeneration; Retinal pigment epithelium; Drusen
ID STEM-CELLS; VISUAL IMPAIRMENT; SNELLEN CHART; MULLER GLIA; AUTOPHAGY;
   AGE; RPE; PROLIFERATION; MECHANISMS; PHENOTYPES
AB The present article presents a case report and discusses the neurobiology underlying the potential neuro-repair induced by combined administration of phytochemicals in a patient undergoing photo-bio-modulation (PBM), which improves anatomical and clinical abnormalities in the course of age-related macular degeneration (AMD). After combined treatments the patient with nutraceuticals and PBM had noticeable improvement of retinal tissue with excellent vision for her age and no worsening of corneal guttae, which was present at the time of diagnosis. The present treatment was tailored, based on translational evidence, to improve the autophagy pathway, which is a key determinant in the onset and progression of AMD. In fact, treatment with specific patterns of light exposure combined with specific phytochemicals, may synergize in improving the microanatomy of the retina by restoring its neurobiology. The combination of light exposure, at selective wavelengths, with the effects produced by the intake of specific phytochemicals to treat AMD is reported here as "Lugano Protocol". Such a clinical protocol represents an "in progress" development backed up by translational research. In fact, recent evidence indicates that, specific phytochemicals, when administered in combination may promote anatomical and functional integrity within the retina. These in turn synergize with analogous effects produced by specific wavelengths, when administered at specific time intervals. The synergism between specific light and combined phytochemicals is discussed at molecular level, where recent data indicate how these treatments, when delivered according to specific patterns, may enhance autophagy in the retina. The improvement of retinal morphology and visual acuity, observed in this case report is thoroughly discussed in the light of the key role of autophagy in regulating the integrity of the retinal epithelium. Despite exciting, and consistent with translational evidence, the clinical report of a disease modifying effect during AMD owns the inherent limit of a case report, which requires wide validation in large number of patients. The potential effectiveness of "Lugano protocol" may apply to other types of retinal degenerations, where common alterations in the autophagy pathway do occur. Thus, such a therapeutic approach may extend to a common late stage of retinal trans-synaptic degeneration, where maladaptive plasticity during several types of retinal degenerative disorders eventually converge.
C1 [Pinelli, Roberto; Bertelli, Miorica; Scaffidi, Elena] Switzerland Eye Res Inst, Lugano, Switzerland.
   [Bumah, Violet Vakunseth] San Diego State Univ, Coll Sci, Dept Chem & Biochem, 5500 Campanile Dr, San Diego, CA 92782 USA.
   [Biagioni, Francesca; Busceti, Carla Letizia; Puglisi-Allegra, Stefano; Fornai, Francesco] IRCCS Neuromed Pozzili IS, Pozzilli, Italy.
   [Fornai, Francesco] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Pisa, Italy.
C3 California State University System; San Diego State University;
   University of Pisa
RP Fornai, F (通讯作者)，Univ Pisa, Dept Translat Res & New Technol Med & Surg, Human Anat, Via Roma 55, I-56126 Pisa, Italy.
EM francesco.fornai@unipi.it
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NR 90
TC 0
Z9 0
U1 1
U2 5
PU PISA UNIV PRESS
PI PISA
PA LUNGARNO A PACINOTTI 43, 56100 PISA, ITALY
SN 0003-9829
J9 ARCH ITAL BIOL
JI Arch. Ital. Biol.
PD DEC
PY 2021
VL 159
IS 3-4
BP 134
EP 150
DI 10.12871/000398292021343
PG 17
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA YP2YQ
UT WOS:000748492700003
PM 35077571
DA 2022-11-30
ER

PT J
AU Baumal, CR
   Spaide, RF
   Vajzovic, L
   Freund, KB
   Walter, SD
   John, V
   Rich, R
   Chaudhry, N
   Lakhanpal, RR
   Oellers, PR
   Leveque, TK
   Rutledge, BK
   Chittum, M
   Bacci, T
   Enriquez, AB
   Sund, NJ
   Subong, ENP
   Albini, TA
AF Baumal, Caroline R.
   Spaide, Richard F.
   Vajzovic, Lejla
   Freund, K. Bailey
   Walter, Scott D.
   John, Vishak
   Rich, Ryan
   Chaudhry, Nauman
   Lakhanpal, Rohit R.
   Oellers, Patrick R.
   Leveque, Thellea K.
   Rutledge, Bryan K.
   Chittum, Mark
   Bacci, Tommaso
   Enriquez, Ana Bety
   Sund, Newman J.
   Subong, Eric N. P.
   Albini, Thomas A.
TI Retinal Vasculitis and Intraocular Inflammation after Intravitreal
   Injection of Brolucizumab
SO OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; AFLIBERCEPT INJECTION; SAFETY
AB Purpose: To evaluate features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6 mg/0.05 ml for treatment of neovascular age-related macular degeneration.
   Design: Retrospective case series.
   Participants: Fifteen eyes from 12 patients identified from 10 United States centers.
   Methods: Review of patient demographics, ophthalmologic examination results, and retinal imaging findings.
   Main Outcome Measures: Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography results, and treatment strategies.
   Results: The number of previous anti-VEGF IVIs ranged between 2 and 80 in the affected eye before switching to brolucizumab. Retinal vasculitis and 101 were diagnosed at a mean of 30 days after brolucizumab IVI. Mean VA before brolucizumab IVI was 0.426 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/53) and VA at diagnosis of retinal vasculitis was 0.981 logMAR (Snellen equivalent, 20/191; range, 20/25-20/1600; P = 0 .008) . All affected eyes showed 101 with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages, and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular nonperfusion, and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients, and 3 patients showed negative laboratory assessment for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, and topical), and 2 eyes underwent vitrectomy without improvement in vision. After a mean follow-up of 25 days, mean VA was 0.833 logMAR (Snellen equivalent, 20/136), which was reduced compared with baseline (P = 0.033).
   Conclusions: Retinal vasculitis and IOI after brolucizumab IVI are characterized by variable occlusion of large or small retinal arteries, or both, and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required because vitreous cells may obscure visualization of retinal details. (C) 2020 by the American Academy of Ophthalmology
C1 [Baumal, Caroline R.; Enriquez, Ana Bety] Tufts Univ, New England Eye Ctr, Sch Med, Boston, MA USA.
   [Spaide, Richard F.; Freund, K. Bailey; Bacci, Tommaso] Vitreous Retina Macula Consultants New York, New York, NY USA.
   [Vajzovic, Lejla] Duke Univ, Eye Ctr, Durham, NC USA.
   [Freund, K. Bailey] NYU, Dept Ophthalmol, 550 1St Ave, New York, NY 10016 USA.
   [Walter, Scott D.] Univ Connecticut, Farmington, CT USA.
   [John, Vishak] Virginia Tech Carilion Sch Med, Vistar Eye Ctr, Roanoke, VA USA.
   [Rich, Ryan; Chittum, Mark] Retina Consultants Southern Colorado Pc, Colorado Springs, CO USA.
   [Chaudhry, Nauman] Yale Univ, Dept Ophthalmol, Sch Med, New Have, CT USA.
   [Lakhanpal, Rohit R.; Sund, Newman J.] Associated Retinal Consultants LLC, Retina Care Ctr LLC, Union, NJ USA.
   [Oellers, Patrick R.; Rutledge, Bryan K.] Retina Vitreous Surg Cent New York Pc, New York, NY USA.
   [Leveque, Thellea K.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA.
   [Subong, Eric N. P.] Retina Grp Seattle, Seattle, WA USA.
   [Albini, Thomas A.] Univ Miami, Leonard M Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL USA.
C3 Tufts University; Vitreous Retina Macula Consultants of New York; Duke
   University; New York University; University of Connecticut; Yale
   University; University of Washington; University of Washington Seattle;
   Bascom Palmer Eye Institute; University of Miami
RP Baumal, CR (通讯作者)，Tufts Med Ctr, New England Eye Ctr, 800 Washington St,Box 450, Boston, MA 02111 USA.
EM cbaumal@tuftsmedicalcenter.org
RI Bacci, Tommaso/GQA-8840-2022; Leveque, Thellea/AAC-3294-2019; Spaide,
   Richard/ABD-7368-2020; Freund, K. Bailey/V-7488-2018
OI Bacci, Tommaso/0000-0001-7477-2263; Walter, Scott/0000-0003-3492-4650;
   Freund, K. Bailey/0000-0002-7888-9773
FU Research to Prevent Blindness, Inc, New York, New York
FX Supported in part by Research to Prevent Blindness, Inc, New York, New
   York (challenge grant to the Department of Ophthalmology, Tufts Medical
   Center).
CR [Anonymous], 2018, INTRO GUIDE MEDRA VE
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NR 31
TC 102
Z9 104
U1 3
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD OCT
PY 2020
VL 127
IS 10
BP 1345
EP 1359
DI 10.1016/j.ophtha.2020.04.017
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA NT0HB
UT WOS:000572632200016
PM 32344075
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Daniel, S
   Renwick, M
   Chau, VQ
   Datta, S
   Maddineni, P
   Zode, G
   Wade, EM
   Robertson, SP
   Petroll, WM
   Hulleman, JD
AF Daniel, Steffi
   Renwick, Marian
   Chau, Viet Q.
   Datta, Shyamtanu
   Maddineni, Prabhavathi
   Zode, Gulab
   Wade, Emma M.
   Robertson, Stephen P.
   Petroll, W. Matthew
   Hulleman, John D.
TI Fibulin-3 knockout mice demonstrate corneal dysfunction but maintain
   normal retinal integrity
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE Fibulin-3; EFEMP1; Cornea; Retina; Malattia Leventinese (ML);
   Age-related macular degeneration (AMD)
ID ABERRANT ACCUMULATION; MALATTIA LEVENTINESE; MACULAR DEGENERATION; R345W
   FIBULIN-3; EFEMP1; MOUSE; MUTATION; DEPOSITS; DRUSEN; MODEL
AB Fibulin-3 (F3) is an extracellular matrix glycoprotein found in basement membranes across the body. An autosomal dominant R345W mutation in F3 causes a macular dystrophy resembling dry age-related macular degeneration (AMD), whereas genetic removal of wild-type (WT) F3 protects mice from sub-retinal pigment epithelium (RPE) deposit formation. These observations suggest that F3 is a protein which can regulate pathogenic sub-RPE deposit formation in the eye. Yet the precise role of WT F3 within the eye is still largely unknown. We found that F3 is expressed throughout the mouse eye (cornea, trabecular meshwork (TM) ring, neural retina, RPE/choroid, and optic nerve). We next performed a thorough structural and functional characterization of each of these tissues in WT and homozygous (F3(-/-)) knockout mice. The corneal stroma in F3(-/-)mice progressively thins beginning at 2 months, and the development of corneal opacity and vascularization starts at 9 months, which worsens with age. However, in all other tissues (TM, neural retina, RPE, and optic nerve), gross structural anatomy and functionality were similar across WT and F3(-/-)mice when evaluated using SD-OCT, histological analyses, electron microscopy, scotopic electroretinogram, optokinetic response, and axonal anterograde transport. The lack of noticeable retinal abnormalities in F3(-/-)mice was confirmed in a human patient with biallelic loss-of-function mutations in F3. These data suggest that (i) F3 is important for maintaining the structural integrity of the cornea, (ii) absence of F3 does not affect the structure or function of any other ocular tissue in which it is expressed, and (iii) targeted silencing of F3 in the retina and/or RPE will likely be well-tolerated, serving as a safe therapeutic strategy for reducing sub-RPE deposit formation in disease. Key messages center dot Fibulins are expressed throughout the body at varying levels. center dot Fibulin-3 has a tissue-specific pattern of expression within the eye. center dot Lack of fibulin-3 leads to structural deformities in the cornea. center dot The retina and RPE remain structurally and functionally healthy in the absence of fibulin-3 in both mice and humans.
C1 [Daniel, Steffi; Renwick, Marian; Chau, Viet Q.; Datta, Shyamtanu; Petroll, W. Matthew; Hulleman, John D.] Univ Texas Southwestern Med Ctr Dallas, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
   [Datta, Shyamtanu] Harvard Med Sch, Schepens Eye Res Inst, Dept Ophthalmol, Massachusetts Eye & Ear, Boston, MA 02115 USA.
   [Maddineni, Prabhavathi; Zode, Gulab] Univ North Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, 3500 Camp Bowie Blvd, Ft Worth, TX USA.
   [Wade, Emma M.; Robertson, Stephen P.] Univ Otago, Dunedin Sch Med, Dept Womens & Childrens Hlth, Dunedin 9016, New Zealand.
   [Hulleman, John D.] Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical
   Center Dallas; Harvard University; Harvard Medical School; Massachusetts
   Eye & Ear Infirmary; Schepens Eye Research Institute; University of
   North Texas System; University of North Texas Denton; University of
   North Texas Health Science Center; University of Otago; University of
   Texas System; University of Texas Southwestern Medical Center Dallas
RP Hulleman, JD (通讯作者)，Univ Texas Southwestern Med Ctr Dallas, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.; Hulleman, JD (通讯作者)，Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM John.Hulleman@UTSouthwestern.edu
RI Wade, Emma Mary/AAT-1035-2020
OI Hulleman, John/0000-0001-8149-656X; Petroll, W.
   Matthew/0000-0003-0795-4539; Maddineni, Prabhavathi/0000-0002-6928-254X;
   Wade, Emma M/0000-0003-2990-0232
FU UT Southwestern Summer Medical Student Research Program; Roger and
   Dorothy Hirl Research Fund; Karl Kirchgessner Foundation; BrightFocus
   Foundation [M2016200]; NEI [EY013322, EY027785, EY026177]; Research to
   Prevent Blindness (RPB); NEI Visual Science Core grant [P30 EY030413];
   RPB
FX VQC was supported by a funding from the UT Southwestern Summer Medical
   Student Research Program. JDH is supported by an endowment from the
   Roger and Dorothy Hirl Research Fund, a vision research grant from the
   Karl Kirchgessner Foundation, a BrightFocus Foundation Macular
   Degeneration Research Grant (M2016200), an NEI R01 grant (EY027785), and
   a Career Development Award from Research to Prevent Blindness (RPB).
   Additional support was provided by an NEI Visual Science Core grant (P30
   EY030413) and an unrestricted grant from RPB (both to the UT
   Southwestern Department of Ophthalmology). GZ is supported by an NEI R01
   grant (EY026177). WMP is supported by an NEI R01 grant (EY013322).
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   Zhang YW, 2010, EXP EYE RES, V90, P374, DOI 10.1016/j.exer.2009.09.018
   Zhivov A, 2009, BRIT J OPHTHALMOL, V93, P667, DOI 10.1136/bjo.2008.137430
NR 64
TC 3
Z9 3
U1 0
U2 1
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0946-2716
EI 1432-1440
J9 J MOL MED
JI J. Mol. Med.
PD NOV
PY 2020
VL 98
IS 11
BP 1639
EP 1656
DI 10.1007/s00109-020-01974-z
EA SEP 2020
PG 18
WC Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Research & Experimental Medicine
GA OK3MJ
UT WOS:000572008000001
PM 32964303
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Mekjavic, PJ
   Benda, PZ
AF Mekjavic, Polona Jaki
   Benda, Polona Zaletel
TI Outcome of 5-Year Treatment of Neovascular Age-Aelated Macular
   Degeneration With Intravitreal Anti-VEGF Using "Treat and Extend"
   Regimen
SO FRONTIERS IN MEDICINE
LA English
DT Article
DE treat and extend regimen; anti-VEGF agent; neovascular age-related
   macular degeneration; 5 years follow-up; long-term visual acuity outcome
ID TERM VISUAL OUTCOMES; CATARACT-SURGERY; RANIBIZUMAB; BLINDNESS;
   METAANALYSIS; EYES; RECOMMENDATIONS; PREVALENCE; TRIALS; BURDEN
AB Objective: The aim of this study is twofold. First, to evaluate the long-term outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment in a clinical setting using the "treat-and-extend regimen" (TER) in patients with neovascular age-related macular degeneration (nAMD). Second, to determine the proportion of patients treated with anti-VEGF with good visual acuity (VA), i.e., vision sufficient to maintain a high level of independence.
   Design: We conducted a single center retrospective review of patients with treatmentnaive nAMD who were treated with anti-VEGF. Patients were treated with anti-VEGF intravitreal injections according to the TER. Patients started treatment with monthly injections of either bevacizumab (1.25 mg/0.05 mL) or ranibizumab (0.5 mg/0.05 mL) until there were no signs present of choroidal neovascularization (CNV) activity. CNV activity was determined from fundus examination and SD-OCT imaging. Follow-up administration of intravitreal injections was extended by 2-week intervals, up to a total of 14 weeks, provided no signs of CNV activity were detected. In some patients, the first treatment was replaced with aflibercept (2 mg/0.05 mL).
   Participants: On the basis of the inclusion criterion for the study, that patients had to be treated for 5 years, a total of 101 patients were included in the study. In all patients, one eye was treated for a 5-year period, and thus we studied 101 eyes.
   Measurements: Best corrected VA was analyzed at baseline and each year during the 5-year follow-up.
   Results: VA improved initially after year 1 of the treatment. VA decreased in the subsequent 4 years of treatment, but remained significantly higher from year 1 to year 3 of the treatment compared to baseline values. Patients with good VA followed a similar trend: the proportion increased in the first year, and thereafter gradually decreased during the course of the 5-year follow up. At year 5, the number of patients with good VA decreased to baseline values.
   Conclusion: TER with anti-VEGF for nAMD treatment prevents long-term severe visual loss in real-world setting and maintains patients VA at levels sufficient to ensure independence.
C1 [Mekjavic, Polona Jaki; Benda, Polona Zaletel] Univ Med Ctr Ljubljana, Hosp Eye, Ljubljana, Slovenia.
   [Mekjavic, Polona Jaki] Univ Ljubljana, Fac Med, Ljubljana, Slovenia.
C3 University Medical Centre Ljubljana; University of Ljubljana
RP Mekjavic, PJ (通讯作者)，Univ Med Ctr Ljubljana, Hosp Eye, Ljubljana, Slovenia.; Mekjavic, PJ (通讯作者)，Univ Ljubljana, Fac Med, Ljubljana, Slovenia.
EM polona.jaki@guest.arnes.si
OI Zaletel Benda, Polona/0000-0003-3761-7349; Jaki Mekjavic,
   Polona/0000-0003-1949-4525
FU Slovene Research Agency
FX This work was supported, in part, by the Slovene Research Agency.
CR Ambati J, 2012, NEURON, V75, P26, DOI 10.1016/j.neuron.2012.06.018
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NR 32
TC 15
Z9 15
U1 0
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 2296-858X
J9 FRONT MED-LAUSANNE
JI Front. Med.
PD MAY 1
PY 2018
VL 5
AR 125
DI 10.3389/fmed.2018.00125
PG 9
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA GE5DH
UT WOS:000431238800001
PM 29765959
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Yazdanie, M
   Alvarez, J
   Agron, E
   Wong, WT
   Wiley, HE
   Ferris, FL
   Chew, EY
   Cukras, C
AF Yazdanie, Mohammad
   Alvarez, Jason
   Agron, Elvira
   Wong, Wai T.
   Wiley, Henry E.
   Ferris, Frederick L., III
   Chew, Emily Y.
   Cukras, Catherine
TI Decreased Visual Function Scores on a Low Luminance Questionnaire Is
   Associated with Impaired Dark Adaptation
SO OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIALS;
   MACULAR DEGENERATION; CONTRAST SENSITIVITY; CHOROIDAL
   NEOVASCULARIZATION; RETICULAR PSEUDODRUSEN; DESIGN; EYE; OUTCOMES
AB Purpose: We investigate whether responses on a Low Luminance Questionnaire (LLQ) in patients with a range of age-related macular degeneration (AMD) severity are associated with their performance on focal dark adaptation (DA) testing and with choroidal thickness.
   Design: Cross-sectional, single-center, observational study.
   Participants: A total of 113 participants older than 50 years of age with a range of AMD severity.
   Methods: Participants answered the LLQ on the same day they underwent DA testing using a focal dark adaptometer measuring rod intercept time (RIT). We performed univariable and multivariable analyses of the LLQ scores and age, RIT, AMD severity, subfoveal choroidal thickness [SFCT], phakic status, and best-corrected visual acuity.
   Main Outcome Measures: The primary outcome of this study was the score on the 32-question LLQ. Each item in the LLQ is designated to 1 of 6 subscales describing functional problems in low luminance: driving, emotional distress, mobility, extreme lighting, peripheral vision, and general dim lighting. Scores were computed for each subscale, in addition to a weighted total mean score.
   Results: Responses from 113 participants (mean age, 76.2 +/- 9.3 years; 58.4% were female) and 113 study eyes were analyzed. Univariable analysis demonstrated that lower scores on all LLQ subscales were correlated with prolonged DA testing (longer RIT) and decreased choroidal thickness. All associations were statistically significant except for the association of choroidal thickness and "peripheral vision." The strongest association was the LLQ subscale of driving with RIT (r =-0.97, P < 0.001). Multivariable analysis for each of the LLQ subscale outcomes, adjusted for age, included RIT, with total LLQ score, "driving," "extreme lighting," and "mobility" also including choroidal thickness. In all multivariable analyses, RIT had a stronger association than choroidal thickness.
   Conclusions: This cross-sectional analysis demonstrates associations of patient-reported functional deficits, as assessed on the LLQ, with both reduced DA and reduced choroidal thickness, in a population of older adults with varying degrees of AMD severity and good visual acuity in at least 1 eye. These analyses suggest that local functional measurements of DA testing (RIT) and choroidal thickness are associated with patient-reported functional deficits. Published by Elsevier on behalf of the American Academy of Ophthalmology
C1 [Yazdanie, Mohammad; Alvarez, Jason; Agron, Elvira; Wong, Wai T.; Wiley, Henry E.; Ferris, Frederick L., III; Chew, Emily Y.; Cukras, Catherine] NEI, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI)
RP Cukras, C (通讯作者)，NEI, NIH, Bethesda, MD 20892 USA.
EM cukrasc@nei.nih.gov
OI Ferris, Frederick/0000-0002-4933-0639
FU National Eye Institute Intramural Research Program, National Institutes
   of Health (NIH), Bethesda, Maryland; NIH Medical Research Scholars
   Program; NIH; NATIONAL EYE INSTITUTE [ZIAEY000509] Funding Source: NIH
   RePORTER
FX Supported by the National Eye Institute Intramural Research Program,
   National Institutes of Health (NIH), Bethesda, Maryland; and the NIH
   Medical Research Scholars Program, a public-private partnership
   supported jointly by the NIH, and generous contributions to the
   Foundation for the NIH from Pfizer, Inc., The Doris Duke Charitable
   Foundation, The Alexandria Real Estate Equities, Inc., Mr. and Mrs. Joel
   S. Marcus, the Howard Hughes Medical Institute, as well as other private
   donors.
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NR 49
TC 20
Z9 20
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD SEP
PY 2017
VL 124
IS 9
BP 1332
EP 1339
DI 10.1016/j.ophtha.2017.05.005
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FD8RT
UT WOS:000407792500017
PM 28602520
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Brown, GC
   Brown, MM
   Lieske, HB
   Lieske, PA
   Brown, KS
   Lane, SS
AF Brown, Gary C.
   Brown, Melissa M.
   Lieske, Heidi B.
   Lieske, Philip A.
   Brown, Kathryn S.
   Lane, Stephen S.
TI Comparative Effectiveness and Cost-Effectiveness of the Implantable
   Miniature Telescope
SO OPHTHALMOLOGY
LA English
DT Article
ID VALUE-BASED MEDICINE; VISUAL-ACUITY LOSS; QUALITY-OF-LIFE; MACULAR
   DEGENERATION; UTILITY VALUES; RANIBIZUMAB; INTERVENTIONS
AB Objective: To assess the preference-based comparative effectiveness (human value gain) and the costutility (cost-effectiveness) of a telescope prosthesis (implantable miniature telescope) for the treatment of end-stage, age-related macular degeneration (AMD).
   Design: A value-based medicine, second-eye model, cost-utility analysis was performed to quantify the comparative effectiveness and cost-effectiveness of therapy with the telescope prosthesis.
   Participants: Published, evidence-based data from the IMT002 Study Group clinical trial. Ophthalmic utilities were obtained from a validated cohort of >1000 patients with ocular diseases.
   Methods: Comparative effectiveness data were converted from visual acuity to utility (value-based) format. The incremental costs (Medicare) of therapy versus no therapy were integrated with the value gain conferred by the telescope prosthesis to assess its average cost-utility. The incremental value gains and incremental costs of therapy referent to (1) a fellow eye cohort and (2) a fellow eye cohort of those who underwent intra-study cataract surgery were integrated in incremental cost-utility analyses. All value outcomes and costs were discounted at a 3% annual rate, as per the Panel on Cost-Effectiveness in Health and Medicine.
   Main Outcome Measures: Comparative effectiveness was quantified using the (1) quality-adjusted life-year (QALY) gain and (2) percent human value gain (improvement in quality of life). The QALY gain was integrated with incremental costs into the cost-utility ratio ($/QALY, or US dollars expended per QALY gained).
   Results: The mean, discounted QALY gain associated with use of the telescope prosthesis over 12 years was 0.7577. When the QALY loss of 0.0004 attributable to the adverse events was factored into the model, the final QALY gain was 0.7573. This resulted in a 12.5% quality of life gain for the average patient during the 12 years of the model. The average cost-utility versus no therapy for use of the telescope prosthesis was $14 389/QALY. The incremental cost-utility referent to control fellow eyes was $14 063/QALY, whereas the incremental costutility referent to fellow eyes that underwent intra-study cataract surgery was $11 805/QALY.
   Conclusions: Therapy with the telescope prosthesis considerably improves quality of life and at the same time is cost-effective by conventional standards.
C1 [Brown, Gary C.; Brown, Melissa M.; Lieske, Heidi B.; Lieske, Philip A.; Brown, Kathryn S.] Ctr Value Based Med, Flourtown, PA 19031 USA.
   [Brown, Gary C.; Brown, Melissa M.] Eye Res Inst, Philadelphia, PA USA.
   [Brown, Gary C.] Thomas Jefferson Univ, Jefferson Med Coll, Retina Serv, Wills Eye Inst, Philadelphia, PA 19107 USA.
   [Brown, Melissa M.] Thomas Jefferson Univ, Jefferson Med Coll, Res Dept, Wills Eye Inst, Philadelphia, PA 19107 USA.
   [Brown, Melissa M.] Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Lane, Stephen S.] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA.
C3 Jefferson University; Jefferson University; University of Pennsylvania;
   University of Minnesota System; University of Minnesota Twin Cities
RP Brown, GC (通讯作者)，Ctr Value Based Med, Box 335, Flourtown, PA 19031 USA.
EM gary0514@gmail.com
FU VisionCare Ophthalmic Technologies; Center for Value-Based Medicine,
   Flourtown, Pennsylvania
FX Supported in part by grants from VisionCare Ophthalmic Technologies and
   the Center for Value-Based Medicine, Flourtown, Pennsylvania. The
   sponsors played no role in performance of the study, writing of the
   manuscript, or direction of the study.
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   *SOC SEC, 2006, ACT PUBL SOC SEC
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   *VISIONCARE OPHTH, 2010, PAT INF BOOKL, P20
   World Health Organization, 2002, WORLD HLTH REP 2002, P108
   ASC CAMPAIGN ADV SUR
NR 47
TC 17
Z9 17
U1 0
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD SEP
PY 2011
VL 118
IS 9
BP 1834
EP 1843
DI 10.1016/j.ophtha.2011.02.012
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 814TD
UT WOS:000294479200021
PM 21723614
DA 2022-11-30
ER

PT J
AU Wielgus, AR
   Collier, RJ
   Martin, E
   Lih, FB
   Tomer, KB
   Chignell, CF
   Roberts, JE
AF Wielgus, A. R.
   Collier, R. J.
   Martin, E.
   Lih, F. B.
   Tomer, K. B.
   Chignell, C. F.
   Roberts, J. E.
TI Blue light induced A2E oxidation in rat eyes - experimental animal model
   of dry AMD
SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
LA English
DT Article
ID AGE-RELATED MACULOPATHY; PIGMENT EPITHELIAL-CELLS; SINGLET-OXYGEN
   GENERATION; MACULAR DEGENERATION; LIPOFUSCIN FLUOROPHORE; BRUCHS
   MEMBRANE; AGING RETINA; DAMAGE; RPE; ACCUMULATION
AB Previous studies have shown that short-wavelength blue visible light induces retinal injury and may be a risk factor for age related macular degeneration. A2E is a blue light absorbing retinal chromophore that accumulates with age. Our previous in vitro studies have determined that, although A2E itself has a low phototoxic efficiency, the oxidation products of A2E that are formed in the presence of visible light can contribute to observed retinal pigment epithelial photodamage. The purpose of this study was to investigate the effects of blue light on retinal phototoxicity and its relationship to A2E, oxidized A2E and its isomers. Sprague-Dawley albino rats were dark adapted for 24 h. Control rats remained in the dark while experimental rats were exposed to blue light (lambda = 450 nm, 3.1 mW cm(-2)) for 6 h. Isolated retinas were homogenized in Folch extraction mixture and then in chloroform. The dried extracts were reconstituted and divided for determination of organic soluble compound. Esters of fatty acids were determined with GC-MS, A2E and other chromophores using HPLC, and A2E oxidation products with LC-MS. Exposure of rat eyes to blue light did not significantly change the fatty acid composition of the retina. The A2E concentration (normalized to fatty acid content) in blue light exposed animals was found to be lower than the A2E concentration in control rats. The concentrations of all-trans-retinal-ethanolamine adduct and iso-A2E a precursor and an isomer of A2E respectively, were also lower after blue-light exposure than in the retinas of rats housed in the dark. On the other hand, the amount of oxidized forms of A2E was higher in the animals exposed to blue light. We conclude that in the rat eye, blue-light exposure promotes oxidation of A2E and iso-A2E to the products that are toxic to retinal tissue. Although high concentrations of A2E may be cytotoxic to the retina, the phototoxicity associated with blue light damage to the retina is in part a result of the formation of toxic A2E oxides. This effect may partially explain the association between blue light induced retinal injury and macular degeneration.
C1 [Wielgus, A. R.; Chignell, C. F.] Natl Inst Environm Hlth Sci, Pharmacol Lab, Res Triangle Pk, NC 27709 USA.
   [Collier, R. J.; Martin, E.] Alcon Res Ltd, Retinopathy Degenerat Dis Res Unit, Ft Worth, TX 76134 USA.
   [Lih, F. B.; Tomer, K. B.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
   [Roberts, J. E.] Fordham Univ, Dept Nat Sci, New York, NY 10023 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of
   Environmental Health Sciences (NIEHS); Novartis; Alcon; National
   Institutes of Health (NIH) - USA; NIH National Institute of
   Environmental Health Sciences (NIEHS); Fordham University
RP Wielgus, AR (通讯作者)，Natl Inst Environm Hlth Sci, Pharmacol Lab, Res Triangle Pk, NC 27709 USA.
EM albert.wielgus@duke.edu; jroberts@fordham.edu
RI Tomer, Kenneth B/E-8018-2013
FU NIH, National Institute of Environmental Health Sciences [Z01 ES050167];
   Alcon Research Grant; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH
   SCIENCES [ZIAES050167] Funding Source: NIH RePORTER
FX This research was supported by the Intramural Research Program of the
   NIH, National Institute of Environmental Health Sciences (ARW), Z01
   ES050167 (KBT) and partially by an Alcon Research Grant (JER).
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NR 72
TC 72
Z9 84
U1 0
U2 22
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 1474-905X
EI 1474-9092
J9 PHOTOCH PHOTOBIO SCI
JI Photochem. Photobiol. Sci.
PY 2010
VL 9
IS 11
BP 1505
EP 1512
DI 10.1039/c0pp00133c
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics; Chemistry
GA 672QX
UT WOS:000283603100012
PM 20922251
DA 2022-11-30
ER

PT J
AU Wang, S
   Xu, L
   Jonas, JB
   Wong, TY
   Cui, TT
   Li, YB
   Wang, YX
   You, QS
   Yang, H
   Sun, C
AF Wang, Shuang
   Xu, Liang
   Jonas, Jost B.
   Wong, Tien Y.
   Cui, Tongtong
   Li, Yibin
   Wang, Ya Xing
   You, Qi Sheng
   Yang, Hua
   Sun, Cong
TI Major Eye Diseases and Risk Factors Associated with Systemic
   Hypertension in an Adult Chinese Population The Beijing Eye Study
SO OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; RETINAL VASCULAR CALIBER; BLOOD-PRESSURE;
   INTRAOCULAR-PRESSURE; ATHEROSCLEROSIS RISK; VEIN OCCLUSION;
   LAMINA-CRIBROSA; PREVALENCE; ARTERIOLAR; URBAN
AB Purpose: To assess the relationship of hypertension with major eye diseases and other ocular parameters.
   Design: Population-based study.
   Participants: The Beijing Eye Study is a population-based study that included 4439 Chinese subjects examined at the baseline examination in 2001; there was a follow-up examination in 2006, in which 3251 subjects participated, of whom 3222 had blood pressure measurements.
   Methods: All participants underwent an ophthalmic examination, anthropometric measurements, and blood pressure measurement. Hypertension was defined as a systolic blood pressure >= 140 mmHg and/or diastolic blood pressure 90 mmHg, and/or self-reported current treatment for hypertension with anti hypertensive medication.
   Main Outcome Measures: Blood pressure and ocular parameters, including intraocular pressure and prevalence of major ophthalmic diseases.
   Results: Mean age of participants in the present study was 60.4 +/- 10.0 years. Hypertension was present in 1500 (46.6%) of the 3222 subjects who had their blood pressure measured. In multiple regression analysis, hypertension was associated with higher intraocular pressure (beta = 0.39; 95% confidence interval [CI], 0.12-0.66; P = 0.005), focal arteriolar narrowing (odds ratio [OR], 1.78; 95% CI, 1.34-2.36; P<0.001), arteriovenous nicking (OR, 1.50; 95% CI, 1.11-2.04; P = 0.009), generalized retinal arteriolar narrowing (OR, 1.65; 95% CI, 1.30-2.09; P<0.001), retinal vein occlusions (OR, 2.86; 95% CI, 1.21-6.80; P = 0.02), and diabetic retinopathy (OR, 1.90; 95% CI, 1.08-3.31; P = 0.02). Hypertension was not significantly associated with the prevalence of open-angle glaucoma (P = 0.19), angle-closure glaucoma (P = 0.15), age-related macular degeneration (AMD) (P = 0.73), nuclear cataract (P = 0.88), posterior subcapsular cataract (P = 0.30), cortical cataract (P = 0.10), or area of alpha zone (P = 0.05) or beta zone of parapapillary atrophy (P = 0.95).
   Conclusions: In Chinese persons, while controlling for other systemic parameters, hypertension was associated with increased intraocular pressure, retinal microvascular abnormalities, and prevalence of retinal vein occlusion and diabetic retinopathy. Hypertension was not associated significantly with AMD, age-related cataract, or glaucoma.
C1 [Wang, Shuang; Xu, Liang; Jonas, Jost B.; Cui, Tongtong; Li, Yibin; Wang, Ya Xing; You, Qi Sheng; Yang, Hua] Capital Univ Med Sci, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing 100005, Peoples R China.
   [Jonas, Jost B.] Heidelberg Univ, Fac Clin Med Mannheim, Dept Ophthalmol, D-6800 Mannheim, Germany.
   [Wong, Tien Y.; Sun, Cong] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.
   [Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117595, Singapore.
C3 Capital Medical University; Ruprecht Karls University Heidelberg; Centre
   for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; National University of Singapore; Singapore
   National Eye Center
RP Xu, L (通讯作者)，Capital Univ Med Sci, Beijing Tongren Hosp, Beijing Inst Ophthalmol, 17 Hougou St, Beijing 100005, Peoples R China.
EM twong@unimelb.edu.au; twong@unimelb.edu.au
RI You, Qisheng/AAG-7153-2020; wang, YA XING/K-9671-2016; You,
   Qisheng/A-3619-2014; Wong, Tien Yin/AAC-9724-2020
OI You, Qisheng/0000-0003-0743-7320; wang, YA XING/0000-0003-2749-7793;
   You, Qisheng/0000-0003-0743-7320; Wong, Tien Yin/0000-0002-8448-1264
FU Beijing Municipal Natural Science Foundation; Bureau of International
   Cooperation; Beijing Municipal Science and Technology Commission
FX Supported by Beijing Municipal Natural Science Foundation and Bureau of
   International Cooperation, Beijing Municipal Science and Technology
   Commission.
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NR 50
TC 61
Z9 65
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD DEC
PY 2009
VL 116
IS 12
BP 2373
EP 2380
DI 10.1016/j.ophtha.2009.05.041
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 530HE
UT WOS:000272579200017
PM 19815279
DA 2022-11-30
ER

PT J
AU Xu, L
   You, QS
   Jonas, JB
AF Xu, Liang
   You, Qi Sheng
   Jonas, Jost B.
TI Prevalence of Alcohol Consumption and Risk of Ocular Diseases in a
   General Population. The Beijing Eye Study
SO OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; HIGH-DENSITY-LIPOPROTEIN; MACULAR DEGENERATION;
   5-YEAR INCIDENCE; SMOKING; ASSOCIATION; DRINKING; GLAUCOMA; CHINESE;
   LIGHT
AB Objective: To examine the associations between alcohol consumption and ocular diseases in the adult population of mainland China.
   Design: Population-based study.
   Participants: The Beijing Eye Study, performed in 2001, included 4439 subjects (age 40 + years) of 5324 individuals invited to participate (response rate 83.4%). The study was conducted in both a rural region (1973 subjects) and an urban region of Greater Beijing (2466 subjects).
   Methods: All participants underwent an interview, including questions about alcohol consumption and a detailed ophthalmic examination, including photography of the cornea, lens, and fundus.
   Main Outcome Measures: Consumption of alcohol and systemic and ophthalmic parameters.
   Results: Information on alcohol consumption was obtained on 4141 subjects (93.3%), of whom 549 (13.3%) reported they consumed beer or wine. In multivariate analysis, alcohol consumption was significantly associated with the systemic parameters of lower age (P = 0.001), male gender (P<0.001), rural region (P<0.001), lower level of education (P = 0.01), and smoking (P<0.001). Alcohol consumption was not a significant risk factor for the prevalences of age-related macular degeneration (P = 0.24), open-angle glaucoma (P = 0.51), angle-closure glaucoma (P = 0.75), diabetic retinopathy (P = 0.35), retinal vein occlusion (P = 0.39), pterygium (P = 0.08), trachoma (P = 0.053), epiretinal membrane (P = 0.09), non-glaucomatous optic nerve atrophy (P = 0.55), dry eye (P = 0.86), cortical cataract (P = 0.67), subcapsular posterior cataract (P = 0.62), or nuclear cataract (P = 0.76), or with the ocular parameters of refractive error (P = 0.99), intraocular pressure (P = 0.19), retinal artery diameters (temporal inferior: P = 0.60), retinal vein diameters (temporal inferior: P = 0.41), or size of alpha zone and beta zone of parapapillary atrophy (P = 0.68).
   Conclusions: When adjusted for the systemic parameters of age, gender, rural/urban region, level of education, and smoking, self-reported moderate consumption of alcohol does not have a significant effect on the prevalence of major ocular diseases or the physiologic parameters of intraocular pressure and refractive error.
   Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:1872-1879 (C) 2009 by the American Academy of Ophthalmology.
C1 [Xu, Liang; You, Qi Sheng; Jonas, Jost B.] Capital Med Univ, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing 100005, Peoples R China.
   [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, D-6900 Heidelberg, Germany.
C3 Capital Medical University; Ruprecht Karls University Heidelberg
RP Xu, L (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Beijing Inst Ophthalmol, 17 Hougou St, Beijing 100005, Peoples R China.
EM xlbio@yahoo.cn
RI You, Qisheng/A-3619-2014; You, Qisheng/AAG-7153-2020
OI You, Qisheng/0000-0003-0743-7320; You, Qisheng/0000-0003-0743-7320
FU Beijing Key Laboratory Funding, Beijing, China
FX Funding: Beijing Key Laboratory Funding, Beijing, China.
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NR 48
TC 40
Z9 41
U1 0
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD OCT
PY 2009
VL 116
IS 10
BP 1872
EP 1879
DI 10.1016/j.ophtha.2009.04.014
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 506RX
UT WOS:000270794600007
PM 19712977
DA 2022-11-30
ER

PT J
AU Yi, CJ
   Liu, J
   Deng, W
   Luo, C
   Qi, JY
   Chen, M
   Xu, HP
AF Yi, Caijiao
   Liu, Jian
   Deng, Wen
   Luo, Chang
   Qi, Jinyan
   Chen, Mei
   Xu, Heping
TI Macrophage elastase (MMP12) critically contributes to the development of
   subretinal fibrosis
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Age-related macular degeneration; Macular fibrosis; Inflammation; Matrix
   metalloproteinase-12; RNA sequencing
ID METALLOELASTASE MMP-12; MATRIX; PROTEINS; LEVEL; EYES
AB Background Macular subretinal fibrosis is the end-stage complication of neovascular age-related macular degeneration (nAMD). We previously developed a mouse model of two-stage laser-induced subretinal fibrosis that mimics closely the dynamic course of macular fibrosis in nAMD patients. This study was aimed to understand the molecular mechanism of subretinal fibrosis. Methods Subretinal fibrosis was induced in C57BL/6J mice using the two-stage laser-induced protocol. Twenty days later, eyes were collected and processed for RNA sequencing (RNA-seq) analysis. DESeq2 was used to determine the differentially expressed genes (DEGs). Gene Ontology (GO) and KEGG were used to analyze the enriched pathways. The expression of the selected DEGs including Mmp12 was verified by qPCR. The expression of MMP12 in subretinal fibrosis of mouse and nAMD donor eyes was examined by immunofluorescence and confocal microscopy. The expression of collagen 1, alpha SMA and fibronectin and cytokines in bone marrow-derived macrophages from control and subretinal fibrosis mice were examined by qPCR, immunocytochemistry and Luminex multiplex cytokine assay. The MMP12 specific inhibitor MMP408 was used to evaluate the effect of MMP12 on TGF beta-induced macrophage-to-myofibroblast transition (MMT) in vitro and its role in subretinal fibrosis in vivo. Results RNA-seq analysis of RPE-choroid from subretinal fibrosis eyes uncovered 139 DEGs (fold change log2(fc) >= 0.5, FDR < 0.05), including 104 up-regulated and 35 were down-regulated genes. The top 25 enrichment GO terms were related to inflammation, blood vessels/cardiovascular development and angiogenesis. One of the most significantly upregulated genes, Mmp12, contributed to 12 of the top 25 GO terms. Higher levels of MMP12 were detected in subretinal fibrotic lesions in nAMD patients and the mouse model, including in F4/80(+) or Iba1(+) macrophages. BMDMs from subretinal fibrosis mice expressed higher levels of MMP12, collagen-1, alpha SMA and fibronectin. MMP408 dose-dependently suppressed TGF beta-induced MMT in BMDMs. In vivo treatment with MMP408 (5 mg/kg) significantly reduced subretinal fibrosis accompanied by reduced F4/80(+) macrophage infiltration. Conclusions MMP12 critically contributes to the development of subretinal fibrosis, partially through promoting MMT.
C1 [Yi, Caijiao; Deng, Wen; Luo, Chang; Qi, Jinyan; Chen, Mei; Xu, Heping] Cent South Univ, Aier Sch Ophthalmol, Changsha 410000, Peoples R China.
   [Liu, Jian; Xu, Heping] Aier Inst Optometry & Vis Sci, Changsha 410000, Peoples R China.
   [Xu, Heping] Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, Sch Med Dent & Biomed Sci, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
C3 Central South University; Queens University Belfast
RP Xu, HP (通讯作者)，Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, Sch Med Dent & Biomed Sci, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
EM heping.xu@qub.ac.uk
OI Xu, Heping/0000-0003-4000-931X
FU Hunan Science & Technology Association [2021KX001]; Science & Technology
   Department of Hunan Province [2018RS3123]; Hunan Provincial Natural
   Science Youth Fund [2021JJ4002]; Science Research Foundation of Aier Eye
   Hospital Group [AM1913D1, AR2003D1]; Fight for Sight [5057/5058,
   5105/5106]
FX This study was funded by Hunan Science & Technology Association
   (2021KX001), and Science & Technology Department of Hunan Province
   (2018RS3123), Hunan Provincial Natural Science Youth Fund (2021JJ4002),
   Science Research Foundation of Aier Eye Hospital Group (AM1913D1,
   AR2003D1), and Fight for Sight (5057/5058, 5105/5106).
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NR 42
TC 0
Z9 0
U1 1
U2 2
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD APR 5
PY 2022
VL 19
IS 1
AR 78
DI 10.1186/s12974-022-02433-x
PG 16
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA 0H6HU
UT WOS:000778834000002
PM 35382832
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Takahashi, K
   Nakamura, S
   Otsu, W
   Shimazawa, M
   Hara, H
AF Takahashi, Kei
   Nakamura, Shinsuke
   Otsu, Wataru
   Shimazawa, Masamitsu
   Hara, Hideaki
TI Progranulin deficiency in Iba-1(+) myeloid cells exacerbates choroidal
   neovascularization by perturbation of lysosomal function and abnormal
   inflammation
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Progranulin; Microglia; Macrophage; Lysosome; Inflammation;
   Neovascularization
ID MACULAR DEGENERATION; VEGF EXPRESSION; MICROGLIA; ACCUMULATION;
   FEATURES; PHENOTYPE; HYPOXIA; PROTEIN; FAMILY; INJURY
AB Background Age-related macular degeneration (AMD) is the principal cause of permanent blindness among elderly individuals worldwide. Chronic inflammation in the subretinal space is associated with a progression of exudative AMD. Progranulin (PGRN) is a growth factor secreted from myeloid cells and plays an important role in controlling the lysosomal function. A deficiency in PGRN leads to inflammation of the neurons in the central nervous system. The purpose of this study was to investigate the role played by PGRN in the size of the choroidal neovascularization (CNV) in laser-induced CNV mice. Methods CNVs were induced in C57BL/6J mice by laser photocoagulation of the retina. The expression of PGRN and the accumulation of Iba-1(+) cells around the sites of the CNVs were determined. Grn(-/-), Grn(+/-), and Grn(+/+) mice with laser-induced CNVs were also studied. To evaluate the effect of macrophages on the inflammation, we used a macrophage cell line (RAW264.7) in which the expression of PGRN was knocked down by RNA interference and peritoneal macrophages derived from Grn(-/-) and Grn(+/+) mice. These cells were incubated under hypoxic conditions (1% O-2). Results Iba-1(+) myeloid cells migrated and accumulated in the photocoagulation-induced CNV areas, and the CNV lesions secreted high levels of PGRN in Grn(+/+) mice. The size of the CNVs was larger in Grn(-/-) mice than in Grn(+/-) and Grn(+/+) mice. In Grn(-/-) mice, the number of ocular-infiltrating Iba-1(+) cells around the CNV was higher, and these cells produced more VEGF-A than the cells in the Grn(+/+) mice. PGRN-silencing of RAW264.7 cells led to abnormal activation of the cells. In addition, hypoxic conditions promoted the production of proangiogenic and proinflammatory cytokines from PGRN-deficient macrophages. Interestingly, the expression level of lysosome-associated proteins and the number of activated lysosomes increased in PGRN-deficient macrophages. Conclusions These findings indicate that PGRN deficiency in Iba-1(+) cells activates the lysosomal function that then leads to abnormal inflammation. The aberrant activation of Iba-1(+) myeloid cells might contribute to the progression of the CNV and the regulation of these cells might be a novel therapeutic target for exudative AMD.
C1 [Takahashi, Kei; Nakamura, Shinsuke; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
   [Otsu, Wataru; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biomed Res Lab, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
C3 Gifu Pharmaceutical University; Gifu Pharmaceutical University
RP Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.; Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biomed Res Lab, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
EM hidehara@gifu-pu.ac.jp
OI Hara, Hideaki/0000-0003-2046-9001; Takahashi, Kei/0000-0002-7455-0465
FU Nagai Memorial Research Scholarship from the Pharmaceutical Society of
   Japan
FX This study was supported by grants from the Nagai Memorial Research
   Scholarship from the Pharmaceutical Society of Japan.
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   Xu NN, 2019, INVEST OPHTH VIS SCI, V60, P4596, DOI 10.1167/iovs.19-27493
   Youn BS, 2009, DIABETES, V58, P627, DOI 10.2337/db08-1147
   Yu C, 2020, TRENDS NEUROSCI, V43, P433, DOI 10.1016/j.tins.2020.03.012
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NR 50
TC 3
Z9 3
U1 1
U2 1
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD JUL 25
PY 2021
VL 18
IS 1
AR 164
DI 10.1186/s12974-021-02203-1
PG 16
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA TP6KS
UT WOS:000677707100001
PM 34304733
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Cheng, KC
   Hsu, YT
   Liu, WT
   Huang, HL
   Chen, LY
   He, CX
   Sheu, SJ
   Chen, KJ
   Lee, PY
   Lin, YH
   Chiu, CC
AF Cheng, Kai-Chun
   Hsu, Yun-Tzu
   Liu, Wangta
   Huang, Huey-Lan
   Chen, Liang-Yu
   He, Chen-Xi
   Sheu, Shwu-Jiuan
   Chen, Kuo-Jen
   Lee, Po-Yen
   Lin, Yi-Hsiung
   Chiu, Chien-Chih
TI The Role of Oxidative Stress and Autophagy in Blue-Light-Induced Damage
   to the Retinal Pigment Epithelium in Zebrafish In Vitro and In Vivo
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE retinal pigment epithelium; blue light; DNA damage; apoptosis; reactive
   oxygen species; autophagy; zebrafish-model; degeneration
ID INDUCED APOPTOSIS; CELLS; DEATH; DEGENERATION; EXPRESSION; PROTECTS
AB Age-related macular degeneration (AMD) is the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris among elderly individuals and is the leading cause of blindness worldwide. Thus, a better understanding of the underlying mechanisms in retinal tissue activated by blue light exposure is important for developing novel treatment and intervention strategies. In this study, blue-light-emitting diodes with a wavelength of 440 nm were applied to RPE cells at a dose of 3.7 +/- 0.75 mW/cm(2) for 24 h. ARPE-19 cells were used to investigate the underlying mechanism induced by blue light exposure. A trypan blue exclusion assay was used for the cell viability determination. Flow cytometry was used for apoptosis rate detection and autophagy analysis. An immunofluorescence microscopy analysis was used to investigate cellular oxidative stress and DNA damage using DCFDA fluorescence staining and an anti-gamma H2AX antibody. Blue light exposure of zebrafish larvae was established to investigate the effect on retinal tissue development in vivo. To further demonstrate the comprehensive effect of blue light on ARPE-19 cells, next-generation sequencing (NGS) was performed for an ingenuity pathway analysis (IPA) to reveal additional related mechanisms. The results showed that blue light exposure caused a decrease in cell proliferation and an increase in apoptosis in ARPE-19 cells in a time-dependent manner. Oxidative stress increased during the early stage of 2 h of exposure and activated DNA damage in ARPE-19 cells after 8 h. Furthermore, autophagy was activated in response to blue light exposure at 24-48 h. The zebrafish larvae model showed the unfavorable effect of blue light in prohibiting retinal tissue development. The RNA-Seq results confirmed that blue light induced cell death and participated in tissue growth inhibition and maturation. The current study reveals the mechanisms by which blue light induces cell death in a time-dependent manner. Moreover, both the in vivo and NGS data uncovered blue light's effect on retinal tissue development, suggesting that exposing children to blue light could be relatively dangerous. These results could benefit the development of preventive strategies utilizing herbal medicine-based treatments for eye diseases or degeneration in the future.
C1 [Cheng, Kai-Chun; Chen, Kuo-Jen] Kaohsiung Municipal Siaogang Hosp, Dept Ophthalmol, Kaohsiung 812, Taiwan.
   [Cheng, Kai-Chun; Sheu, Shwu-Jiuan; Lee, Po-Yen] Kaohsiung Med Univ Hosp, Dept Ophthalmol, Kaohsiung 807, Taiwan.
   [Cheng, Kai-Chun; Sheu, Shwu-Jiuan] Kaohsiung Med Univ, Sch Med, Dept Ophthalmol, Coll Med, Kaohsiung 807, Taiwan.
   [Hsu, Yun-Tzu; Liu, Wangta; He, Chen-Xi; Lin, Yi-Hsiung; Chiu, Chien-Chih] Kaohsiung Med Univ, Dept Biotechnol, Kaohsiung 807, Taiwan.
   [Liu, Wangta; Chiu, Chien-Chih] Kaohsiung Med Univ, Ctr Canc Res, Kaohsiung 807, Taiwan.
   [Liu, Wangta; Chiu, Chien-Chih] Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung 807, Taiwan.
   [Huang, Huey-Lan] Chang Jung Christian Univ, Dept Biosci Technol, Coll Hlth Sci, Tainan 711, Taiwan.
   [Chen, Liang-Yu] Kaohsiung Med Univ, Dept Med, Kaohsiung 807, Taiwan.
   [Lin, Yi-Hsiung] Kaohsiung Med Univ Hosp, Div Cardiol, Dept Internal Med, Kaohsiung 807, Taiwan.
   [Lin, Yi-Hsiung] Kaohsiung Med Univ Hosp, Ctr Lipid Biosci, Kaohsiung 807, Taiwan.
   [Lin, Yi-Hsiung] Kaohsiung Med Univ, Lipid Sci & Aging Res Ctr, Kaohsiung 807, Taiwan.
   [Chiu, Chien-Chih] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung 804, Taiwan.
   [Chiu, Chien-Chih] Kaohsiung Med Univ, Grad Inst Med, Kaohsiung 807, Taiwan.
C3 Kaohsiung Medical University; Kaohsiung Municipal Siao-Gang Hospital;
   Kaohsiung Medical University; Kaohsiung Medical University Hospital;
   Kaohsiung Medical University; Kaohsiung Medical University; Kaohsiung
   Medical University; Kaohsiung Medical University; Kaohsiung Medical
   University Hospital; Chang Jung Christian University; Kaohsiung Medical
   University; Kaohsiung Medical University; Kaohsiung Medical University
   Hospital; Kaohsiung Medical University; Kaohsiung Medical University
   Hospital; Kaohsiung Medical University; National Sun Yat Sen University;
   Kaohsiung Medical University
RP Lin, YH; Chiu, CC (通讯作者)，Kaohsiung Med Univ, Dept Biotechnol, Kaohsiung 807, Taiwan.; Chiu, CC (通讯作者)，Kaohsiung Med Univ, Ctr Canc Res, Kaohsiung 807, Taiwan.; Chiu, CC (通讯作者)，Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung 807, Taiwan.; Lin, YH (通讯作者)，Kaohsiung Med Univ Hosp, Div Cardiol, Dept Internal Med, Kaohsiung 807, Taiwan.; Lin, YH (通讯作者)，Kaohsiung Med Univ Hosp, Ctr Lipid Biosci, Kaohsiung 807, Taiwan.; Lin, YH (通讯作者)，Kaohsiung Med Univ, Lipid Sci & Aging Res Ctr, Kaohsiung 807, Taiwan.; Chiu, CC (通讯作者)，Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung 804, Taiwan.; Chiu, CC (通讯作者)，Kaohsiung Med Univ, Grad Inst Med, Kaohsiung 807, Taiwan.
EM pington64@gmail.com; tzu0611@gmail.com; liuwangta@kmu.edu.tw;
   hhuang@mail.cjcu.edu.tw; verity0418@gmail.com; u106500025@kmu.edu.tw;
   sjiuansheu@gmail.com; 0870649@kmhk.org.tw; maco69@gmail.com;
   tzu0611@gmail.com; cchiu@kmu.edu.tw
RI Chiu, Chien-Chih/AAW-9861-2020
OI Chiu, Chien-Chih/0000-0001-7307-2468; Lee, Po Yen/0000-0002-1825-0003;
   Cheng, Kai-Chun/0000-0002-1240-4219
FU Ministry of Science and Technology, Taiwan [MOST 108-2314-B-037-088,
   108-2314-B-037-051]; Kaohsiung Municipal Siaogang Hospital, Taiwan
   [KMHK-106-022, KMHK-107-008, KMHK-108-032]
FX The research was supported by grants MOST 108-2314-B-037-088 and
   108-2314-B-037-051 from the Ministry of Science and Technology, Taiwan,
   and grants KMHK-106-022, KMHK-107-008 and KMHK-108-032 from Kaohsiung
   Municipal Siaogang Hospital, Taiwan. We are also grateful to the Center
   for Research Resources and Development (Kaohsiung Medical University)
   for their instrumental support with IPA, flow cytometry, and confocal
   microscopy.
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NR 29
TC 8
Z9 8
U1 4
U2 18
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD FEB
PY 2021
VL 22
IS 3
AR 1338
DI 10.3390/ijms22031338
PG 17
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA QD3FT
UT WOS:000615409300001
PM 33572787
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Zangwill, LM
   Ayyagari, R
   Liebmann, JM
   Girkin, CA
   Feldman, R
   Dubiner, H
   Dirkes, KA
   Holmann, M
   Williams-Steppe, E
   Hammel, N
   Saunders, LJ
   Vega, S
   Sandow, K
   Roll, K
   Slight, R
   Auerbach, D
   Samuels, BC
   Panarelli, JF
   Mitchell, JP
   Al-Aswad, LA
   Park, SC
   Tello, C
   Cotliar, J
   Bansal, R
   Sidoti, PA
   Cioffi, GA
   Blumberg, D
   Ritch, R
   Bell, NP
   Blieden, LS
   Davis, G
   Medeiros, FA
   Ng, MCY
   Das, SK
   Palmer, ND
   Divers, J
   Langefeld, CD
   Freedman, BI
   Bowden, DW
   Christopher, MA
   Chen, YDI
   Guo, XQ
   Taylor, KD
   Rotter, JI
   Weinreb, RN
AF Zangwill, Linda M.
   Ayyagari, Radha
   Liebmann, Jeffrey M.
   Girkin, Christopher A.
   Feldman, Robert
   Dubiner, Harvey
   Dirkes, Keri A.
   Holmann, Matthew
   Williams-Steppe, Eunice
   Hammel, Naama
   Saunders, Luke J.
   Vega, Suzanne
   Sandow, Kevin
   Roll, Kathryn
   Slight, Rigby
   Auerbach, Daniel
   Samuels, Brian C.
   Panarelli, Joseph F.
   Mitchell, John P.
   Al-Aswad, Lama A.
   Park, Sung Chul
   Tello, Celso
   Cotliar, Jeremy
   Bansal, Rajendra
   Sidoti, Paul A.
   Cioffi, George A.
   Blumberg, Dana
   Ritch, Robert
   Bell, Nicholas P.
   Blieden, Lauren S.
   Davis, Garvin
   Medeiros, Felipe A.
   Ng, Maggie C. Y.
   Das, Swapan K.
   Palmer, Nicholette D.
   Divers, Jasmin
   Langefeld, Carl D.
   Freedman, Barry I.
   Bowden, Donald W.
   Christopher, Mark A.
   Chen, Yii-der I.
   Guo, Xiuqing
   Taylor, Kent D.
   Rotter, Jerome I.
   Weinreb, Robert N.
CA African Descent Glaucoma
TI The African Descent and Glaucoma Evaluation Study (ADAGES) III
   Contribution of Genotype to Glaucoma Phenotype in African Americans:
   Study Design and Baseline Data
SO OPHTHALMOLOGY
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; GENOME-WIDE ASSOCIATION; RARE-VARIANT ASSOCIATION;
   CENTRAL CORNEAL THICKNESS; OPTIC-NERVE; COMMON VARIANTS;
   INTRAOCULAR-PRESSURE; SUSCEPTIBILITY LOCI; RACIAL-DIFFERENCES;
   NEURORETINAL RIM
AB Purpose: To describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III.
   Design: Cross-sectional, case-control study.
   Participants: Three thousand two hundred sixty-six glaucoma patients and control participants without glaucoma of African or European descent were recruited from 5 study centers in different regions of the United States.
   Methods: Individuals of African descent (AD) and European descent (ED) with primary open-angle glaucoma (POAG) and control participants completed a detailed demographic and medical history interview. Standardized height, weight, and blood pressure measurements were obtained. Saliva and blood samples to provide serum, plasma, DNA, and RNA were collected for standardized processing. Visual fields, stereoscopic disc photographs, and details of the ophthalmic examination were obtained and transferred to the University of California, San Diego, Data Coordinating Center for standardized processing and quality review.
   Main Outcome Measures: Participant gender, age, race, body mass index, blood pressure, history of smoking and alcohol use in POAG patients and control participants were described. Ophthalmic measures included intraocular pressure, visual field mean deviation, central corneal thickness, glaucoma medication use, or past glaucoma surgery. Ocular conditions, including diabetic retinopathy, age-related macular degeneration, and past cataract surgery, were recorded.
   Results: The 3266 ADAGES III study participants in this report include 2146 AD POAG patients, 695 ED POAG patients, 198 AD control participants, and 227 ED control participants. The AD POAG patients and control participants were significantly younger (both, 67.4 years) than ED POAG patients and control participants (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared with ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all P < 0.001). Family history of glaucoma did not differ between AD and ED POAG patients.
   Conclusions: With its large sample size, extensive specimen collection, and deep phenotyping of AD and ED glaucoma patients and control participants from different regions in the United States, the ADAGES III genomics study will address gaps in our knowledge of the genetics of POAG in this high-risk population. (C) 2017 by the American Academy of Ophthalmology
C1 [Zangwill, Linda M.; Ayyagari, Radha; Dirkes, Keri A.; Holmann, Matthew; Williams-Steppe, Eunice; Hammel, Naama; Saunders, Luke J.; Vega, Suzanne; Slight, Rigby; Auerbach, Daniel; Medeiros, Felipe A.; Christopher, Mark A.; Weinreb, Robert N.] Univ Calif San Diego, Dept Ophthalmol, Hamilton Glaucoma Ctr, Shiley Eye Inst, 9500 Gilman Dr, La Jolla, CA 92093 USA.
   [Liebmann, Jeffrey M.; Mitchell, John P.; Cotliar, Jeremy; Bansal, Rajendra; Cioffi, George A.; Blumberg, Dana] Columbia Univ, Bernard & Shirlee Brown Glaucoma Res Lab, Harkness Eye Inst, Med Ctr, New York, NY USA.
   [Girkin, Christopher A.; Samuels, Brian C.] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL 35294 USA.
   [Feldman, Robert; Al-Aswad, Lama A.; Bell, Nicholas P.; Blieden, Lauren S.; Davis, Garvin] Univ Texas Hlth Sci Ctr Houston UTHlth, Ruiz Dept Ophthalmol & Visual Sci, McGovern Med Sch, Houston, TX USA.
   [Dubiner, Harvey] Eye Care Ctr Management Inc, Marrow, GA USA.
   [Sandow, Kevin; Roll, Kathryn; Chen, Yii-der I.; Guo, Xiuqing; Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.
   [Sandow, Kevin; Roll, Kathryn; Chen, Yii-der I.; Guo, Xiuqing; Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA.
   [Panarelli, Joseph F.; Park, Sung Chul; Tello, Celso; Sidoti, Paul A.; Ritch, Robert] New York Eye & Ear Infirm Mt Sinai, Einhorn Clin Res Ctr, New York, NY USA.
   [Ng, Maggie C. Y.; Palmer, Nicholette D.; Bowden, Donald W.] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.
   [Ng, Maggie C. Y.; Palmer, Nicholette D.; Freedman, Barry I.; Bowden, Donald W.] Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.
   [Das, Swapan K.] Wake Forest Sch Med, Dept Internal Med, Med Ctr Blvd, Winston Salem, NC USA.
   [Das, Swapan K.; Palmer, Nicholette D.; Divers, Jasmin; Langefeld, Carl D.; Freedman, Barry I.] Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA.
   [Palmer, Nicholette D.; Bowden, Donald W.] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA.
   [Divers, Jasmin; Langefeld, Carl D.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
   [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Nephrol Sect, Winston Salem, NC USA.
C3 University of California System; University of California San Diego;
   Columbia University; University of Alabama System; University of Alabama
   Birmingham; University of Texas System; University of Texas Health
   Science Center Houston; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; Lundquist Institute; University of California System; University
   of California Los Angeles; University of California Los Angeles Medical
   Center; New York Eye & Ear Infirmary of Mount Sinai; Wake Forest
   University; Wake Forest University; Wake Forest University; Wake Forest
   University; Wake Forest University; Wake Forest University; Wake Forest
   University
RP Weinreb, RN (通讯作者)，Univ Calif San Diego, Dept Ophthalmol, Hamilton Glaucoma Ctr, Shiley Eye Inst, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM rweinreb@ucsd.edu
RI Rotter, Jerome/AAY-6598-2021
OI Feldman, Robert/0000-0001-8586-6345; Girkin,
   Christopher/0000-0002-5781-7682; Al-Aswad, Lama/0000-0003-2440-9559
FU National Eye Institute, National Institutes of Health, Bethesda,
   Maryland [EY023704, P30EY022589, EY110008, EY019869, EY021818]; National
   Institutes of Health [R01 DK087914, R01 DK066358, R01 DK053591, U01
   DK105556, R01 HL56266, R01 DK070941, DRC DK063491, CTSI UL1TR001881];
   EyeSight Foundation of Alabama; Research to Prevent Blindness, Inc., New
   York, New York; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
   [UL1TR001881] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [P30EY022589, R01EY023704, T32EY026590] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
   [R01DK066358, P30DK063491, U01DK105556] Funding Source: NIH RePORTER
FX Supported by the National Eye Institute, National Institutes of Health,
   Bethesda, Maryland (grant nos.: EY023704, P30EY022589, EY110008,
   EY019869, and EY021818); and the National Institutes of Health (grant
   nos.: R01 DK087914, R01 DK066358, R01 DK053591, U01 DK105556, R01
   HL56266, R01 DK070941, DRC DK063491, and CTSI UL1TR001881); the EyeSight
   Foundation of Alabama (C.A.G.); and Research to Prevent Blindness, Inc.,
   New York, New York (C.A.G.).
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NR 94
TC 9
Z9 9
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JAN
PY 2019
VL 126
IS 1
BP 156
EP 170
DI 10.1016/j.ophtha.2017.11.031
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HE6PG
UT WOS:000453531300036
PM 29361356
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Eisenbarth, W
   Richert, J
   Mackeben, M
AF Eisenbarth, Werner
   Richert, Johann
   Mackeben, Manfred
TI Testing macular letter recognition - reliability and influence of
   refraction errors
SO CLINICAL AND EXPERIMENTAL OPTOMETRY
LA English
DT Article
DE age&#8208; related macular degeneration; letter recognition; macular
   mapping; peripheral vision; refraction; test&#8208; retest; visual field
ID VISUAL-ACUITY; CONTRAST SENSITIVITY; DIOPTRIC BLUR; MAPPING TEST;
   THRESHOLDS; REPEATABILITY; TARGETS; DEFOCUS; IDENTIFICATION; VISION
AB Purpose The goal was the validation of the Macular Mapping Test (MMT) for clinical use. We studied its susceptibility to blur caused by refractive errors and its test-retest reliability. Methods We tested letter recognition in 33 target locations in the central visual field (10 degrees radius) at two contrast levels, 10 and 100 per cent. Healthy subjects were either young (mean: 25.7-years) or elderly (mean: 67.0-years). A third group (patients with age-related macular degeneration, mean age: 76.4-years) were tested with their habitual optical correction and subsequently with optimal correction. The influence of refractive errors on performance was measured only for the healthy subgroups. All visual acuities were measured at 6.0 and 0.4 metres. Outcome measure was the 'general field score' (GFS), a single number expressing the overall level of letter recognition performance. Results The general field score versus refractive error showed a mean loss of 3.9 points per dioptre and 5.9 points per dioptre in young subjects at 100 and 10 per cent contrast, respectively. In elderly subjects, mean losses were 2.6 points per dioptre and 5.5 points per dioptre for 100 and 10 per cent contrast, respectively. The general field score ratio (GFS at 10 per cent divided by GFS at 100 per cent) shows a decrease of eight per cent for the young group and 11 per cent for the elderly group. Performance increased after improvement of the refractive status in the AMD group: At 100 per cent contrast, the general field score increase from 21.5 to 24.1 (p < 0.008) was significant but not at 10 per cent contrast. Mean increase of acuity with the optimal correction was 0.32 to 0.46 decimal for distance (p = 0.018) and 0.28 to 0.44 decimal near (p = 0.018). Test-retest reliability was good but dependent on contrast. Conclusions At both contrasts, performance declined with increasing blur caused by refractive errors. The slope of this decline is more pronounced at the lower contrast. In healthy subjects, optical blur beyond 1.00 D can cause significant performance losses.
C1 [Eisenbarth, Werner] Munich Univ Appl Sci, Dept Optometry Ophthalm Opt, Munich, Germany.
   [Richert, Johann] Univ Appl Sci, Dept Optometry, Aalen, Germany.
   [Mackeben, Manfred] Smith Kettlewell Eye Res Inst, 2232 Webster St, San Francisco, CA 94115 USA.
C3 University of Munich; The Smith-Kettlewell Eye Research Institute
RP Eisenbarth, W (通讯作者)，Munich Univ Appl Sci, Dept Optometry Ophthalm Opt, Munich, Germany.
EM werner.eisenbarth@hm.edu
OI Eisenbarth, Werner/0000-0003-2142-6513
FU German Zentralverband fur Augenoptiker
FX This research received no specific grant from any funding agency in the
   public, commercial, or not-for-profit sectors. W Eisenbarth PhD was
   supported by a travel grant to visit the ARVO meeting 2012, funded by
   the German Zentralverband fur Augenoptiker.
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NR 45
TC 0
Z9 0
U1 0
U2 3
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0816-4622
EI 1444-0938
J9 CLIN EXP OPTOM
JI Clin. Exp. Optom.
PD JUL 1
PY 2016
VL 99
IS 4
BP 322
EP 327
DI 10.1111/cxo.12360
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA VJ8RC
UT WOS:000640412000004
PM 27087542
OA Bronze
DA 2022-11-30
ER

PT J
AU De Groef, L
   Andries, L
   Lemmens, K
   Van Hove, I
   Moons, L
AF De Groef, Lies
   Andries, Lien
   Lemmens, Kim
   Van Hove, Inge
   Moons, Lieve
TI Matrix metalloproteinases in the mouse retina: a comparative study of
   expression patterns and MMP antibodies
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Matrix metalloproteinase; Retina; Immunohistochemistry; Western blot;
   Antibodies
ID GANGLION-CELL DEATH; PRIMARY OPEN-ANGLE; OPTIC-NERVE TRANSECTION;
   DIABETIC-RETINOPATHY; EXPERIMENTAL GLAUCOMA; INTRAOCULAR-PRESSURE;
   INHIBITORS; MATRIX-METALLOPROTEINASE-9; PROTEASES; POLYMORPHISMS
AB Background: Matrix metalloproteinases (MMPs), a family of Zn2+-dependent endoproteases, have been shown to act as fine regulators of both health and disease. Limited research revealed that they are essential to maintaining ocular physiology and inordinate MMP activities have been linked to several neurodegenerative disorders of the retina, including age-related macular degeneration, proliferative diabetic retinopathy and glaucomatous optic neuropathies (GONs). Nevertheless, a clear definition of their pathology-exacerbating and/or -resolving actions is lacking, especially in the context of GONs, as most studies thus far merely focused on expression profiling in human patients. Therefore, in an initial step towards an improved understanding of MMP functions in the retina, we studied the spatial expression pattern of MMP-2, -3, -9 and MT1-MMP in the healthy mouse retina.
   Methods: The spatial expression pattern of MMP-2, -3, -9 and MT1-MMP was studied in the healthy mouse retina via immunohistochemical stainings, and immunoreactivity profiles were compared to existing literature. Moreover, we considered sensitivity and specificity issues with commercially available MMP antibodies via Western blot.
   Results: Basal expression of MMP-2,-3, -9 and MT1-MMP was found in the retina of healthy, adult mice. MMP-2 expression was seen in Muller glia, predominantly in their end feet, which is in line with available literature. MMP-3 expression was described for the first time in the retina, and was observed in vesicle-like structures along the radial fibers of Muller glia. MMP-9 expression, about which still discords exists, was seen in microglia and in a sparse subset of (apoptosing) RGCs. MT1-MMP localization was for the first time studied in adult mice and was found in RGC axons and Muller glia, mimicking the MT1-MMP expression pattern seen in rabbits and neonatal mice. Moreover, one antibody was selected for each MMP, based on its staining pattern in Western blot.
   Conclusions: The present MMP immunoreactivity profiles in the mouse retina and validation of MMP antibodies, can be instrumental to study MMP expression in mouse models of ocular pathologies and to compare these expression profiles to observations from clinical studies, which would be a first step in the disentanglement of the exact role MMPs in ocular/retinal diseases.
C1 [De Groef, Lies; Andries, Lien; Lemmens, Kim; Van Hove, Inge; Moons, Lieve] Katholieke Univ Leuven, Dept Biol, Lab Neural Circuit Dev & Regenerat, Anim Physiol & Neurobiol Sect, B-3000 Leuven, Belgium.
C3 KU Leuven
RP Moons, L (通讯作者)，Katholieke Univ Leuven, Dept Biol, Lab Neural Circuit Dev & Regenerat, Anim Physiol & Neurobiol Sect, Naamsestr 61,Box 2464, B-3000 Leuven, Belgium.
EM lieve.moons@bio.kuleuven.be
RI ; De Groef, Lies/K-3296-2015
OI Moons, Lieve (Godelieve)/0000-0003-0186-1411; De Groef,
   Lies/0000-0002-3329-3474; Van Hove, Inge/0000-0002-3125-0438
FU KU Leuven Research Council (KU Leuven, Belgium) [BOF-OT/10/033];
   Hercules Foundation (Belgium) [AKUL-09-038, G.05311.10]; Flemish
   government agency
FX The authors would like to thank Lut Noterdaeme and Ingrid Proven
   (Laboratory of Neural Circuit Development and Regeneration, KU Leuven)
   for their excellent technical assistance. This work was supported by the
   KU Leuven Research Council (KU Leuven, Belgium, BOF-OT/10/033), the
   Hercules Foundation (Belgium, AKUL-09-038, AKUL1309), the Research
   Foundation Flanders (FWO-Vlaanderen, Belgium, G.05311.10) and the
   Flemish government agency for Innovation by Science and Technology
   (IWT-Vlaanderen, Belgium, fellowships to LDG, KM and IVH).
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NR 60
TC 19
Z9 19
U1 2
U2 7
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD DEC 29
PY 2015
VL 15
AR 187
DI 10.1186/s12886-015-0176-y
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DA1AD
UT WOS:000367527800003
PM 26714639
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Richard, G
   Mones, J
   Wolf, S
   Korobelnik, JF
   Guymer, R
   Goldstein, M
   Norenberg, C
   Sandbrink, R
   Zeitz, O
AF Richard, Gisbert
   Mones, Jordi
   Wolf, Sebastian
   Korobelnik, Jean Francois
   Guymer, Robyn
   Goldstein, Michaella
   Norenberg, Christiane
   Sandbrink, Rupert
   Zeitz, Oliver
TI Scheduled versus Pro Re Nata Dosing in the VIEW Trials
SO OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; VEGF-TRAP; RANIBIZUMAB
AB Purpose: To analyze visual acuity (VA) outcomes before and after preplanned treatment regimen change in the VIEW studies at week 52 (W52).
   Design: Multiple post hoc analyses for retrospectively defined subgroups in 2 multicenter, multinational, double-masked trials.
   Participants: Two thousand four hundred fifty-seven neovascular age-related macular degeneration (AMD) patients.
   Methods: Patients were randomized to treatment with 0.5 mg ranibizumab given monthly, a 0.5-mg or 2-mg intravitreal aflibercept injection given monthly, or 2 mg intravitreal aflibercept given every other month, after 3 initial monthly doses, up to W52. From W52 through W96, patients received their original dosing assignment using a capped pro re nata (PRN) regimen, with defined retreatment criteria based on VA and morphologic signs of disease activity and mandatory dosing at least every 12 weeks.
   Main Outcome Measures: Best-corrected VA (BCVA) and optical coherence tomography assessments were mandatory at all visits from baseline to W96. Outcomes were changes in BCVA and central retinal thickness. Outcomes were evaluated in all patients who completed 2 years of the VIEW studies using the last observation carried forward method for missing data at interim visits.
   Results: After W52, approximately 20% of patients lost 5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more across all treatment arms with PRN treatment. Patients who met the retreatment criterion of loss of 5 ETDRS letters or more in the first quarter of the PRN dosing phase did not recover; mean final VA loss across the 4 study arms was -4.4 to -5.8 letters. Outcomes of these patients up to W52 were indistinguishable from those of the overall population. There were no differences between groups in serious ocular adverse events or Anti-Platelet Trialists' Collaboration arterial thromboembolic events through W96.
   Conclusions: These analyses suggest that there are subgroups of patients for whom VA outcomes in the second year of the VIEW studies were less stable than in the first year and for whom W52 seems to be an important inflection point. Although alternate reasons specific to the nature of the underlying AMD cannot be fully excluded, the switch in treatment regimen at W52 is a plausible explanation. (C) 2015 by the American Academy of Ophthalmology.
C1 [Richard, Gisbert; Zeitz, Oliver] Univ Med Ctr Hamburg Eppendorf, Dept Ophthalmol, D-20246 Hamburg, Germany.
   [Mones, Jordi] Hosp Quiron Teknon, Inst Macula & Retina, Barcelona, Spain.
   [Mones, Jordi] Barcelona Macula Fdn, Barcelona, Spain.
   [Wolf, Sebastian] Univ Bern, Inselspital, Univ Hosp Bern, Dept Ophthalmol, CH-3010 Bern, Switzerland.
   [Korobelnik, Jean Francois] Ctr Hosp Univ Bordeaux, Serv Ophtalmol, Bordeaux, France.
   [Korobelnik, Jean Francois] Univ Bordeaux, Inst Sante Publ Epidemiol & Dev, Bordeaux, France.
   [Korobelnik, Jean Francois] INSERM, Ctr Epidemiol Biostat, Bordeaux, France.
   [Guymer, Robyn] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Goldstein, Michaella] Tel Aviv Med Ctr & Sch Med, Tel Aviv, Israel.
   [Goldstein, Michaella] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
   [Norenberg, Christiane; Sandbrink, Rupert; Zeitz, Oliver] Bayer Pharma AG, Berlin, Germany.
   [Sandbrink, Rupert] Univ Dusseldorf, Dept Neurol, Dusseldorf, Germany.
C3 University of Hamburg; University Medical Center Hamburg-Eppendorf;
   University of Bern; University Hospital of Bern; CHU Bordeaux;
   UDICE-French Research Universities; Universite de Bordeaux; Institut
   National de la Sante et de la Recherche Medicale (Inserm); Centre for
   Eye Research Australia; Royal Victorian Eye & Ear Hospital; University
   of Melbourne; Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv
   University; Sackler Faculty of Medicine; Bayer AG; Bayer Healthcare
   Pharmaceuticals; Heinrich Heine University Dusseldorf
RP Richard, G (通讯作者)，Univ Med Ctr Hamburg Eppendorf, Dept Ophthalmol, Martinistr 52, D-20246 Hamburg, Germany.
EM richard@uke.de
RI Zeitz, Oliver/AAJ-9728-2021; KOROBELNIK, Jean-Francois/A-5448-2016;
   mones, jordi/CAJ-2963-2022; Wolf, Sebastian/B-8782-2008
OI mones, jordi/0000-0003-3685-2160; Wolf, Sebastian/0000-0002-7467-7028;
   Guymer, Robyn/0000-0002-9441-4356
FU Bayer HealthCare (Berlin, Germany); Pfizer (Cambridge, MA); Carl Zeiss
   Meditec (Jena, Germany); Novartis AG (Basel, Switzerland); Pixium Vision
   (Paris, France); Consultant - Carl Zeiss Meditec (Jena, Germany)
FX The author(s) have made the following disclosure(s): G.R.: Financial
   support - Bayer HealthCare (Berlin, Germany), Pfizer (Cambridge, MA),
   Carl Zeiss Meditec (Jena, Germany), Novartis AG (Basel, Switzerland),
   Pixium Vision (Paris, France); Consultant - Carl Zeiss Meditec (Jena,
   Germany), Pixium Vision (Paris, France).
CR Brown DM, 2006, NEW ENGL J MED, V355, P1432, DOI 10.1056/NEJMoa062655
   Busbee BG, 2013, OPHTHALMOLOGY, V120, P1046, DOI 10.1016/j.ophtha.2012.10.014
   Chakravarthy U, 2012, OPHTHALMOLOGY, V119, DOI 10.1016/j.ophtha.2012.04.015
   Economides AN, 2003, NAT MED, V9, P47, DOI 10.1038/nm811
   Heier JS, 2012, OPHTHALMOLOGY, V119, P2537, DOI 10.1016/j.ophtha.2012.09.006
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NR 10
TC 37
Z9 38
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD DEC
PY 2015
VL 122
IS 12
BP 2497
EP 2503
DI 10.1016/j.ophtha.2015.08.014
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CZ4EZ
UT WOS:000367057500029
PM 26477840
DA 2022-11-30
ER

PT J
AU Verhoeven, VJM
   Wong, KT
   Buitendijk, GHS
   Hofman, A
   Vingerling, JR
   Klaver, CCW
AF Verhoeven, Virginie J. M.
   Wong, King T.
   Buitendijk, Gabrielle H. S.
   Hofman, Albert
   Vingerling, Johannes R.
   Klaver, Caroline C. W.
TI Visual Consequences of Refractive Errors in the General Population
SO OPHTHALMOLOGY
LA English
DT Article
ID PATHOLOGICAL MYOPIA; OLDER POPULATION; UNITED-STATES; PREVALENCE;
   METAANALYSIS; PROGRESSION; RETINOPATHY; ROTTERDAM; BLINDNESS; ETIOLOGY
AB Objective: To study the frequency and causes of visual impairment in relation to refractive error.
   Design: Population-based cohort study.
   Participants: A total of 6597 participants from Rotterdam Study I (baseline and 4 follow-up examinations) and 2579 participants from Rotterdam Study II (baseline and 2 follow-up examinations), all 55 years or older, were included.
   Methods: Participants underwent an extensive ophthalmic examination, including best-corrected visual acuity and objective refraction, fundus photography, visual field perimetry, and optical coherence tomography imaging of macula and optic disc. We calculated cumulative risks and odds ratios of visual impairment for various refractive error categories and determined causes by using all screening information as well as medical records.
   Main Outcome Measures: Unilateral and bilateral low vision (World Health Organization [WHO] criteria, VA <0.3 and VA >= 0.05; United States (US) criteria, VA <0.5 and VA >= 0.1) and blindness (WHO criteria, VA <0.05; US criteria, VA<0.1).
   Results: Cumulative risks of visual impairment ranged from virtually 0 in all refractive error categories at 55 years of age to 9.5% (standard error, 0.01) for emmetropia and 15.3% (standard error, 0.06) for high hyperopia to 33.7% (standard error, 0.08) for high myopia at 85 years of age. The major causes of visual impairment in highly hyperopic persons were age-related macular degeneration (AMD), cataract, and combined causes (each 25%); in highly myopic persons, the major cause was myopic macular degeneration (38.9%). The major causes of visual impairment for the other refractive error categories were AMD and cataract. Compared with those with emmetropia, those with high myopia had a significantly increased lifetime risk of visual impairment; those with -6 diopters (D) or less and -10 D or more had an odds ratio (OR) risk of 3.4 (95% confidence interval [CI], 1.4-8.2) of visual impairment; those with less than -10 D had an OR of 22.0 (95% CI, 9.2-52.6).
   Conclusions: Of all refractive errors, highmyopia has themost severe visual consequences. Irreversiblemacular pathologic features are the most common cause of visual impairment in this group. (C) 2015 by the American Academy of Ophthalmology.
C1 [Verhoeven, Virginie J. M.; Wong, King T.; Buitendijk, Gabrielle H. S.; Vingerling, Johannes R.; Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, NL-3000 CA Rotterdam, Netherlands.
   [Verhoeven, Virginie J. M.; Buitendijk, Gabrielle H. S.; Hofman, Albert; Vingerling, Johannes R.; Klaver, Caroline C. W.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
   [Hofman, Albert] Netherlands Consortium Hlth Ageing, Netherlands Genom Initiat, The Hague, Netherlands.
C3 Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam;
   Erasmus MC
RP Klaver, CCW (通讯作者)，Erasmus MC, Dept Ophthalmol, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM c.c.w.klaver@erasmusmc.nl
RI Klaver, Caroline C.W./A-2013-2016
OI Verhoeven, Virginie/0000-0001-7359-7862; Klaver,
   Caroline/0000-0002-2355-5258
FU Netherlands Organization of Scientific Research (NWO) [Vidi 91796357];
   NWO Investments [175.010.2005.011, 911-03-012]; Netherlands Genomics
   Initiative (NGI)/ NWO [050-060-810]; Erasmus Medical Center and Erasmus
   University, Rotterdam, The Netherlands; Netherlands Organization for
   Health Research and Development (ZonMw); UitZicht, Stichting Combined
   Ophthalmic Research Rotterdam (CORR); Research Institute for Diseases in
   the Elderly [014-93-015, RIDE2]; Ministry of Education, Culture and
   Science; Ministry for Health, Welfare and Sports; European Commission
   (DG XII); Municipality of Rotterdam; Netherlands Genomics Initiative/
   NWO, Rotterdam, The Netherlands; Center for Medical Systems Biology of
   NGI; Lijf en Leven; M.D. Fonds; Henkes Stichting; Stichting Nederlands
   Oogheelkundig Onderzoek; Swart van Essen; Bevordering van Volkskracht;
   Blindenhulp; Landelijke Stichting voor Blinden en Slechtzienden;
   Rotterdamse Vereniging voor Blindenbelangen; OOG; Algemene Nederlandse
   Vereniging ter Voorkoming van Blindheid; Rotterdam Eye Hospital Research
   Foundation; Erasmus Trustfonds; Topcon Europe
FX Supported by the Netherlands Organization of Scientific Research (NWO;
   grant no.: Vidi 91796357 [C.C.W.K.]); NWO Investments (grant no.:
   175.010.2005.011, 911-03-012 to the Rotterdam Study); the Netherlands
   Genomics Initiative (NGI)/ NWO (grant no.: 050-060-810 to the Rotterdam
   Study); Erasmus Medical Center and Erasmus University, Rotterdam, The
   Netherlands; Netherlands Organization for Health Research and
   Development (ZonMw); UitZicht, Stichting Combined Ophthalmic Research
   Rotterdam (CORR); the Research Institute for Diseases in the Elderly
   (grant no.: 014-93-015, RIDE2); the Ministry of Education, Culture and
   Science, the Ministry for Health, Welfare and Sports, the European
   Commission (DG XII); the Municipality of Rotterdam, The Netherlands
   Genomics Initiative/ NWO, Rotterdam, The Netherlands; Center for Medical
   Systems Biology of NGI; Lijf en Leven; M.D. Fonds; Henkes Stichting;
   Stichting Nederlands Oogheelkundig Onderzoek; Swart van Essen;
   Bevordering van Volkskracht; Blindenhulp; Landelijke Stichting voor
   Blinden en Slechtzienden; Rotterdamse Vereniging voor Blindenbelangen;
   OOG; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid; the
   Rotterdam Eye Hospital Research Foundation; Erasmus Trustfonds; and
   Topcon Europe. The funding organizations had no role in the design and
   conduct of the study; the collection, management, analysis, and
   interpretation of the data; or the preparation, review, or approval of
   the manuscript.
CR Bar Dayan Y, 2005, INVEST OPHTH VIS SCI, V46, P2760, DOI 10.1167/iovs.04-0260
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NR 25
TC 84
Z9 90
U1 0
U2 33
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JAN
PY 2015
VL 122
IS 1
BP 101
EP 109
DI 10.1016/j.ophtha.2014.07.030
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AX1XK
UT WOS:000346737000025
PM 25208857
DA 2022-11-30
ER

PT J
AU Xu, HJ
   Li, QY
   Zou, T
   Yin, ZQ
AF Xu, Hao-Jue
   Li, Qi-You
   Zou, Ting
   Yin, Zheng-Qin
TI Development-related mitochondrial properties of retina pigment
   epithelium cells derived from hEROs
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE mitochondria; retinal organoids; retinal pigment epithelium cells; human
   embryonic stem cells; retinal degenerative diseases
ID EMBRYONIC STEM-CELLS; LONG-TERM SAFETY; MACULAR DEGENERATION;
   PROGRESSIVE STAGES; DIFFERENTIATION; RPE; PREVALENCE; METABOLISM;
   DEPRESSION; EXPRESSION
AB AIM: To explore the temporal mitochondrial characteristics of retinal pigment epithelium (RPE) cells obtained from human embryonic stem cells (hESC)-derived retinal organoids (hEROs-RPE), to verify the optimal period for using hEROs-RPE as donor cells from the aspect of mitochondria and to optimize RPE cell-based therapeutic strategies for age-related macular degeneration (AMD).
   METHODS: RPE cells were obtained from hEROs and from spontaneous differentiation (SD-RPE). The mitochondrial characteristics were analyzed every 20d from day 60 to 160. Mitochondrial quantity was measured by MitoTracker Green staining. Transmission electron microscopy (TEM) was adopted to assess the morphological features of the mitochondria, including their distribution, length, and cristae. Mitochondrial membrane potentials (MMPs) were determined by JC-1 staining and evaluated by flow cytometry, reactive oxygen species (ROS) levels were evaluated by flow cytometry, and adenosine triphosphate (ATP) levels were measured by a luminometer. Differences between two groups were analyzed by the independent-samples t-test, and comparisons among multiple groups were made using one-way ANOVA or Kruskal-Wallis H test when equal variance was not assumed.
   RESULTS: hEROs-RPE and SD-RPE cells from day 60 to 160 were successfully differentiated from hESCs and expressed RPE markers (Pax6, MITF, Bestrophin-1, RPE65, Cralbp). RPE features, including a cobblestone-like morphology with tight junctions (ZO-1), pigments and microvilli, were also observed in both hEROs-RPE and SD-RPE cells. The mitochondrial quantities of hEROs-RPE and SD-RPE cells both peaked at day 80. However, the cristae of hEROs-RPE mitochondria were less mature and abundant than those of SD-RPE mitochondria at day 80, with hEROs-RPE mitochondria becoming mature at day 100. Both hEROs-RPE and SD-RPE cells showed low ROS levels from day 100 to 140 and maintained a normal MMP during this period. However, hEROs-RPE mitochondria maintained a longer time to produce high levels of ATP (from day 120 to 140) than SD-RPE cells (only day 120).
   CONCLUSION: hEROs-RPE mitochondria develop more slowly and maintain a longer time to supply high-level energy than SD-RPE mitochondria. From the mitochondrial perspective, hEROs-RPE cells from day 100 to 140 are an optimal cell source for treating AMD.
C1 [Xu, Hao-Jue; Li, Qi-You; Zou, Ting; Yin, Zheng-Qin] Army Med Univ, Mil Med Univ 3, Southwest Hosp, Southwest Eye Hosp, Chongqing 400038, Peoples R China.
   [Xu, Hao-Jue; Li, Qi-You; Zou, Ting; Yin, Zheng-Qin] Key Lab Visual Damage & Regenerat & Restorat Chon, Chongqing 400038, Peoples R China.
C3 Army Medical University
RP Zou, T; Yin, ZQ (通讯作者)，Army Med Univ, Mil Med Univ 3, Southwest Hosp, Southwest Eye Hosp, Chongqing 400038, Peoples R China.
EM zoutingcq@163.com; qinzyin@aliyun.com
FU National Key Research and Development Program of China
   [2018YFA01017302]; National Natural Science Foundation of China
   [82000945]
FX Supported by the National Key Research and Development Program of China
   (No. 2018YFA01017302); the National Natural Science Foundation of China
   (No.82000945).
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NR 74
TC 0
Z9 0
U1 1
U2 4
PU IJO PRESS
PI XI AN
PA NO 269 YOUYI EAST RD, XI AN, 710054, PEOPLES R CHINA
SN 2222-3959
EI 2227-4898
J9 INT J OPHTHALMOL-CHI
JI Int. J. Ophthalmol.
PD AUG 18
PY 2021
VL 14
IS 8
BP 1138
EP 1150
DI 10.18240/ijo.2021.08.02
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA TY4LS
UT WOS:000683756800002
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Charlson, ES
   Sankar, PS
   Miller-Ellis, E
   Regina, M
   Fertig, R
   Salinas, J
   Pistilli, M
   Salowe, RJ
   Rhodes, AL
   Merritt, WT
   Chua, M
   Trachtman, BT
   Gudiseva, HV
   Collins, DW
   Chavali, VRM
   Nichols, C
   Henderer, J
   Ying, GS
   Varma, R
   Jorgenson, E
   O'Brien, JM
AF Charlson, Emily S.
   Sankar, Prithvi S.
   Miller-Ellis, Eydie
   Regina, Meredith
   Fertig, Raymond
   Salinas, Julia
   Pistilli, Maxwell
   Salowe, Rebecca J.
   Rhodes, Allison L.
   Merritt, William T., III
   Chua, Michael
   Trachtman, Benjamin T.
   Gudiseva, Harini V.
   Collins, David W.
   Chavali, Venkata Ramana Murthy
   Nichols, Charles
   Henderer, Jeffrey
   Ying, Gui-shuang
   Varma, Rohit
   Jorgenson, Eric
   O'Brien, Joan M.
TI The Primary Open-Angle African American Glaucoma Genetics Study Baseline
   Demographics
SO OPHTHALMOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; FALSE DISCOVERY RATE; BALTIMORE EYE SURVEY;
   RISK-FACTORS; COMMON VARIANTS; HEART-FAILURE; HEALTH-CARE; FOLLOW-UP;
   VALIDITY; DISEASE
AB Purpose: To describe the baseline characteristics of the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study cohort, the largest African American population with primary open-angle glaucoma (POAG) recruited at a single institution (University of Pennsylvania [UPenn], Department of Ophthalmology, Scheie Eye Institute) to date.
   Design: Population-based, cross-sectional, case-control study.
   Participants: A total of 2520 African American subjects aged 35 years or more who were recruited from the greater Philadelphia, Pennsylvania area.
   Methods: Each subject underwent a detailed interview and eye examination. The interview assessed demographic, behavioral, medical, and ocular risk factors. Current ZIP codes surrounding UPenn were recorded and US census data were queried to infer socioeconomic status. The eye examination included measurement of visual acuity (VA) and intraocular pressure, and a detailed anterior and posterior segment examination, including gonioscopy, dilated fundus and optic disc examination, visual fields, stereo disc photography, optical coherence tomography, and measurement of central corneal thickness.
   Main Outcome Measures: The baseline characteristics of gender, age, and glaucoma diagnosis were collected. Body mass index (BMI), hypertension, diabetes, alcohol and tobacco use, ocular conditions (including blindness, cataract, nonproliferative diabetic retinopathy, and age-related macular degeneration), and use of ocular medication and surgery were examined. Median population density, income, education level, and other socioeconomic measures were determined for the study cohort.
   Results: Of the 2520 African Americans recruited to the POAAGG study to date, 2067 (82.0%), including 807 controls and 1260 POAG cases, met all inclusion criteria and completed the detailed clinical ocular examination. Cases were more likely to have a lower BMI (P < 0.01) and report a history of blindness (VA of <= 20/200; P < 0.001), whereas controls were more likely to have diabetes (P < 0.001), have nonproliferative diabetic retinopathy (P = 0.02), and be female (P < 0.001). Study participants were drawn largely from predominantly African American neighborhoods of low income, high unemployment, and lower education surrounding UPenn.
   Conclusions: The POAAGG study has currently recruited more than 2000 African Americans eligible for a POAG genetics study. Blindness and low BMI were significantly associated with POAG. This population was predominantly recruited from neighborhoods whose population income exists at or near the federal poverty level. (C) 2015 by the American Academy of Ophthalmology.
C1 [Charlson, Emily S.; Sankar, Prithvi S.; Miller-Ellis, Eydie; Regina, Meredith; Fertig, Raymond; Salinas, Julia; Pistilli, Maxwell; Salowe, Rebecca J.; Rhodes, Allison L.; Merritt, William T., III; Chua, Michael; Trachtman, Benjamin T.; Gudiseva, Harini V.; Collins, David W.; Chavali, Venkata Ramana Murthy; Nichols, Charles; Ying, Gui-shuang; O'Brien, Joan M.] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA.
   [Henderer, Jeffrey] Temple Univ, Sch Med, Dept Ophthalmol, Philadelphia, PA USA.
   [Varma, Rohit] Univ Illinois, Illinois Eye & Ear Infirm, Chicago, IL USA.
   [Jorgenson, Eric] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
C3 University of Pennsylvania; Pennsylvania Medicine; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); Temple University;
   University of Illinois System; University of Illinois Chicago;
   University of Illinois Chicago Hospital; Kaiser Permanente
RP O'Brien, JM (通讯作者)，Univ Penn, Scheie Eye Inst, 51 N 39th St, Philadelphia, PA 19104 USA.
EM joan.obrien@uphs.upenn.edu
FU National Eye Institute, Bethesda, Maryland [1RO1EY023557-01]; Department
   of Ophthalmology at the Perelman School of Medicine, UPenn,
   Philadelphia, Pennsylvania; F.M. Kirby Foundation; Research to Prevent
   Blindness [GFW8296]; Paul and Evanina Bell Mackall Foundation Trust;
   National Eye Institute, National Institutes of Health, Department of
   Health and Human Services, under eyeGENETM [HHSN260220700001C,
   HHSN263201200001C]; National Eye Institute; National Institutes of
   Health; Janssen; NATIONAL EYE INSTITUTE [P30EY001583, R01EY023557]
   Funding Source: NIH RePORTER
FX The author(s) have made the following disclosure( s): E.S.C., P.S.S.,
   E.M-E., M.R., J.S., R.J.S., A.L.R., B.T.T., M.C., D.W.C., H.V.G.,
   V.R.M.C., C.N. and J.M.O. received funding from the National Eye
   Institute. M.P. received funding from the National Institutes of Health.
   G.-S.Y. received funding from the National Eye Institute and personal
   fees from Janssen.; Supported by the National Eye Institute, Bethesda,
   Maryland (grant #1RO1EY023557-01) and the Department of Ophthalmology at
   the Perelman School of Medicine, UPenn, Philadelphia, Pennsylvania.
   Funds also were received from the F.M. Kirby Foundation, Research to
   Prevent Blindness (grant no. GFW8296), The Paul and Evanina Bell Mackall
   Foundation Trust, and the National Eye Institute, National Institutes of
   Health, Department of Health and Human Services, under eyeGENETM and
   contract nos. HHSN260220700001C and HHSN263201200001C. The sponsor or
   funding organization had no role in the design or conduct of this
   research.
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NR 47
TC 32
Z9 32
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD APR
PY 2015
VL 122
IS 4
BP 711
EP 720
DI 10.1016/j.ophtha.2014.11.015
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CE3EX
UT WOS:000351710100017
PM 25576993
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Thulliez, M
   Angoulvant, D
   Le Lez, ML
   Jonville-Bera, AP
   Pisella, PJ
   Gueyffier, F
   Bejan-Angoulvant, T
AF Thulliez, Marie
   Angoulvant, Denis
   Le Lez, Marie Laure
   Jonville-Bera, Annie-Pierre
   Pisella, Pierre-Jean
   Gueyffier, Francois
   Bejan-Angoulvant, Theodora
TI Cardiovascular Events and Bleeding Risk Associated With Intravitreal
   Antivascular Endothelial Growth Factor Monoclonal Antibodies Systematic
   Review and Meta-analysis
SO JAMA OPHTHALMOLOGY
LA English
DT Review
ID VERTEPORFIN PHOTODYNAMIC THERAPY; ARTERIAL THROMBOEMBOLIC EVENTS;
   OCCLUSION 12-MONTH OUTCOMES; MACULAR DEGENERATION; CANCER-PATIENTS;
   FACTOR INHIBITORS; CHOROIDAL NEOVASCULARIZATION; MYOCARDIAL-INFARCTION;
   SUSTAINED BENEFITS; PLASMA-LEVELS
AB IMPORTANCE Few data exist regarding the systemic safety of intravitreal antivascular endothelial growth factor (anti-VEGF) monoclonal antibody (mAb).
   OBJECTIVE To conduct a systematic review and meta-analysis to evaluate the risk of major cardiovascular and nonocular hemorrhagic events in patients with neovascular age-related macular degeneration (AMD), diabetes mellitus-associated macular edema (DME), or retinal vein occlusions (RVOs) who receive intravitreal anti-VEGF mAbs.
   DATA SOURCES The MEDLINE and Cochrane Central databases were searched for potentially eligible studies.
   STUDY SELECTION Randomized clinical trials comparing ranibizumab or bevacizumab with no anti-VEGF treatment, as well as those comparing ranibizumab with bevacizumab in patients with AMD, DME, or RVOs.
   DATA EXTRACTION AND SYNTHESIS We used a fixed-effects model and report the results as odds ratios (ORs) and 95% CIs.
   MAIN OUTCOMES AND MEASURES Primary end points were major cardiovascular and nonocular hemorrhagic events. Secondary end points were all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, venous thromboembolic events (VTEs), and hypertension.
   RESULTS Twenty-one trials that evaluated 9557 patients were retrieved. Anti-VEGF mAbs did not significantly increase the risk of major cardiovascular events (OR, 1.18; 95% CI, 0.81-1.71) or nonocular hemorrhagic events (OR, 1.42; 95% CI, 0.95-2.13) in treatment groups compared with control populations. Bevacizumab did not increase the risk of major cardiovascular events (OR, 0.94; 95% CI, 0.59-1.52) or nonocular hemorrhagic events (OR, 2.56; 95% CI, 0.78-8.38) compared with ranibizumab, but significantly increased VTEs (OR, 3.45; 95% CI, 1.25-9.54). Subgroup analysis showed a significant increase of nonocular hemorrhagic events in patients with AMD in ranibizumab vs control trials (OR, 1.57; 95% CI, 1.01-2.44). Anti-VEGF mAbs did not significantly increase overall mortality, cardiovascular mortality, stroke, myocardial infarction, VTEs, or hypertension.
   CONCLUSIONS AND RELEVANCE We showed that intravitreal anti-VEGF-mAbs were not associated with significant increases in major cardiovascular or nonocular hemorrhagic events, but studies and meta-analyses were not powered enough to correctly assess these risks. Increased risks of VTEs with bevacizumab and nonocular hemorrhagic events in older patients with AMD with ranibizumab should be cautiously interpreted because more safety data are needed.
C1 [Thulliez, Marie; Le Lez, Marie Laure; Pisella, Pierre-Jean] Hop Bretonneau, Ctr Hosp Reg Univ Tours, Dept Ophthalmol, F-37044 Tours 9, France.
   [Angoulvant, Denis] Trousseau Hosp, Ctr Hosp Reg Univ Tours, Dept Cardiol, Tours, France.
   [Angoulvant, Denis] Univ Tours, Equipe Accueil 4245, Tours, France.
   [Jonville-Bera, Annie-Pierre; Bejan-Angoulvant, Theodora] Hop Bretonneau, Ctr Hosp Reg Univ Tours, Dept Pharmacol, F-37044 Tours 9, France.
   [Gueyffier, Francois] Hosp Civils Lyon, Dept Clin Pharmacol, Lyon, France.
   [Gueyffier, Francois] CNRS, Unite Mixte Rech 5558, Villeurbanne, France.
   [Gueyffier, Francois] Univ Lyon 1, Fac Med, F-69365 Lyon, France.
   [Bejan-Angoulvant, Theodora] Univ Tours, Fac Med, Tours, France.
C3 CHU Tours; CHU Tours; Universite de Tours; CHU Tours; CHU Lyon; Centre
   National de la Recherche Scientifique (CNRS); CNRS - Institute of
   Ecology & Environment (INEE); VetAgro Sup; UDICE-French Research
   Universities; Universite Claude Bernard Lyon 1; Universite de
   Franche-Comte; Universite de Franche-Comte; Universite de Tours
RP Bejan-Angoulvant, T (通讯作者)，Hop Bretonneau, Ctr Hosp Reg Univ Tours, Pharmacol Clin, 2 Bd Tonnelle, F-37044 Tours 9, France.
EM theodora.angoulvant@univ-tours.fr
RI Gueyffier, François/B-8545-2008; Jonville-Bera,
   Annie-Pierre/L-9019-2015; Angoulvant, Denis/Q-9743-2019
OI Gueyffier, François/0000-0002-9921-0977; Angoulvant,
   Denis/0000-0003-0788-8092; Bejan-Angoulvant,
   Theodora/0000-0002-0018-9996
FU AstraZeneca; Novartis; Lilly; MSD; Servier Laboratories; Amgen; Bayer;
   Teva; Bristol-Myers Squibb; Janssen-Cilag; UCB Pharma; Urgo
   Pharmaceutical; Schering-Plough; Novo Nordisk; Trophos; Teikoku Pharma
FX Dr Angoulvant receives personal fees from AstraZeneca, Novartis, Lilly,
   MSD, Servier Laboratories, Amgen, and Bayer; grants from Lilly; and
   nonfinancial support from MSD; no funds were received for the present
   study. Dr Gueyffier receives nonfinancial support from Servier
   Laboratories; grants from Teva, Bristol-Myers Squibb, Lilly,
   Janssen-Cilag, UCB Pharma, Novartis, Urgo Pharmaceutical,
   Schering-Plough, Novo Nordisk, Trophos, and Teikoku Pharma; and has
   Novadiscovery shares; no funds were received for the present study. No
   other disclosures are reported.
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NR 65
TC 81
Z9 83
U1 0
U2 11
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD NOV
PY 2014
VL 132
IS 11
BP 1317
EP 1326
DI 10.1001/jamaophthalmol.2014.2333
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AT8WO
UT WOS:000345210100010
PM 25058694
OA Bronze
DA 2022-11-30
ER

PT J
AU Feng, JY
   Chen, XJ
   Sun, XJ
   Wang, FH
   Sun, XD
AF Feng, Jingyang
   Chen, Xunjie
   Sun, Xiangjun
   Wang, Fenghua
   Sun, Xiaodong
TI Expression of Endoplasmic Reticulum Stress Markers GRP78 and CHOP
   Induced by Oxidative Stress in Blue Light-Mediated Damage of
   A2E-Containing Retinal Pigment Epithelium Cells
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE N-retinylidene-N-retinylethanolamine; Endoplasmic reticulum stress;
   Oxidative stress; Glucose-related protein 78; Retinal pigment epithelium
ID UNFOLDED PROTEIN RESPONSE; ER STRESS; FUNDUS AUTOFLUORESCENCE;
   LIPOFUSCIN FLUOROPHORE; REGULATOR GRP78/BIP; A2E; PROTECTION;
   MECHANISMS; GADD153; HEALTH
AB Aims: Age-related lipofuscin N-retinylidene-N-retinylethanolamine (A2E) accumulated in human retinal pigment epithelium (RPE) cells confers susceptibility to blue light-mediated damage, which represents one pathogenesis of age-related macular degeneration. This study investigated the expression of 2 best-characterized endoplasmic reticulum (ER) stress markers, glucose-related protein 78 (GRP78) and C/EBP homologous protein (CHOP), as well as their regulation by oxidative stress after blue light-mediated damage of A2E-containing RPE cells. Methods: ARPE-19 cells were incubated with A2E (10, 25, 50 pm) for 2 h and exposed to blue light for 20 min. A2E distributions in RPE cells were assessed via laser scanning confocal microscope and liquid chromatography-mass spectrometry. Cell viability was measured by a Cell Titer 96 Aqueous One Solution cell proliferation assay. The quantity of intracellular reactive oxygen species (ROS) was detected by dihydroethidium fluorescence using flow cytometry. Expressions of GRP78 and CHOP were measured at both mRNA and protein levels. To examine the role of oxidative stress in regulating GRP78 and CHOP expression, RPE cells were pretreated with the antioxidant N-acetylcysteine (NAC) for 2 h. RNA interference of GRP78 performed by short hairpin RNA was used to evaluate the effect of GRP78 in blue light-mediated damage of RPE cells. Results: After blue light exposure, A2E-treated RPE cells showed a gradual decrease in cell viability and a particular increase in ROS levels. Meanwhile, the expressions of GRP78 and CHOP in A2E-treated RPE cells were significantly increased at different time points after illumination. Pretreatment with NAC attenuated the expression of 2 ER stress markers, especially CHOP in A2E and blue light-treated RPE cells. Silencing of GRP78 by RNA interference upregulated CHOP and caspase-12 expression as well as aggravated the blue light-mediated damage of A2E-laden RPE cells. Conclusion: RPE cells exhibited ROS accumulation and subsequent elevation of GRP78 and CHOP expression after A2E and blue light-induced damage. The ROS scavenger NAC diminished ER stress protein expression, suggesting a connection between ER and oxidative stress in blue light-mediated damage of A2E-containing RPE cells. Besides, GRP78 may play a protective role in it. (C) 2014 S. Karger AG, Basel
C1 [Feng, Jingyang; Chen, Xunjie; Wang, Fenghua; Sun, Xiaodong] Shanghai Jiao Tong Univ, Dept Ophthalmol, Sch Med, Shanghai Peoples Hosp 1, Shanghai 200080, Peoples R China.
   [Sun, Xiangjun] Shanghai Jiao Tong Univ, Sch Biol & Agr, Shanghai 200080, Peoples R China.
   [Wang, Fenghua; Sun, Xiaodong] Shanghai Key Lab Fundus Dis, Shanghai, Peoples R China.
C3 Shanghai Jiao Tong University; Shanghai Jiao Tong University
RP Sun, XD (通讯作者)，Shanghai Jiao Tong Univ, Dept Ophthalmol, Sch Med, Shanghai Peoples Hosp 1, 100 Hai Ning Rd, Shanghai 200080, Peoples R China.
EM xdsun@sjtu.edu.cn
OI Feng, Jingyang/0000-0001-6031-7980
FU National Natural Science Foundation of China [81271030, 81100678];
   National Basic Research Program (973 Program) [2011CB707506]; Shanghai
   Key Basic Research Grant [11JC141601]; Shanghai Scholar Leadership Grant
   [12XD1404100]; Shanghai Key Medical Research Grant [11JC1410600]
FX The authors thank Prof. Xiangjun Sun (Shanghai Jiao Tong University) and
   Qing Gu for their invaluable assistance in A2E synthesis. This study was
   supported by the National Natural Science Foundation of China (grants
   No. 81271030 and 81100678), National Basic Research Program (973
   Program; grant No. 2011CB707506), a Shanghai Key Basic Research Grant
   (11JC141601), Shanghai Scholar Leadership Grant (12XD1404100) and a
   Shanghai Key Medical Research Grant (11JC1410600).
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NR 42
TC 40
Z9 46
U1 1
U2 14
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2014
VL 52
IS 4
BP 224
EP 233
DI 10.1159/000363387
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AU5WU
UT WOS:000345675200007
PM 25402962
DA 2022-11-30
ER

PT J
AU Lee, BS
   Kymes, SM
   Nease, RF
   Sumner, W
   Siegfried, CJ
   Gordon, MO
AF Lee, Bryan S.
   Kymes, Steven M.
   Nease, Robert F., Jr.
   Sumner, Walton
   Siegfried, Carla J.
   Gordon, Mae O.
TI The impact of anchor point on utilities for 5 common ophthalmic diseases
SO OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; VISUAL FUNCTION QUESTIONNAIRE; DRY EYE DISEASE; TIME
   TRADE-OFF; MACULAR DEGENERATION; COST-EFFECTIVENESS; PHOTODYNAMIC
   THERAPY; DIABETIC-RETINOPATHY; GLAUCOMA PATIENTS; VALUES
AB Purpose: To elicit utilities on a perfect health and perfect vision scale for 5 common eye diseases.
   Design: Cross-sectional observational preference study.
   Participants: We included 434 patients: 58 with diabetic retinopathy, 99 with glaucoma, 44 with age-related macular degeneration (AMD), 124 with cataract; 109 with refractive error.
   Testing: Standard gamble utilities were estimated using a computer-based preference assessment interview platform.
   Main Outcome Measures: Standard gamble utilities, a quality-of-life measure that examines the willingness to accept a risk of death or unilateral blindness in return for perfect health or perfect vision.
   Results: Using the standard policy scale, where health equivalent to death is 0 and perfect health is 1, participants with asymptomatic diabetic retinopathy had a utility of 0.93. By comparison, symptomatic diabetics had a further utility loss of 0.14. Asymptomatic glaucoma participants had a utility of 0.92 with a decrease of 0.03 for early field loss and a further decrease of 0.03 with central field loss. Participants with AMD who had >= 20/100 better-eye visual acuity reported a utility of 0.89, whereas those with more severe AMD reported 0.76. However, neither clinical cataract opacity score nor refractive error correlated with utility. Adjustment for age and comorbidity did not alter these relationships. For the same participants, utilities measured with different anchor points-monocular blindness as 0 and perfect vision as 1-were lower, especially among participants with increased disease severity. The difference between utility assessed on this perfect vision-blindness scale and the perfect health-death scale ranged from 0.04 for those with severe refractive error to 0.19 for symptomatic diabetics and 0.37 for those with severe AMD.
   Conclusions: This paper elicits utilities with different anchor points from a previously unreported sample of 434 patients. Lower utility scores normally imply greater benefit with successful treatment or prevention of disease, but switching from the conventional policy scale to the perfect vision scale also consistently results in lower scores. Because most previous ophthalmic studies have used perfect vision as the upper anchor, the resulting utilities may not have been accurate.
C1 [Lee, Bryan S.; Kymes, Steven M.; Siegfried, Carla J.; Gordon, Mae O.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
   [Kymes, Steven M.; Gordon, Mae O.] Washington Univ, Sch Med, Dept Biostat, St Louis, MO USA.
   [Nease, Robert F., Jr.] Express Scripts Inc, St Louis, MO USA.
   [Sumner, Walton] Washington Univ, Sch Med, Dept Gen Med Sci, St Louis, MO USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Express
   Scripts Holding Company; Washington University (WUSTL)
RP Kymes, SM (通讯作者)，Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, Campus Box 8096 660 S Euclid, St Louis, MO 63110 USA.
RI Sumner, Walton/H-5045-2019
FU NATIONAL EYE INSTITUTE [R01EY011871] Funding Source: NIH RePORTER; NEI
   NIH HHS [R01EY011871] Funding Source: Medline
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NR 46
TC 49
Z9 49
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAY
PY 2008
VL 115
IS 5
BP 898
EP 903
DI 10.1016/j.ophtha.2007.06.008
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 297KA
UT WOS:000255614400023
PM 17826833
DA 2022-11-30
ER

PT J
AU Beck, TJ
   Burkanas, M
   Bagdonas, S
   Krivickiene, Z
   Beyer, W
   Sroka, R
   Baumgartner, R
   Rotomskis, R
AF Beck, Tobias J.
   Burkanas, Marius
   Bagdonas, Saulius
   Krivickiene, Zita
   Beyer, Wolfgang
   Sroka, Ronald
   Baumgartner, Reinhold
   Rotomskis, Ricardas
TI Two-photon photodynamic therapy of C6 cells by means of 5-aminolevulinic
   acid induced protoporphyrin IX
SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
LA English
DT Article
DE two-photon; TPE; photodynamic therapy; 5-aminolevulinic acid;
   protoporphyrin IX; C6 cells
ID PHOTOSENSITIZED PRODUCTION; CELLULAR-RESPONSE; LASER-PULSES; IN-VITRO;
   EXCITATION; ABSORPTION; OXYGEN; CYTOTOXICITY; PHOTON
AB Photodynamic therapy (PDT) has received increased attention as a treatment modality for malignant tumors as well as non-oncologic diseases such as age-related macular degeneration (AMD). An alternative to excite the photosensitizer by the common one-photon absorption is the method of two-photon excitation (TPE). This two-photon photodynamic therapy has the potential of improving the therapeutic outcome due to a highly localized photodynamic effect. The present study investigated the two-photon excited PDT performing in vitro experiments where C6 rat glioma cells were irradiated with a pulsed and focused fs Ti:sapphire laser emitting light at 800 nm. The irradiance distribution of the laser beam was carefully analyzed before the experiment and the applied irradiance was known for each position within the irradiated cell layer. Cells were divided into four groups and one group was incubated with 5-ALA and irradiated 4-5 h later. The survival of this group was tested after irradiation by means of ethidium bromide and acridine orange staining and compared to a control group, which was irradiated under the same conditions, but not incubated with 5-ALA before. Both groups showed necrotic areas depending on the applied irradiance, the value of which at the margin of the necrotic area could be deduced from its size. 5-ALA incubated cells became necrotic after irradiation with a mean irradiance above 6.1 x 10(10) W/cm(2), while non-incubated cells remained viable. Cells of both groups became necrotic when treated with an irradiance above 10.9 x 10(10) W/cm(2). The observed affected area of the cell layers was between 0.13 mm(2) and 1.10mm(2). Since the irradiation of non-incubated cells below the mean power density of 10.9 x 10(10) W/cm(2) induced no necrosis, apparently no thermal damage was induced in the cells and necrosis of the 5-ALA incubated cells can be ascribed to the photodynamic effect induced by two-photon excitation. The successful photodynamic treatment of a large area of a monolayer cell culture induced by two-photon excitation offers new perspectives for photodynamic treatment modalities. (c) 2007 Elsevier B. V. All rights reserved.
C1 Univ Munich, Laser Res Lab, Munich, Germany.
   Vilnius Univ, Laser Res Ctr, Vilnius, Lithuania.
   Vilnius Univ, Inst Immunol, Vilnius, Lithuania.
C3 University of Munich; Vilnius University; Vilnius University
RP Beck, TJ (通讯作者)，Univ Munich, Laser Res Lab, Marchioninistr 15, Munich, Germany.
EM tobias.beck@med.uni-muenchen.de
RI Rotomskis, Ricardas/C-8905-2014; Sroka, Ronald/I-2765-2013; Sroka,
   Ronald/AAN-1002-2020
OI Rotomskis, Ricardas/0000-0003-0825-4884
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NR 35
TC 19
Z9 19
U1 1
U2 24
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 1011-1344
EI 1873-2682
J9 J PHOTOCH PHOTOBIO B
JI J. Photochem. Photobiol. B-Biol.
PD JUN 26
PY 2007
VL 87
IS 3
BP 174
EP 182
DI 10.1016/j.jphotobiol.2007.03.008
PG 9
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 185WH
UT WOS:000247740600004
PM 17513121
DA 2022-11-30
ER

PT J
AU Rohrschneider, K
   Springer, C
   Bultmann, S
   Volcker, HE
AF Rohrschneider, K
   Springer, C
   Bultmann, S
   Volcker, HE
TI Microperimetry - Comparison between the Micro Perimeter 1 and scanning
   laser ophthalmoscope - Fundus perimetry
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; PHOTOCOAGULATION;
   FIXATION; DISEASE; VISION; EDEMA
AB PURPOSE: To compare microperimetry using the scanning laser ophthalmoscope (SLO, Rodenstock, Germany) and the recently introduced Micro Perimeter 1 (Nidek Technologies, Italy).
   DESIGN: Prospective comparative observational study.
   METHODS: Fundus perimetry with static threshold perimetry was performed using the SLO and the MP1 in 68 eyes of 40 consecutive patients with different retinal diseases for example, central serous chorioretinopathy, macular dystrophy, and age related macular degeneration. With both instruments, an automated 4-2-1 staircase strategy with Goldmann III stimuli and a comparable number of stimuli were applied. The depth and size of the detected scotomata as well as the location and stability of fixation were compared between both instruments.
   RESULTS: There was good concordance of results, with 75% (51 of 68 eyes) showing an equal defect. Whereas the MP I showed larger defects (depth and size) in 23.5% (16/68) of eyes studied than the SLO, the defects appeared larger with the SLO in 1 eye. Concerning fixation analysis, similar results were found for fixation stability with stable fixation in 47.1% (MP1: 32/68) and 48.5% (SLO: 33/68) and likewise for the location of fixation with foveal fixation in 54.4% (37/68) with the MP1 and the SLO. Whereas the average number of stimuli was similar for both instruments (MP1 56.8 +/- 16.1, SLO 62.9 +/- 17.0), examination time was prolonged with the MP1 (MP1: 11m35s +/- 3m47s, SLO: 10m29s +/- 3m23s). Throughout all examinations, fundus visualization with the SLO was superior to the MP1. 0
   CONCLUSIONS: For automated threshold microperimetry the MP1 provides results comparable to our SLO perimetry. Both instruments enable detection of sensitivity loss of the central visual field and an analysis of fixation behavior during microperimetry. Nevertheless, the MP1, with its automated real-time image alignment, facilitates examination. Additionally, the enlarged field allows testing in an area of 44 X 36 degrees instead of the 33 X 21 degree-area of the SLO. However, in comparison to our SLO-sofware, the current software of the MP1 requires improvements before exact measurements of defined retinal diseases are possible. (C) 2005 by Elsevier Inc. All rights reserved.
C1 Univ Heidelberg, Dept Ophthalmol, D-69120 Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg
RP Rohrschneider, K (通讯作者)，Univ Heidelberg, Dept Ophthalmol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
EM klaus_rohrschneider@med.uni-heidelberg.de
OI Rohrschneider, Klaus/0000-0003-1996-7935
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NR 14
TC 130
Z9 138
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JAN
PY 2005
VL 139
IS 1
BP 125
EP 134
DI 10.1016/j.ajo.2004.08.060
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 885XW
UT WOS:000226191700016
PM 15672526
DA 2022-11-30
ER

PT J
AU Merle, DA
   Provenzano, F
   Jarboui, MA
   Kilger, E
   Clark, SJ
   Deleidi, M
   Armento, A
   Ueffing, M
AF Merle, David A.
   Provenzano, Francesca
   Jarboui, Mohamed Ali
   Kilger, Ellen
   Clark, Simon J.
   Deleidi, Michela
   Armento, Angela
   Ueffing, Marius
TI mTOR Inhibition via Rapamycin Treatment Partially Reverts the Deficit in
   Energy Metabolism Caused by FH Loss in RPE Cells
SO ANTIOXIDANTS
LA English
DT Article
DE retinal pigment epithelium (RPE) cells; age-related macular degeneration
   (AMD); complement factor H (CFH; FH); mammalian target of rapamycin
   (mTOR); mitochondrial respiration; interactome; ubiquitin-proteasomal
   pathway
ID RETINAL-PIGMENT EPITHELIUM; UBIQUITIN-PROTEASOME PATHWAY; MACULAR
   DEGENERATION; GEOGRAPHIC ATROPHY; PHOSPHORYLATION; AUTOPHAGY;
   POLYMORPHISM; ASSOCIATION; DEGRADATION; IMPAIRMENT
AB Age-related macular degeneration (AMD) is a complex degenerative disease of the retina with multiple risk-modifying factors, including aging, genetics, and lifestyle choices. The combination of these factors leads to oxidative stress, inflammation, and metabolic failure in the retinal pigment epithelium (RPE) with subsequent degeneration of photoreceptors in the retina. The alternative complement pathway is tightly linked to AMD. In particular, the genetic variant in the complement factor H gene (CFH), which leads to the Y402H polymorphism in the factor H protein (FH), confers the second highest risk for the development and progression of AMD. Although the association between the FH Y402H variant and increased complement system activation is known, recent studies have uncovered novel FH functions not tied to this activity and highlighted functional relevance for intracellular FH. In our previous studies, we show that loss of CFH expression in RPE cells causes profound disturbances in cellular metabolism, increases the vulnerability towards oxidative stress, and modulates the activation of pro-inflammatory signaling pathways, most importantly the NF-kB pathway. Here, we silenced CFH in hTERT-RPE1 cells to investigate the mechanism by which intracellular FH regulates RPE cell homeostasis. We found that silencing of CFH results in hyperactivation of mTOR signaling along with decreased mitochondrial respiration and that mTOR inhibition via rapamycin can partially rescue these metabolic defects. To obtain mechanistic insight into the function of intracellular FH in hTERT-RPE1 cells, we analyzed the interactome of FH via immunoprecipitation followed by mass spectrometry-based analysis. We found that FH interacts with essential components of the ubiquitin-proteasomal pathway (UPS) as well as with factors associated with RB1/E2F signalling in a complement-pathway independent manner. Moreover, we found that FH silencing affects mRNA levels of the E3 Ubiquitin-Protein Ligase Parkin and PTEN induced putative kinase (Pink1), both of which are associated with UPS. As inhibition of mTORC1 was previously shown to result in increased overall protein degradation via UPS and as FH mRNA and protein levels were shown to be affected by inhibition of UPS, our data stress a potential regulatory link between endogenous FH activity and the UPS.
C1 [Merle, David A.; Jarboui, Mohamed Ali; Kilger, Ellen; Clark, Simon J.; Armento, Angela; Ueffing, Marius] Eberhard Karls Univ Tubingen, Dept Ophthalmol, Inst Ophthalm Res, D-72076 Tubingen, Germany.
   [Merle, David A.] Med Univ Graz, Dept Ophthalmol, A-8036 Graz, Austria.
   [Provenzano, Francesca; Deleidi, Michela; Ueffing, Marius] German Ctr Neurodegenerat Dis DZNE, D-72076 Tubingen, Germany.
   [Jarboui, Mohamed Ali] Eberhard Karls Univ Tuebingen, Inst Ophthalm Res, Core Facil Med Bioanalyt, D-72076 Tubingen, Germany.
   [Clark, Simon J.] Eberhard Karls Univ Tubingen, Univ Eye Clin, Dept Ophthalmol, D-72076 Tubingen, Germany.
   [Clark, Simon J.] Univ Manchester, Fac Biol Med & Hlth, Lydia Becker Inst Immunol & Inflammat, Manchester M13 9PT, Lancs, England.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Medical University of Graz; Eberhard Karls University of
   Tubingen; Eberhard Karls University Hospital; Helmholtz Association;
   German Center for Neurodegenerative Diseases (DZNE); Eberhard Karls
   University of Tubingen; Eberhard Karls University Hospital; Eberhard
   Karls University of Tubingen; Eberhard Karls University Hospital;
   University of Manchester
RP Armento, A; Ueffing, M (通讯作者)，Eberhard Karls Univ Tubingen, Dept Ophthalmol, Inst Ophthalm Res, D-72076 Tubingen, Germany.; Ueffing, M (通讯作者)，German Ctr Neurodegenerat Dis DZNE, D-72076 Tubingen, Germany.
EM david.merle@medunigraz.at; francesca.provenzano@dzne.de;
   mohamed-ali.jarboui@uni-tuebingen.de; ellen.kilger@uni-tuebingen.de;
   simon.clark@uni-tuebingen.de; michela.deleidi@dzne.de;
   angela.armento@uni-tuebingen.de; marius.ueffing@uni-tuebingen.de
RI Jarboui, Dr. Mohamed Ali/C-8496-2013
OI Jarboui, Dr. Mohamed Ali/0000-0002-5203-235X; Ueffing,
   Marius/0000-0003-2209-2113; Clark, Simon/0000-0001-8394-8355; Armento,
   Angela/0000-0002-6357-1500; Provenzano, Francesca/0000-0001-9171-564X
FU fortune-Programm [2640-0-0]; Kerstan Foundation; Helmut Ecker
   Foundation; Open Access Publishing Fund of University of Tubingen
FX A.A. is supported by the fortuene-Programm (project No. 2640-0-0). This
   work was supported by donations from Jutta Emilie Paula Henny Granier
   and the Kerstan Foundation to M.U. and the Helmut Ecker Foundation to
   S.J.C. We acknowledge support by Open Access Publishing Fund of
   University of Tuebingen.
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NR 76
TC 2
Z9 2
U1 2
U2 6
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD DEC
PY 2021
VL 10
IS 12
AR 1944
DI 10.3390/antiox10121944
PG 18
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Food Science &
   Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Food Science
   & Technology
GA XW7PR
UT WOS:000735806700001
PM 34943047
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Wooff, Y
   Cioanca, AV
   Chu-Tan, JA
   Aggio-Bruce, R
   Schumann, U
   Natoli, R
AF Wooff, Yvette
   Cioanca, Adrian V.
   Chu-Tan, Joshua A.
   Aggio-Bruce, Riemke
   Schumann, Ulrike
   Natoli, Riccardo
TI Small-Medium Extracellular Vesicles and Their miRNA Cargo in Retinal
   Health and Degeneration: Mediators of Homeostasis, and Vehicles for
   Targeted Gene Therapy
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Article
DE retina; neurodegeneration; extracellular vesicle; microRNA;
   immuno-modulation; gene therapy
ID EXOSOMAL MICRORNAS; INFLAMMATION; SECRETION; MICROGLIA; CANCER; CELLS;
   PHOTOBIOMODULATION; MICROVESICLES; BIOGENESIS; ACTIVATION
AB Photoreceptor cell death and inflammation are known to occur progressively in retinal degenerative diseases such as age-related macular degeneration (AMD). However, the molecular mechanisms underlying these biological processes are largely unknown. Extracellular vesicles (EV) are essential mediators of cell-to-cell communication with emerging roles in the modulation of immune responses. EVs, including exosomes, encapsulate and transfer microRNA (miRNA) to recipient cells and in this way can modulate the environment of recipient cells. Dysregulation of EVs however is correlated to a loss of cellular homeostasis and increased inflammation. In this work we investigated the role of isolated retinal small-medium sized EV (s-mEV) which includes exosomes in both the healthy and degenerating retina. Isolated s-mEV from normal retinas were characterized using dynamic light scattering, transmission electron microscopy and western blotting, and quantified across 5 days of photo-oxidative damage-induced degeneration using nanotracking analysis. Small RNAseq was used to characterize the miRNA cargo of retinal s-mEV isolated from healthy and damaged retinas. Finally, the effect of exosome inhibition on cell-to-cell miRNA transfer and immune modulation was conducted using systemic daily administration of exosome inhibitor GW4869 andin situhybridization of s-mEV-abundant miRNA, miR-124-3p. Electroretinography and immunohistochemistry was performed to assess functional and morphological changes to the retina as a result of GW4869-induced exosome depletion. Results demonstrated an inverse correlation between s-mEV concentration and photoreceptor survivability, with a decrease in s-mEV numbers following degeneration. Small RNAseq revealed that s-mEVs contained uniquely enriched miRNAs in comparison to in whole retinal tissue, however, there was no differential change in the s-mEV miRNAnome following photo-oxidative damage. Exosome inhibition via the use of GW4869 was also found to exacerbate retinal degeneration, with reduced retinal function and increased levels of inflammation and cell death demonstrated following photo-oxidative damage in exosome-inhibited mice. Further, GW4869-treated mice displayed impaired translocation of photoreceptor-derived miR-124-3p to the inner retina during damage. Taken together, we propose that retinal s-mEV and their miRNA cargo play an essential role in maintaining retinal homeostasis through immune-modulation, and have the potential to be used in targeted gene therapy for retinal degenerative diseases.
C1 [Wooff, Yvette; Cioanca, Adrian V.; Chu-Tan, Joshua A.; Aggio-Bruce, Riemke; Schumann, Ulrike; Natoli, Riccardo] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia.
   [Wooff, Yvette; Chu-Tan, Joshua A.; Aggio-Bruce, Riemke; Natoli, Riccardo] Australian Natl Univ, ANU Med Sch, Canberra, ACT, Australia.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University
RP Natoli, R (通讯作者)，Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia.; Natoli, R (通讯作者)，Australian Natl Univ, ANU Med Sch, Canberra, ACT, Australia.
EM riccardo.natoli@anu.edu.au
RI Aggio-Bruce, Riemke/AAX-4522-2020
OI Natoli, Riccardo/0000-0002-9350-0439; Cioanca,
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NR 117
TC 19
Z9 19
U1 1
U2 12
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD JUN 25
PY 2020
VL 14
AR 160
DI 10.3389/fncel.2020.00160
PG 26
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA MO8UZ
UT WOS:000551794800001
PM 32670023
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Ohlmann, A
   Scholz, M
   Koch, M
   Tamm, ER
AF Ohlmann, Andreas
   Scholz, Michael
   Koch, Marcus
   Tamm, Ernst R.
TI Epithelial-mesenchymal transition of the retinal pigment epithelium
   causes choriocapillaris atrophy
SO HISTOCHEMISTRY AND CELL BIOLOGY
LA English
DT Article
DE Age-related macula degeneration; Transforming growth factor-beta;
   Transgenic mice; Photoreceptor apoptosis; Angiogenesis
ID ENDOTHELIAL GROWTH-FACTOR; SMOOTH MUSCLE ACTIN; MACULAR DEGENERATION;
   TRANSGENIC MICE; VISUAL FUNCTION; FACTOR-BETA; CHOROIDAL
   NEOVASCULARIZATION; IN-VIVO; CELLS; EXPRESSION
AB Epithelial-to-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is commonly observed at sites of choroidal neovascularization in patients suffering from age-related macular degeneration. To learn in an experimental model how RPE EMT affects the biology of the choroidal vasculature, we studied transgenic mice (beta B1-TGF-beta 1) with ocular overexpression of transforming growth factor-beta 1 (TGF-beta 1). RPE EMT was detectable at postnatal day (P)1 and included marked structural and functional alterations such as loss of the outer blood-retina barrier and reduced mRNA expression of the RPE-characteristic molecules Rlbp1, Rpe65, Rbp1 and Vegfa. Moreover, vascular endothelial growth factor (VEGF) was not detectable by immunohistochemistry at the RPE/choroid interface, while RPE cells stained intensely for alpha-smooth muscle actin. The choriocapillaris, the characteristic choroidal capillary network adjacent to the RPE, developed normally and was not obviously changed in embryonic transgenic eyes but was absent at P1 indicating its atrophy. At around the same time, photoreceptors stopped to differentiate and photoreceptor apoptosis was abundant in the second week of life. Structural changes were also seen in the retinal vasculature of transgenic animals, which did not form intraretinal vessels, and the hyaloid vasculature, which did not regress. In addition, the amounts of retinal HIF-1 alpha and its mRNA were markedly reduced. We conclude that high amounts of active TGF-beta 1 in the mouse eye cause transdifferentiation of the RPE to a mesenchymal phenotype. The loss of epithelial differentiation leads to the diminished synthesis of RPE-characteristic molecules including that of VEGF. Lack of RPE-derived VEGF causes atrophy of the choriocapillaris, a scenario that disrupts photoreceptor differentiation and finally results in photoreceptor apoptosis. Lack of retinal vessel formation and of hyaloid vessel regression might be caused by the decrease in the metabolic requirements of the neuroretina leading to low amounts of retinal HIF-1 alpha. In summary, our data indicate that failure of RPE differentiation may well precede and cause atrophy of the choriocapillaris. In contrast, RPE EMT is not sufficient to cause choroidal neovascularization.
C1 [Ohlmann, Andreas; Koch, Marcus; Tamm, Ernst R.] Univ Regensburg, Inst Human Anat & Embryol, Univ Str 31, D-93053 Regensburg, Germany.
   [Scholz, Michael] Univ Erlangen Nurnberg, Inst Anat 2, Erlangen, Germany.
C3 University of Regensburg; University of Erlangen Nuremberg
RP Tamm, ER (通讯作者)，Univ Regensburg, Inst Human Anat & Embryol, Univ Str 31, D-93053 Regensburg, Germany.
EM Ernst.Tamm@ur.de
RI Tamm, Ernst/AAB-9772-2019
OI Tamm, Ernst/0000-0002-6679-8743; Ohlmann, Andreas/0000-0002-7101-9361;
   Scholz, Michael/0000-0001-8440-6785
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NR 70
TC 22
Z9 22
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0948-6143
EI 1432-119X
J9 HISTOCHEM CELL BIOL
JI Histochem. Cell Biol.
PD DEC
PY 2016
VL 146
IS 6
BP 769
EP 780
DI 10.1007/s00418-016-1461-4
PG 12
WC Cell Biology; Microscopy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Microscopy
GA EC0ST
UT WOS:000387811700013
PM 27372654
DA 2022-11-30
ER

PT J
AU Wang, JCC
   Wang, AK
   Gao, JY
   Cao, SJ
   Samad, I
   Zhang, DA
   Ritland, C
   Cui, JZ
   Matsubara, JA
AF Wang, Jay Ching Chieh
   Wang, Aikun
   Gao, Jiangyuan
   Cao, Sijia
   Samad, Idris
   Zhang, Dean
   Ritland, Carol
   Cui, Jing Z.
   Matsubara, Joanne Aiko
TI Technical Brief: Isolation of total DNA from postmortem human eye
   tissues and quality comparison between iris and retina
SO MOLECULAR VISION
LA English
DT Article
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; RISK; MELANIN; BLOOD; PCR
AB Background: Recent genomic technologies have propelled our understanding of the mechanisms underlying complex eye diseases such as age-related macular degeneration (AMD). Genotyping postmortem eye tissues for known single nucleotide polymorphisms (SNPs) associated with AMD may prove valuable, especially when combined with information obtained through other methods such as immunohistochemistry, western blot, enzyme-linked immunosorbent assay (ELISA), and proteomics. Initially intending to genotype postmortem eye tissues for AMD-related SNPs, our group became interested in isolating and comparing the quality of DNA from the iris and retina of postmortem donor eyes. Since there is no previously published protocol in the literature on this topic, we present a protocol suitable for isolating high-quality DNA from postmortem eye tissues for genomic studies.
   Methods: DNA from 33 retinal samples and 35 iris samples was extracted using the phenol-chloroform-isoamyl method from postmortem donor eye tissues. The quantity of DNA was measured with a spectrophotometer while the quality was checked using gel electrophoresis. The DNA samples were then amplified with PCR for the complement factor H (CFH) gene. The purified amplified products were then genotyped for the SNPs in the CFH gene.
   Results: Regarding concentration, the retina yielded 936 ng/mu l of DNA, while the iris yielded 78 ng/mu l of DNA. Retinal DNA was also purer than iris DNA (260/280=1.78 vs. 1.46, respectively), and produced superior PCR results. Retinal tissue yielded significantly more DNA than the iris tissue per mg of sample (21.7 ng/mu l/mg vs. 7.42 ng/mu l/mg). Retinal DNA can be readily amplified with PCR, while iris DNA can also be amplified by adding bovine serum albumin. Overall, retinal tissues yielded DNA of superior quality, quantity, and suitability for genotyping and genomic studies.
   Conclusions: The protocol presented here provides a clear and reliable method for isolating total DNA from postmortem eye tissues. Retinal tissue provides DNA of excellent quantity and quality for genotyping and downstream genomic studies. However, DNA isolated from iris tissues, and treated with bovine serum albumin, may also be a valuable source of DNA for genotyping and genomic studies.
C1 [Wang, Jay Ching Chieh; Wang, Aikun; Gao, Jiangyuan; Cao, Sijia; Samad, Idris; Zhang, Dean; Cui, Jing Z.; Matsubara, Joanne Aiko] Ophthalmol & Visual Sci Univ British Columbia Van, Vancouver, BC V5Z 3N9, Canada.
   [Ritland, Carol] Univ British Columbia, Dept Forest Sci, Vancouver, BC V6T 1W5, Canada.
C3 University of British Columbia
RP Matsubara, JA (通讯作者)，Ophthalmol & Visual Sci Univ British Columbia Van, Vancouver, BC V5Z 3N9, Canada.
EM jms@mail.ubc.ca
FU Canadian Institutes of Health Research [CIHR: MOP-97806, IAO77736]; BC
   Clinical Genomics Network
FX We thank Allyson Miscampbell and Hesther Yueh of UBC, Faculty of Forest
   Sciences and Orson Moritz of UBC, Department of Ophthalmology and Visual
   Sciences for their technical support and advice. The study was funded by
   the Canadian Institutes of Health Research (CIHR: MOP-97806, IAO77736)
   and the BC Clinical Genomics Network.
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NR 19
TC 4
Z9 4
U1 0
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD DEC 22
PY 2012
VL 18
IS 311
BP 3049
EP 3056
PG 8
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 062AI
UT WOS:000312891100001
PM 23288996
DA 2022-11-30
ER

PT J
AU Pemberton, TJ
   Mehta, NU
   Witonsky, D
   Di Rienzo, A
   Allayee, H
   Conti, DV
   Patel, PI
AF Pemberton, Trevor J.
   Mehta, Niyati U.
   Witonsky, David
   Di Rienzo, Anna
   Allayee, Hooman
   Conti, David V.
   Patel, Pragna I.
TI Prevalence of common disease-associated variants in Asian Indians
SO BMC GENETICS
LA English
DT Review
ID COMPLEMENT FACTOR-H; IMPAIRED GLUCOSE-TOLERANCE; PROSTATE-CANCER
   INCIDENCE; URBAN-RURAL EPIDEMIOLOGY; TYPE-2 DIABETES-MELLITUS;
   POPULATION GENOTYPE DATA; SUBUNIT 825T ALLELE; MACULAR DEGENERATION;
   BITTER-TASTE; RISK-FACTORS
AB Background: Asian Indians display a high prevalence of diseases linked to changes in diet and environment that have arisen as their lifestyle has become more westernized. Using 1200 genomewide polymorphisms in 432 individuals from 15 Indian language groups, we have recently shown that: (i) Indians constitute a distinct population-genetic cluster, and (ii) despite the geographic and linguistic diversity of the groups they exhibit a relatively low level of genetic heterogeneity.
   Results: We investigated the prevalence of common polymorphisms that have been associated with diseases, such as atherosclerosis (ALOX5), hypertension (CYP3A5, AGT, GNB3), diabetes (CAPN10, TCF7L2, PTPN22), prostate cancer (DG8S737, rs1447295), Hirschsprung disease (RET), and age-related macular degeneration (CFH, LOC387715). In addition, we examined polymorphisms associated with skin pigmentation (SLC24A5) and with the ability to taste phenylthiocarbamide (TAS2R38). All polymorphisms were studied in a cohort of 576 India-born Asian Indians sampled in the United States. This sample consisted of individuals whose mother tongue is one of 14 of the 22 "official" languages recognized in India as well as individuals whose mother tongue is Parsi, a cultural group that has resided in India for over 1000 years. Analysis of the data revealed that allele frequency differences between the different Indian language groups were small, and interestingly the variant alleles of ALOX5 g.8322G > A and g.50778G > A, and PTPN22 g.36677C > T were present only in a subset of the Indian language groups. Furthermore, a latitudinal cline was identified both for the allele frequencies of the SNPs associated with hypertension (CYP3A5, AGT, GNB3), as well as for those associated with the ability to taste phenylthiocarbamide (TAS2R38).
   Conclusion: Although caution is warranted due to the fact that this US-sampled Indian cohort may not represent a random sample from India, our results will hopefully assist in the design of future studies that investigate the genetic causes of these diseases in India. Our results also support the inclusion of the Indian population in disease-related genetic studies, as it exhibits unique genotype as well as phenotype characteristics that may yield new insights into the underlying causes of common diseases that are not available in other populations.
C1 [Pemberton, Trevor J.; Mehta, Niyati U.; Allayee, Hooman; Patel, Pragna I.] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA.
   [Allayee, Hooman; Conti, David V.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
   [Mehta, Niyati U.; Patel, Pragna I.] Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA USA.
   [Patel, Pragna I.] Univ So Calif, Keck Sch Med, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA.
   [Witonsky, David; Di Rienzo, Anna] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
C3 University of Southern California; University of Southern California;
   University of Southern California; University of Southern California;
   University of Chicago
RP Patel, PI (通讯作者)，Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA.
EM trevorp@usc.edu; niyatime@usc.edu; dwitonsk@genetics.uchicago.edu;
   dirienzo@genetics.bsd.uchicago.edu; hallayee@usc.edu; dconti@usc.edu;
   pragna@usc.edu
RI Pemberton, Trevor/F-9206-2018; Patel, Pragna/H-9129-2017
OI Patel, Pragna/0000-0003-3584-1072; Pemberton, Trevor/0000-0003-1224-1146
FU NATIONAL CANCER INSTITUTE [C06CA062528] Funding Source: NIH RePORTER;
   NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR010600, C06RR014514]
   Funding Source: NIH RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
   [R01HL079353] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   GENERAL MEDICAL SCIENCES [U01GM061393] Funding Source: NIH RePORTER; NCI
   NIH HHS [C06 CA062528, CA62528-01] Funding Source: Medline; NCRR NIH HHS
   [C06 RR014514, RR14514-01, RR10600-01] Funding Source: Medline; NHLBI
   NIH HHS [R01 HL079353] Funding Source: Medline; NIGMS NIH HHS [U01
   GM061393, GM61393] Funding Source: Medline
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NR 107
TC 34
Z9 35
U1 0
U2 10
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2156
J9 BMC GENET
JI BMC Genet.
PD FEB 4
PY 2008
VL 9
AR 13
DI 10.1186/1471-2156-9-13
PG 20
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 275CQ
UT WOS:000254049900001
PM 18248681
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Lee, PP
   Feldman, ZW
   Ostermann, J
   Brown, DS
   Sloan, FA
AF Lee, PP
   Feldman, ZW
   Ostermann, J
   Brown, DS
   Sloan, FA
TI Longitudinal rates of annual eye examinations of persons with diabetes
   and chronic eye diseases
SO OPHTHALMOLOGY
LA English
DT Article
ID RETINOPATHY; HEALTH; PREVALENCE; PEOPLE; CARE
AB Objective: To assess the rate of annual eye examinations over time among older Americans with diabetes and chronic eye diseases.
   Design: Longitudinal analysis of Medicare claims data.
   Participants: Random sample of Medicare beneficiaries aged 65 years or older.
   Methods: Beneficiaries were followed between 1991 and 1999, unless mortality or enrollment in a health maintenance organization for > 6 months in a given 12-month period intervened. All claims data (both physician and facility) during this time were analyzed for the presence of International Classification of Diseases 9 codes consistent with 1 of the 3 study conditions and the performance of eye examinations.
   Main Outcome Measures. Claims submitted by optometrists, ophthalmologists, or other providers of eye care for subjects with diabetes, glaucoma, or age-related macular degeneration (ARMD). Rates were calculated on the basis of a 15-month time window for annual examinations rather than for 12 months to allow for less than full compliance with the guidelines for various reasons (e.g., bad weather).
   Results: Among those with diabetes in this population, 50% to 60% had annual eye examinations in a 15-month period. Of those followed for at least 75 months after diagnosis, about three quarters had one or more 15-month gaps between visits. For subjects diagnosed with glaucoma, most visit rates were in the 70% to 90% range per 15-month period. The percentage of subjects with at least one 15-month period with no visits was considerably lower than for diabetes. The patterns for those with ARMD were in between those for diabetes and glaucoma. Over a nine-year period, only slightly over half of persons with at least one of the study conditions complied with practice guidelines.
   Conclusions: Annual eye examinations for persons diagnosed with diabetes, glaucoma, and ARMD are important for detecting potentially treatable vision loss among those already diagnosed with these conditions. Currently, actual rates of eye examinations for persons diagnosed with the study conditions fall far short of recommended rates. As such, approaches to enhancing longitudinal follow-up of those already in the eye care system are needed. (C) 2003 by the American Academy of Ophthalmology.
C1 Duke Univ, Ctr Hlth Policy Law & Management, Durham, NC 27708 USA.
   Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC 27708 USA.
   Duke Univ, Dept Econ, Durham, NC 27708 USA.
C3 Duke University; Duke University; Duke University
RP Sloan, FA (通讯作者)，Duke Univ, Ctr Hlth Policy Law & Management, Box 90523, Durham, NC 27708 USA.
RI Ostermann, Jan/GQB-4743-2022; Brown, Derek S/J-3035-2013
OI Brown, Derek S/0000-0001-9908-9882; Ostermann, Jan/0000-0002-8236-9500;
   Lee, Paul/0000-0002-3338-136X
FU NATIONAL INSTITUTE ON AGING [R01AG017473] Funding Source: NIH RePORTER;
   NIA NIH HHS [1R01 AG 17473] Funding Source: Medline
CR *AM AC OPHTH, 1998, PREF PRACT PATT DIAB
   *AM AC OPHTH, 2000, PREF PRACT PATT PRIM
   *AM AC OPHTH, 2001, PREF PRACT PATT AG R
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NR 18
TC 123
Z9 125
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD OCT
PY 2003
VL 110
IS 10
BP 1952
EP 1959
DI 10.1016/S0161-6420(03)00817-0
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 726TF
UT WOS:000185615400016
PM 14522771
DA 2022-11-30
ER

PT J
AU Moshfeghi, DM
   Kaiser, PK
   Grossniklaus, HE
   Sternberg, P
   Sears, JE
   Johnson, MW
   Ratliff, N
   Branco, A
   Blumenkranz, MS
   Lewis, H
AF Moshfeghi, DM
   Kaiser, PK
   Grossniklaus, HE
   Sternberg, P
   Sears, JE
   Johnson, MW
   Ratliff, N
   Branco, A
   Blumenkranz, MS
   Lewis, H
TI Clinicopathologic study after submacular removal of choroidal
   neovascular membranes treated with verteporfin ocular photodynamic
   therapy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; NORMAL RETINA
AB PURPOSE: To report the clinicopathologic findings after submacular removal of choroidal neovascular membranes (CNV) treated with verteporfin ocular photodynamic therapy.
   DESIGN: Interventional case series.
   METHODS: Retrospective review of eight eyes of eight patients who underwent submacular surgery for CNV after having previously received verteporfin ocular photodynamic therapy for presumed ocular histoplasmosis (one patient), age,related macular degeneration ([AMD] three patients) pathologic myopia (two patients), punctate inner choroiditis (one patient), and idiopathic CNV (one patient). All cases had undergone ocular photodynamic therapy with verteporfin using standard protocols. Six of eight patients suffered a submacular hemorrhage after ocular photodynamic therapy, and two of eight patients refused further ocular photodynamic therapy. All patients subsequently had submacular surgery with removal of the CNV. One membrane was routinely processed, sectioned, and stained with hematoxylin and eosin. Five membranes were stained with toluidine blue for light microscopic examination. Semithin (1.0 mum) sections were cut and stained with uranyl acetate-lead citrate for transmission electron microscopy.
   RESULTS: Choroidal neovascular membranes were removed at 3 days (presumed ocular histoplasmosis), 29 days (punctate inner choroiditis), 63 days (AMD, pathologic myopia), 66 days (AMD), 107 days (pathologic myopia), 116 days (AMD), and 152 days (idiopathic) after verteporfin ocular photodynamic therapy. Histopathologic and ultrastructural examination showed areas of vascular occlusion at 3 days that were not seen at later time points. All specimens had patent CNV. There were signs of vascular damage with extravasated erythrocytes and fibrin, pigment clumping in cells, and inflammatory cells in all but the 3 day specimen.
   CONCLUSIONS: This case series presents data only from patients who refused repeat treatment with ocular photodynamic therapy or who developed submacular hemorrhage after initial photodynamic therapy. Histopathologic evaluation of CNV 3 days after verteporfin ocular photodynamic therapy showed partial vascular occlusion that was not present in later specimens. These later specimens demonstrated evidence of vascular damage. Verteporfin ocular photodynamic therapy does not appear to lead to permanent and complete occlusion of the CNV. Thus, treatments that lead to permanent closure of CNV without damage to the retinal pigment epithelium and sensory retina are still needed. (C) 2003 by Elsevier Science Inc. All rights reserved.
C1 Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
   Emory Univ, Dept Ophthalmol, Sch Med, Atlanta, GA 30322 USA.
   Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Sch Med, Ann Arbor, MI 48109 USA.
   Cleveland Clin Fdn, Dept Pathol, Cleveland, OH 44195 USA.
   Stanford Univ, Sch Med, Dept Ophthalmol, Stanford, CA 94305 USA.
C3 Cleveland Clinic Foundation; Emory University; University of Michigan
   System; University of Michigan; Cleveland Clinic Foundation; Stanford
   University
RP Kaiser, PK (通讯作者)，Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave,Desk i-3, Cleveland, OH 44195 USA.
EM pkkaiser@aol.com
OI Kaiser, Peter/0000-0001-5126-045X; Moshfeghi, Darius
   Mohammad/0000-0003-2254-292X; Johnson, Mark W/0000-0001-9720-8761
CR Arnold J, 2001, OPHTHALMOLOGY, V108, P841
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NR 23
TC 53
Z9 60
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD MAR
PY 2003
VL 135
IS 3
BP 343
EP 350
AR PII S0002-9394(02)01936-0
DI 10.1016/S0002-9394(02)01936-0
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 650HT
UT WOS:000181258100012
PM 12614752
DA 2022-11-30
ER

PT J
AU Allyn, MM
   Luo, RH
   Hellwarth, EB
   Swindle-Reilly, KE
AF Allyn, Megan M.
   Luo, Richard H.
   Hellwarth, Elle B.
   Swindle-Reilly, Katelyn E.
TI Considerations for Polymers Used in Ocular Drug Delivery
SO FRONTIERS IN MEDICINE
LA English
DT Review
DE drug delivery; polymer; hydrogel; ophthalmic delivery; ocular implants;
   controlled release; ocular biomaterials
ID IN-VITRO EVALUATION; CONTACT-LENSES; SUPRACHOROIDAL SPACE;
   HYALURONIC-ACID; CONTROLLED-RELEASE; DRY-EYE; POLY(ACRYLIC
   ACID-CO-N-ISOPROPYLACRYLAMIDE); TRIAMCINOLONE ACETONIDE; SUSTAINED
   DELIVERY; POSTERIOR SEGMENT
AB PurposeAge-related eye diseases are becoming more prevalent. A notable increase has been seen in the most common causes including glaucoma, age-related macular degeneration (AMD), and cataract. Current clinical treatments vary from tissue replacement with polymers to topical eye drops and intravitreal injections. Research and development efforts have increased using polymers for sustained release to the eye to overcome treatment challenges, showing promise in improving drug release and delivery, patient experience, and treatment compliance. Polymers provide unique properties that allow for specific engineered devices to provide improved treatment options. Recent work has shown the utilization of synthetic and biopolymer derived biomaterials in various forms, with this review containing a focus on polymers Food and Drug Administration (FDA) approved for ocular use. MethodsThis provides an overview of some prevalent synthetic polymers and biopolymers used in ocular delivery and their benefits, brief discussion of the various types and synthesis methods used, and administration techniques. Polymers approved by the FDA for different applications in the eye are listed and compared to new polymers being explored in the literature. This article summarizes research findings using polymers for ocular drug delivery from various stages: laboratory, preclinical studies, clinical trials, and currently approved. This review also focuses on some of the challenges to bringing these new innovations to the clinic, including limited selection of approved polymers. ResultsPolymers help improve drug delivery by increasing solubility, controlling pharmacokinetics, and extending release. Several polymer classes including synthetic, biopolymer, and combinations were discussed along with the benefits and challenges of each class. The ways both polymer synthesis and processing techniques can influence drug release in the eye were discussed. ConclusionThe use of biomaterials, specifically polymers, is a well-studied field for drug delivery, and polymers have been used as implants in the eye for over 75 years. Promising new ocular drug delivery systems are emerging using polymers an innovative option for treating ocular diseases because of their tunable properties. This review touches on important considerations and challenges of using polymers for sustained ocular drug delivery with the goal translating research to the clinic.
C1 [Allyn, Megan M.; Swindle-Reilly, Katelyn E.] Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA.
   [Luo, Richard H.; Hellwarth, Elle B.; Swindle-Reilly, Katelyn E.] Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA.
   [Swindle-Reilly, Katelyn E.] Ohio State Univ, Dept Ophthalmol & Visual Sci, Columbus, OH 43210 USA.
C3 University System of Ohio; Ohio State University; University System of
   Ohio; Ohio State University; University System of Ohio; Ohio State
   University
RP Swindle-Reilly, KE (通讯作者)，Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA.; Swindle-Reilly, KE (通讯作者)，Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA.; Swindle-Reilly, KE (通讯作者)，Ohio State Univ, Dept Ophthalmol & Visual Sci, Columbus, OH 43210 USA.
EM reilly.198@osu.edu
OI Hellwarth, Elle/0000-0003-4498-7700
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NR 250
TC 7
Z9 7
U1 10
U2 27
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 2296-858X
J9 FRONT MED-LAUSANNE
JI Front. Med.
PD JAN 28
PY 2022
VL 8
AR 787644
DI 10.3389/fmed.2021.787644
PG 25
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA ZG8YI
UT WOS:000760537900001
PM 35155469
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Shen, Y
   Xie, C
   Gu, YS
   Li, XY
   Tong, JP
AF Shen, Ye
   Xie, Chen
   Gu, Yangshun
   Li, Xiuyi
   Tong, Jianping
TI Illumination from light-emitting diodes (LEDs) disrupts pathological
   cytokines expression and activates relevant signal pathways in primary
   human retinal pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Light-emitting diodes; RPE cells; AMD; MAPK; NF-kappa B; Pathological
   cytokine; Oxidative stress
ID NF-KAPPA-B; MACULAR DEGENERATION; SUNLIGHT EXPOSURE; AQUEOUS-HUMOR;
   AMYLOID-BETA; INFLAMMASOME ACTIVATION; NLRP3 INFLAMMASOME; OXIDATIVE
   STRESS; INTRAOCULAR-LENS; INTERLEUKIN-8
AB Age-related macular degeneration (AMD) is the leading cause of blindness in the aged people. The latest systemic review of epidemiological investigations revealed that excessive light exposure increases the risk of AMD. With the drastically increasing use of high-energy light-emitting diodes (LEDs) light in our domestic environment nowadays, it is supposed to pose a potential oxidative threat to ocular health. Retinal pigment epithelium (RPE) is the major ocular source of pathological cytokines, which regulate local inflammation and angiogenesis. We hypothesized that high-energy LED light might disrupt the pathological cytokine expression of retinal pigment epithelium (RPE), contributing to the pathogenesis of AMD. Primary human RPE cells were isolated from eyecups of normal eye donors and seeded into plate wells for growing to confluence. Two widely used multichromatic white light-emitting diodes (LEDs) with correlated color temperatures (CCTs) of 2954 and 7378 K were used in this experiment. The confluent primary RPE cells were under white LEDs light exposure until 24 h. VEGF-A, IL-6, IL-8 and MCP-1 proteins and mRNAs were measured using an ELISA kit and RT-PCR, respectively. Activation of mitogen-activated protein kinases (MAPKs), Akt, Janus kinase (JAK)2 and Nuclear factor (NF)-kappa B signal pathways after LEDs illumination were evaluated by western blotting analysis. The level of reactive oxygen species (ROS) using chloromethyl- 2',7'-dichlorodihydrofluorescein diacetate. Inhibitors of relevant signal pathways and anti-oxidants were added to the primary RPE cells before LEDs illumination to evaluate their biological functions. We found that 7378 K light, but not 2954 K upregulated the VEGF-A, IL-6, IL-8 and downregulated MCP-1 proteins and mRNAs levels in a time-dependent manner. In parallel, initial activation of MAPKs and NF-kappa B signal pathways were also observed after 7378 K light exposure. Mechanistically, antioxidants for eliminating reactive oxygen species (ROS) and targeted inhibitors of MAPKs and NF-kappa B significantly blocked 7378 K light-induced changes of specific cytokines, respectively. Our findings suggest that 7378 K light, not 2954 K induced upregulation of VEGF-A, IL-6, IL-8 and downregulation of MCP-1 via ROS accumulation, activating MAPKs and NF-kappa B signal pathways. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Shen, Ye; Xie, Chen; Gu, Yangshun; Li, Xiuyi; Tong, Jianping] Zhejiang Univ, Coll Med, Affiliated Hosp 1, Dept Ophthalmol, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China.
   [Xie, Chen] Zhejiang Univ, Sch Med, Affiliate Hosp 1, Clin Res Ctr, Hangzhou 310003, Zhejiang, Peoples R China.
C3 Zhejiang University; Zhejiang University
RP Tong, JP (通讯作者)，Zhejiang Univ, Coll Med, Affiliated Hosp 1, Dept Ophthalmol, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China.
EM tongjp2000@hotmail.com
FU Natural Science Foundation of Zhejiang Province, China [LY13H120001];
   Key Social Development Projects, Science Technology Department of
   Zhejiang Province, China [2013C03048-2]; Major Science and Technology
   Programs
FX This work was supported in part by the Natural Science Foundation of
   Zhejiang Province, China (code: LY13H120001) and Major Science and
   Technology Programs and Key Social Development Projects, Science
   Technology Department of Zhejiang Province, China (code: 2013C03048-2).
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NR 64
TC 21
Z9 21
U1 0
U2 19
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD APR
PY 2016
VL 145
BP 456
EP 467
DI 10.1016/j.exer.2015.09.016
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DL1DL
UT WOS:000375372300052
PM 26432918
DA 2022-11-30
ER

PT J
AU Park, UC
   Shin, JY
   McCarthy, LC
   Kim, SJ
   Park, JH
   Chung, H
   Yu, HG
AF Park, Un Chul
   Shin, Joo Young
   McCarthy, Linda C.
   Kim, Sang Jin
   Park, Jung Hyun
   Chung, Hum
   Yu, Hyeong Gon
TI Pharmacogenetic associations with long-term response to anti-vascular
   endothelial growth factor treatment in neovascular AMD patients
SO MOLECULAR VISION
LA English
DT Article
ID COMPLEMENT-FACTOR-H; GENOME-WIDE ASSOCIATION; TREATMENTS TRIALS CATT;
   MACULAR DEGENERATION; INTRAVITREAL RANIBIZUMAB; CHINESE POPULATION; GENE
   POLYMORPHISM; FACTOR THERAPY; BEVACIZUMAB; VEGFA
AB Purpose: To investigate the pharmacogenetic associations between the genetic risk variants of age-related macular degeneration (AMD) and long-term outcome after intravitreal anti-vascular endothelial growth factor (VEGF) treatment in Korean neovascular AMD patients.
   Methods: This prospective study included 394 treatment-naive patients (394 eyes) that underwent intravitreal anti-VEGF treatment for neovascular AMD for at least 12 months. Patients were genotyped for 17 single nucleotide polymorphisms within 13 AMD-relevant genes. Initially, patients underwent three monthly injections of intravitreal ranibizumab and were retreated as needed with ranibizumab or bevacizumab. For each candidate polymorphism, genotypic associations with treatment outcome measures at months 12 and 24, including mean change in best-corrected visual acuity (BCVA) from baseline, visual gain of >= 15 letters, mean change in central subfield macular thickness (CSMT) from baseline on spectral domain optical coherence tomography (OCT), presence of fluid on OCT, and mean number of injections, were investigated using logistic or linear regression models with adjustment for non-genetic covariates.
   Results: At month 24, BCVA improved by 4.5 +/- 22.5 letters and CSMT decreased by 69.4 +/- 112.6 mu m from baseline. Regression analysis with Bonferroni correction showed that the TT genotype for VEGFA rs3025039 was associated with a significantly higher chance of a visual gain of >= 15 letters at month 24 than other genotypes (odds ratio, 4.57; 95% confidence interval, 1.89-11.1; corrected p = 0.0434). As for tomographic outcome, the minor allele homozygotes for ARMS2 rs10490924 and HTRA1 rs1100638 (GG genotype for both) were associated with a larger CSMT reduction at month 12 than other genotypes, with borderline significance after Bonferroni correction (118.6 +/- 132.7 mu m versus 62.7 +/- 89.7 mu m, corrected p = 0.0656 for rs10490924; 115.7 +/- 131.7 mu m versus 63.6 +/- 89.8 mu m, corrected p = 0.0528 for rs11200638). No polymorphism showed a significant association with the number of injections.
   Conclusions: In this Korean neovascular AMD cohort, treatment outcome after anti-VEGF was found to differ by the genotypes of VEGFA rs3025039, ARMS2 rs10490924, and HTRA1 rs11200638. Given more evidence of pharmacogenetic associations with the anti-VEGF agent, individualized therapeutic approaches based on genetic background could lead to optimal treatment in neovascular AMD.
C1 [Park, Un Chul; Shin, Joo Young; Kim, Sang Jin; Park, Jung Hyun; Chung, Hum; Yu, Hyeong Gon] Seoul Natl Univ, Coll Med, Dept Ophthalmol, Seoul 110799, South Korea.
   [Park, Un Chul] Natl Med Ctr, Dept Ophthalmol, Seoul, South Korea.
   [McCarthy, Linda C.] GlaxoSmithKline Med Res Ctr, Stevenage, Herts, England.
   [Kim, Sang Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul, South Korea.
   [Park, Jung Hyun] Inje Univ, Seoul Paik Hosp, Dept Ophthalmol, Seoul, South Korea.
   [Yu, Hyeong Gon] Seoul Natl Univ, Med Res Ctr, Sensory Organs Inst, Seoul 110799, South Korea.
C3 Seoul National University (SNU); National Medical Center - Korea;
   GlaxoSmithKline; Sungkyunkwan University (SKKU); Samsung Medical Center;
   Inje University; Seoul National University (SNU)
RP Yu, HG (通讯作者)，Seoul Natl Univ, Coll Med, Dept Ophthalmol, 103 Daehak Ro, Seoul 110799, South Korea.
EM hgonyu@snu.ac.kr
OI Shin, Joo Young/0000-0001-5062-6392; Yu, Hyeong Gon/0000-0002-1795-202X
FU GlaxoSmithKline Medicines Research Centre; SNUH Research Fund
   [04-2011-1160]
FX lThe authors thank Dr. Jong Eun Lee and Sujin Kim for their technical
   support of genetic analyses. This study was funded by GlaxoSmithKline
   Medicines Research Centre and supported in part by grant No.
   04-2011-1160 from the SNUH Research Fund.
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NR 48
TC 26
Z9 26
U1 0
U2 1
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD DEC 19
PY 2014
VL 20
BP 1680
EP 1694
PG 15
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA CG0WO
UT WOS:000352993900001
PM 25558172
DA 2022-11-30
ER

PT J
AU Umeda, S
   Ayyagari, R
   Allikmets, R
   Suzuki, MT
   Karoukis, AJ
   Ambasudhan, R
   Zernant, J
   Okamoto, H
   Ono, F
   Terao, K
   Mizota, A
   Yoshikawa, Y
   Tanaka, Y
   Iwata, T
AF Umeda, S
   Ayyagari, R
   Allikmets, R
   Suzuki, MT
   Karoukis, AJ
   Ambasudhan, R
   Zernant, J
   Okamoto, H
   Ono, F
   Terao, K
   Mizota, A
   Yoshikawa, Y
   Tanaka, Y
   Iwata, T
TI Early-onset macular degeneration with drusen in a cynomolgus monkey
   (Macaca fascicularis) pedigree: exclusion of 13 candidate genes and loci
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
AB PURPOSE. To describe hereditary macular degeneration observed in the cynomolgus monkey ( Macaca fascicularis), which shares phenotypic features with age- related macular degeneration in humans, and to test the involvement of candidate gene loci by mutation screening and linkage analysis.
   METHODS. Ophthalmic examinations with fundus photography, fluorescein angiography ( FA), indocyanine green angiography ( IA), electroretinography ( ERG), and histologic studies were performed on both affected and unaffected monkeys in the pedigree. The monkey orthologues of the human ABCA4, VMD2, EFEMP1, TIMP3, and ELOVL4 genes were cloned and screened for mutations by single- strand conformation polymorphism ( SSCP) analysis or denaturing high- performance liquid chromatography ( DHPLC) and direct sequencing in six affected and five unaffected monkeys from the pedigree and in six unrelated, unaffected monkeys. Subsequently, 13 human macular degeneration loci including these five genes were analyzed to test for linkage with the disease. Nineteen affected and seven unaffected monkeys in the pedigree were analyzed by using human microsatellite markers linked to the 13 loci.
   RESULTS. Yellowish white spots were observed in the macula and fovea centralis, and in some cases the spots scattered to the peripheral retina along the blood vessels. FA showed hyperfluorescence corresponding to the dots except in the foveola. No anomalies were found by IA and ERG. Histologic studies demonstrated that the spots were drusen. Mutation analysis of the ABCA4, VMD2, EFEMP1, TIMP3, and ELOVL4 genes identified a few sequence variants, but none of them segregated with the disease. Linkage analysis with markers linked to these five genes and an additional eight human macular degeneration loci failed to establish linkage. Haplotype analysis excluded the involvement of the 13 candidate loci for harboring the gene associated with macular degeneration in the monkeys.
   CONCLUSIONS. Significant homology was identified between monkey and human orthologues of the five macular degeneration genes. Thirteen loci associated with macular degeneration in humans or harboring macular degeneration genes were excluded as causal of early- onset macular degeneration in the monkeys. It is likely that none of these loci, but rather a novel gene, is involved in causing the observed phenotype in this monkey pedigree.
C1 Natl Hosp Org Tokyo Med Ctr, Natl Inst Sensory Organs, Meguro Ku, Tokyo 1528902, Japan.
   Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biomed Sci, Tokyo, Japan.
   Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol, Ann Arbor, MI 48105 USA.
   Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
   Columbia Univ, Dept Pathol, New York, NY USA.
   Corp Prod & Res Lab Primates, Ibaraki, Japan.
   Natl Inst Infect Dis, Tsukuba Primate Ctr Med Sci, Ibaraki, Japan.
   Juntendo Univ, Urayasu Hosp, Dept Ophthalmol, Chiba, Japan.
C3 University of Tokyo; University of Michigan System; University of
   Michigan; Columbia University; Columbia University; National Institute
   of Infectious Diseases (NIID); Juntendo University
RP Iwata, T (通讯作者)，Natl Hosp Org Tokyo Med Ctr, Natl Inst Sensory Organs, Meguro Ku, 2-5-1 Higashigaoka, Tokyo 1528902, Japan.
EM iwatatakeshi@kankakuki.go.jp
RI Allikmets, Rando/ABD-4533-2021
FU NEI NIH HHS [EY13198, EY13435, EY07003] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [R01EY013435, R01EY013198] Funding Source: NIH
   RePORTER
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NR 45
TC 31
Z9 34
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2005
VL 46
IS 2
BP 683
EP 691
DI 10.1167/iovs.04-1031
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 890WP
UT WOS:000226542100040
PM 15671300
DA 2022-11-30
ER

PT J
AU Vorum, H
   Olesen, TK
   Zinck, J
   Hedegaard, MS
AF Vorum, Henrik
   Olesen, Thorbjorn Kruse
   Zinck, Jette
   Hedegaard, Morten Storling
TI Real world evidence of use of anti-VEGF therapy in Denmark
SO CURRENT MEDICAL RESEARCH AND OPINION
LA English
DT Article
DE Aflibercept; Macular edema; Observational study; Ranibizumab;
   Registries; Retinal vein occlusion; Wet macular degeneration
ID DIABETIC MACULAR EDEMA; INTRAVITREAL AFLIBERCEPT INJECTION; 2.0 MG
   RANIBIZUMAB; QUALITY-OF-LIFE; TREATMENT PATTERNS; EXTEND REGIMEN;
   VISUAL-ACUITY; DEGENERATION; OUTCOMES; SAFETY
AB Objective: This study evaluates real-world evidence regarding the frequency of anti-vascular-endothelial-growth-factor (VEGF) injections during the first year of therapy of treatment-naive patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME) and retinal vein occlusion (RVO) from the Danish National Patient Registry. There was a switch in anti-VEGF treatment for naive nAMD patients during the study period, following the introduction of aflibercept, which was expected to reduce the injection frequency relative to ranibizumab due to a perception of prolonged treatment duration of aflibercept.
   Methods: All treatment-naive nAMD, DME or RVO patients who received an intravitreal injection in Denmark from 1 January 2012 to 31 July 2015 were eligible for inclusion. Patients were required to have been treated for at least one year and, for nAMD, to have received at least three injections during the first four months of treatment. Patients were allocated to half-year groupings (2012/1 to 2014/1) based on registration of their first intravitreal injection. Injection frequency during the first year of treatment was calculated for each group and t-tests investigated whether injection frequencies changed over time.
   Results: In treatment naive nAMD patients (n=500), the mean (SD) number of anti-VEGF injections increased significantly from 6.04 (1.71) in 2012/1 to 6.73 (1.62) in 2014/1 (p=.001; 2012/1 and 2012/2 vs. 2014/1) across all treatments. A similar trend was found for DME patients (n=76) from 2012/1 to 2014/1 and RVO patients (n=82) from 2012/2 to 2014/1, with mean injection frequencies increasing significantly from 5.14 (2.29) to 5.93 (1.98) (p=.007), and from 4.83 (1.21) to 6.08 (1.55) (p=.024), respectively. Post hoc sensitivity analysis also found a significant increase in injection frequency in nAMD patients who did not receive a loading phase (4.55 in 2012/1 and 5.05 in 2014/1; p=.006; n=616).
   Conclusions: In contrast to the decrease in injection frequency predicted with a switch to aflibercept treatment for nAMD, our study showed that injection frequencies increased significantly from 2012 to 2014 in patients initiating therapy across the three diseases.
C1 [Vorum, Henrik] Aalborg Univ Hosp, Aalborg, Denmark.
   [Vorum, Henrik] Aalborg Univ, Aalborg, Denmark.
   [Olesen, Thorbjorn Kruse; Zinck, Jette] DLi Market Intelligence, Copenhagen, Denmark.
   [Hedegaard, Morten Storling] Novartis Healthcare, Copenhagen, Denmark.
C3 Aalborg University; Aalborg University Hospital; Aalborg University
RP Vorum, H (通讯作者)，Aalborg Univ Hosp, Dept Ophthalmol, Aalborg, Denmark.; Vorum, H (通讯作者)，Aalborg Univ, Dept Clin Med, Aalborg, Denmark.
EM henrik.vorum@rn.dk
FU Novartis Healthcare
FX This study was funded by Novartis Healthcare.
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NR 45
TC 19
Z9 21
U1 0
U2 3
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0300-7995
EI 1473-4877
J9 CURR MED RES OPIN
JI Curr. Med. Res. Opin.
PD DEC
PY 2016
VL 32
IS 12
BP 1943
EP 1950
DI 10.1080/03007995.2016.1221803
PG 8
WC Medicine, General & Internal; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Research & Experimental Medicine
GA ED6JB
UT WOS:000388960800004
PM 27494692
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Chintalapudi, SR
   Wang, XF
   Li, HL
   Lau, YHC
   Williams, RW
   Jablonski, MM
AF Chintalapudi, Sumana R.
   Wang, XiaoFei
   Li, Huiling
   Lau, Yin H. Chan
   Williams, Robert W.
   Jablonski, Monica M.
TI Genetic and immunohistochemical analysis of HSPA5 in mouse and human
   retinas
SO MOLECULAR VISION
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; HEPARAN-SULFATE; INTERPHOTORECEPTOR
   MATRIX; GRP78; BXD; PHOTORECEPTORS; LOCALIZATION; ACTIVATION;
   EXPRESSION; MEMBRANE
AB Purpose: Photoreceptor degenerative diseases are among the leading causes of vision loss. Although the causative genetic mutations are often known, mechanisms leading to photoreceptor degeneration remain poorly defined. We have previously demonstrated that the photoreceptor membrane-associated protein XAP-1 antigen is a product of the HSPA5 gene. In this study, we used systems genetic methods, statistical modeling, and immunostaining to identify and analyze candidate genes that modulate Hspa5 expression in the retina.
   Methods: Quantitative trait locus (QTL) mapping was used to map the genomic region that regulates Hspa5 in the cross between C57BL/6J X DBA/2J mice (BXD) genetic reference panel. The stepwise refinement of candidate genes was based on expression QTL mapping, gene expression correlation analyses (direct and partial), and analysis of regional sequence variants. The subcellular localization of candidate proteins and HSPA5 in mouse and human retinas was evaluated by immunohistochemistry. Differences in the localization of extracellular HSPA5 were assessed between healthy human donor and atrophic age-related macular degeneration (AMD) donor eyes.
   Results: In the eyes of healthy mice, extracellular HSPA5 was confined to the area around the cone photoreceptor outer segments. Mapping variation in Hspa5 mRNA expression levels in the retina revealed a statistically significant trans-acting expression QTL (eQTL) on Chromosome 2 (Chr 2) and a suggestive locus on Chr 15. Sulf2 on Chr 2 was the strongest candidate gene based on partial correlation analysis, Pearson correlation with Hspa5, expression levels in the retina, a missense variant in exon 14, and its reported function in the extracellular matrix and interphotoreceptor matrix. SULF2 is localized to the rod and cone photoreceptors in both human and mouse retinas. In human retinas with no pathology, extracellular HSPA5 was localized around many cones within the macular area. In contrast, fewer HSPA5-immunopositive cones were observed in the retinas from AMD donors.
   Conclusions: We identified Sulf2 as a candidate gene modulating the Hspa5 expression in the retina. The preferential loss of HSPA5 in the interphotoreceptor matrix around cone photoreceptors in atrophic AMD retinas opens up new avenues for exploring the changes in interphotoreceptor matrix (IPM) that are associated with macular disease.
C1 [Chintalapudi, Sumana R.; Wang, XiaoFei; Li, Huiling; Lau, Yin H. Chan; Jablonski, Monica M.] Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, Hamilton Eye Inst, Memphis, TN 38163 USA.
   [Chintalapudi, Sumana R.; Williams, Robert W.; Jablonski, Monica M.] Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA.
   [Li, Huiling] Cent South Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha, Hunan, Peoples R China.
   [Williams, Robert W.] Univ Tennessee, Ctr Hlth Sci, Dept Genet Genom & Informat, Memphis, TN 38163 USA.
   [Jablonski, Monica M.] Univ Tennessee, Ctr Hlth Sci, Dept Pharmaceut Sci, Memphis, TN 38163 USA.
C3 University of Tennessee System; University of Tennessee Health Science
   Center; University of Tennessee System; University of Tennessee Health
   Science Center; Central South University; University of Tennessee
   System; University of Tennessee Health Science Center; University of
   Tennessee System; University of Tennessee Health Science Center
RP Jablonski, MM (通讯作者)，Univ Tennessee, Ctr Hlth Sci, Hamilton Eye Inst, 930 Madison Ave,Suite 758, Memphis, TN 38163 USA.
EM mjablonski@uthsc.edu
RI Chintalapudi, Sumana Rameshbabu/AAJ-4008-2021; Williams, Robert
   W./H-8789-2016
OI Chintalapudi, Sumana Rameshbabu/0000-0003-1079-0950; Williams, Robert
   W./0000-0001-8924-4447
FU NEI [EY021200, P30EY013080]; Research to Prevent Blindness, Inc.;
   NATIONAL EYE INSTITUTE [P30EY013080, R01EY021200] Funding Source: NIH
   RePORTER
FX The authors acknowledge the financial support from NEI Grant EY021200,
   NEI Core Grant P30EY013080, and an unrestricted grant from Research to
   Prevent Blindness, Inc. We also thank Dr. Eldon Geisert, Dr. Lu Lu, and
   Mr. Bill Orr for their assistance in generating the BXD microarray
   datasets that were used in these analyses. The XAP-1 monoclonal antibody
   (Clone 3D2 developed by D.S. Sakaguchi and W.A. Harris) was obtained
   from the Developmental Studies Hybridoma Bank, created by the NICHD of
   the NIH and maintained at The University of Iowa, Department of Biology,
   Iowa City, IA 52242.
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NR 48
TC 1
Z9 1
U1 1
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD NOV 10
PY 2016
VL 22
BP 1318
EP 1331
PG 14
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA EK4PF
UT WOS:000393908400001
PM 27881906
DA 2022-11-30
ER

PT J
AU Perepechaeva, ML
   Kolosova, NG
   Stefanova, NA
   Fursova, AZ
   Grishanova, AY
AF Perepechaeva, M. L.
   Kolosova, N. G.
   Stefanova, N. A.
   Fursova, A. Zh.
   Grishanova, A. Y.
TI The influence of changes in expression of redox-sensitive genes on the
   development of retinopathy in rats
SO EXPERIMENTAL AND MOLECULAR PATHOLOGY
LA English
DT Article
DE Retinopathy; Age-related macular degeneration; OXYS rats; OXYSb rats;
   AhR; Nrf2
ID AMD-LIKE RETINOPATHY; POLYUNSATURATED FATTY-ACIDS; RETINAL-PIGMENT
   EPITHELIUM; ARYL-HYDROCARBON RECEPTOR; ACCELERATED OXYS RATS; MACULAR
   DEGENERATION; OXIDATIVE STRESS; HEME OXYGENASE-1; MACROMOLECULAR DAMAGE;
   SIGNALING PATHWAYS
AB Age-related macular degeneration (AMD) is a complex multifactorial disease of the elderly, with unclear pathogenesis; AMD is the leading cause of blindness. One of the destructive processes in AMD is oxidative stress, which leads to an imbalance in the processes responsible for production and detoxification of reactive oxygen species. The aryl hydrocarbon receptor (AhR) signaling pathway can participate in the development of oxidative stress, but the main regulator of antioxidant defense is nuclear factor, erythroid derived 2 (Nrf2). AhR-dependent oxidative stress can be attenuated by activation of Nrf2, and defects in the Nrf2 signaling pathway can increase sensitivity of the cell to oxidative stress. Our aim was to determine the role of the pro-oxidant (AhR-dependent) and antioxidant (Nrf2-dependent) systems in the pathogenesis of AMD using rats of OXYS strain and of OXYSb substrain with signs of AMD-like retinopathy of varying severity. We compared the retinal levels of mRNA expression of Nrf2- and AhR-dependent redox-sensitive systems between 1-, 3-, and 12-month-old senescence accelerated OXYS rats (have been shown to be a valid experimental model of AMD) and the rat substrain OXYSb, which shows low morbidity of AMD. We uncovered interstrain differences in the expression of Nrf2 and Nrf2-dependent genes (glutathione S-reductase [Gsr] and heme oxygenase 1 [Hmox1]), in the expression of AhR-dependent genes (cytochrome P450 1A2 [Cyp1a2] and cytochrome P450 1B1 [Cy1b1]), and in the NADPH-quinone oxidoreductase (Nqol) expression, which is controlled by both AhR and Nrf2. Binding of AhR and Nrf2 proteins to the regulatory regions of AhR and Nrf1 genes, respectively, was detected by chromatin immunoprecipitation in the retina of 1-, 3-, and 12-month-old OXYS, OXYSb, and Wistar (control) rats. We compared the strength of DNA-protein interactions of AhR and Nrf2 with regulatory sequences and found that the level of autoupregulation of the AhR gene was higher in the retina of 1-month-old OXYSb rats in comparison with OXYS rats. An imbalance between pro-oxidant (AhR-dependent) and antioxidant (Nrf2-dependent) systems may play a crucial role in the onset and/or progression of AMD. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Perepechaeva, M. L.; Kolosova, N. G.; Grishanova, A. Y.] Inst Mol Biol & Biophys, Timakova Str 2-12, Novosibirsk 630117, Russia.
   [Kolosova, N. G.; Stefanova, N. A.; Fursova, A. Zh.] Russian Acad Sci, Fed Res Ctr, Siberian Branch, Inst Cytol & Genet, Lavrentiev Ave 10, Novosibirsk 630090, Russia.
   [Kolosova, N. G.] Novosibirsk State Univ, Pirogova Str 2, Novosibirsk 630090, Russia.
C3 Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB
   RAS; Novosibirsk State University
RP Perepechaeva, ML (通讯作者)，Inst Mol Biol & Biophys, Timakova Str 2-12, Novosibirsk 630117, Russia.
EM perepech@niimbb.ru; kolosova@bionet.nsc.ru; stefanovan@bionet.nsc.ru;
   anzhellafursova@yandex.ru; agrish@niimbb.ru
RI Kolosova, Nataliya G/AAR-7409-2020; Grishanova, Alevtina/C-1759-2014;
   Kolosova, Nataliya G/P-3178-2015; Perepechaeva, Maria/AAG-1840-2020;
   fursova, anzhella/AAE-1495-2022; Stefanova, Natalia/V-1530-2018
OI Kolosova, Nataliya G/0000-0003-2398-8544; Grishanova,
   Alevtina/0000-0002-5894-1159; Kolosova, Nataliya G/0000-0003-2398-8544;
   Perepechaeva, Maria/0000-0001-5791-3714; fursova,
   anzhella/0000-0001-6311-5452; Stefanova, natalia/0000-0001-5127-5993
FU Russian Foundation for Basic Research [12-04-01352-a]
FX This work was supported by the Russian Foundation for Basic Research
   (project No. 12-04-01352-a). We thank the "Proteomic analysis" Center of
   the Institute of Molecular Biology and Biophysics (IMBB) for granting
   access to equipment.
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NR 45
TC 4
Z9 4
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4800
EI 1096-0945
J9 EXP MOL PATHOL
JI Exp. Mol. Pathol.
PD AUG
PY 2016
VL 101
IS 1
BP 124
EP 132
DI 10.1016/j.yexmp.2016.07.008
PG 9
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA DU7SX
UT WOS:000382416000017
PM 27466007
DA 2022-11-30
ER

PT J
AU Ho, J
   Adhi, M
   Baumal, C
   Liu, J
   Fujimoto, JG
   Duker, JS
   Waheed, NK
AF Ho, Joseph
   Adhi, Mehreen
   Baumal, Caroline
   Liu, Jonathan
   Fujimoto, James G.
   Duker, Jay S.
   Waheed, Nadia K.
TI AGREEMENT AND REPRODUCIBILITY OF RETINAL PIGMENT EPITHELIAL DETACHMENT
   VOLUMETRIC MEASUREMENTS THROUGH OPTICAL COHERENCE TOMOGRAPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE automated RPED volume; intraclass coefficient
ID MACULAR DEGENERATION; AUTOMATIC SEGMENTATION; DRUSEN
AB Purpose: To assess the agreement and reproducibility of retinal pigment epithelial detachment (RPED) volumetric measurements using a commercially available optical coherence tomography software available for the Zeiss Cirrus HD-OCT.
   Methods: Twelve eyes of 10 patients with a diagnosis of neovascular age-related macular degeneration with RPED, seen at the New England Eye Center between October 2012 and December 2012, were enrolled in the study. Three separate scans per affected eye were obtained using the "Macular Cube 512 x 128" protocol. "Retinal pigment epithelial (RPE) elevation analysis" software was used to measure RPED volumes in the central 3-mm and 5-mm circles by calculating the volume between the "RPE fit" and "true RPE" lines. All 128 raster scans for each eye were exported into the AMIRA software for manual segmentation of RPED volumes in the central 3-mm and 5-mm circles. Interscan reproducibility and manual-to-automated agreement were assessed by intraclass correlation coefficient. Incidence of automated segmentation line error for both RPE fit and true RPE lines in the central 1 mm region was calculated.
   Results: Average RPED volumes through automated segmentation software were 0.14 mm(3) and 0.21 mm(3) in the central 3-mm and 5-mm circles, respectively. Manual segmentation yielded average RPED volumes of 0.50 mm(3) in the 3-mm circles and 0.92 mm(3) in the 5-mm circles. Manual segmentation yielded significantly greater RPED volumes compared with automated measurements (P < 0.05). Intraclass correlation coefficients across the 3 automated measurements were 0.954 and 0.983 for volume in the 3-mm and 5-mm circles, respectively. Intraclass correlation coefficients between the manual and automatic volumes were 0.296 and 0.337 for the 3-mm and 5-mm circles, respectively. In the central 1 mm region, 11 of the 12 scans had breakdown in RPE fit line, whereas 8 of the 12 scans showed true RPE line breakdown.
   Conclusion: Automated "RPED elevation" software demonstrated high interscan reproducibility. However, it showed low agreement with manual measurements from high rates of segmentation line breakdown, especially at the level of the RPE fit line (91.7%). Manual measurements resulted in greater volumes compared with automated measurements.
C1 [Ho, Joseph; Adhi, Mehreen; Baumal, Caroline; Duker, Jay S.; Waheed, Nadia K.] Tufts Med Ctr, Dept Ophthalmol, New England Eye Ctr, Boston, MA USA.
   [Liu, Jonathan; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Cambridge, MA 02139 USA.
C3 Tufts Medical Center; Massachusetts Institute of Technology (MIT)
RP Ho, J (通讯作者)，Tufts Med Ctr, Dept Ophthalmol, 800 Washington St,Box 450, Boston, MA 02111 USA.
EM jho2@tuftsmedicalcenter.org
RI Adhi, Mehreen/AAS-9733-2021
FU Research to Prevent Blindness; NIH [R01-EY11289-24]; Air Force Office of
   Scientific Research [FA9550-07-1-0101, FA9550-07-1-0014]; Carl Zeiss
   Meditec, Inc; Optovue, Inc.; Tufts University School of Medicine;
   NATIONAL EYE INSTITUTE [R01EY011289] Funding Source: NIH RePORTER
FX Supported in part by a Research to Prevent Blindness Challenge grant to
   the New England Eye Center/Department of Ophthalmology, Tufts University
   School of Medicine, NIH contracts R01-EY11289-24, Air Force Office of
   Scientific Research FA9550-07-1-0101 and FA9550-07-1-0014.; J. G.
   Fujimoto receives royalties from intellectual property owned by M.I.T.
   and licensed to Carl Zeiss Meditec, Inc and Optovue, Inc. JG Fujimoto
   has stock options in Optovue, Inc. J. S. Duker receives research support
   from Carl Zeiss Meditec, Inc and Optovue, Inc. The remaining authors
   have no conflicting interests to disclose.
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NR 20
TC 11
Z9 11
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAR
PY 2015
VL 35
IS 3
BP 467
EP 472
DI 10.1097/IAE.0000000000000355
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CC4AO
UT WOS:000350293100025
PM 25545485
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zhang, XZ
   Beckles, GL
   Chou, CF
   Saaddine, JB
   Wilson, MR
   Lee, PP
   Parvathy, N
   Ryskulova, A
   Geiss, LS
AF Zhang, Xinzhi
   Beckles, Gloria L.
   Chou, Chiu-Fang
   Saaddine, Jinan B.
   Wilson, M. Roy
   Lee, Paul P.
   Parvathy, Nair
   Ryskulova, Asel
   Geiss, Linda S.
TI Socioeconomic Disparity in Use of Eye Care Services Among US Adults With
   Age-Related Eye Diseases National Health Interview Survey, 2002 and 2008
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID BLUE MOUNTAINS EYE; VISUAL IMPAIRMENT; UNITED-STATES; OLDER-ADULTS;
   MACULAR DEGENERATION; SOCIAL DETERMINANTS; 2020 VISION; PREVALENCE;
   PEOPLE; RISK
AB IMPORTANCE Individuals with age-related eye disease (ARED) need to use eye care services for detection, assessment, and care at regular intervals.
   OBJECTIVE To explore the association between socioeconomic position (SEP) and use of eye care services among US adults with self-reported ARED during 2002 and 2008.
   DESIGN Data were from the National Health Interview Survey 2002 and 2008. We used multiple logistic regression to estimate predictive margins, controlling for other factors, and we used the slope index of inequality to measure the relationship between SEP and use of eye care services across the entire distributions of poverty-income ratio (PIR) and educational attainment.
   SETTING A cross-sectional, nationally representative sample of adults, with prevalence estimates weighted to represent the civilian, noninstitutionalized US population.
   PARTICIPANTS The sample included US participants in the 2002 (n = 3586) and the 2008 (n = 3104) National Health Interview Survey who were at least 40 years old and reported any ARED (age-related macular degeneration, cataract, diabetic retinopathy, or glaucoma).
   MAIN OUTCOMES AND MEASURES Use of eye care services; SEP was measured by the PIR and educational attainment.
   RESULTS In 2002, persons with ARED and a PIR of less than 1.50 were significantly less likely than those with a PIR of at least 5 to report visiting an eye care provider (62.7% vs 80.1%; P < .001) or undergoing a dilated eye examination in the past 12 months (64.3% vs 80.4%; P < .001), after adjustment for other factors. Similarly, persons with less than a high school education were less likely than those with at least a college education to report a visit to an eye care provider (62.9% vs 80.8%; P < .001) or dilated eye examination (64.8% vs 81.4%; P < .001). In 2002, the slope index of inequality showed statistically significant differences for eye care provider visits across the levels of education (24.4; P = .006), and in 2008, it showed a significant difference for eye care provider visits across the levels of educational attainment (25.2; P = .049) and PIR (21.8; P = .01).
   CONCLUSIONS AND RELEVANCE Significant differences in the use of eye care services by SEP persist among US adults with eye diseases.
C1 [Zhang, Xinzhi; Wilson, M. Roy] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD 20892 USA.
   [Beckles, Gloria L.; Chou, Chiu-Fang; Saaddine, Jinan B.; Parvathy, Nair; Geiss, Linda S.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
   [Lee, Paul P.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
   [Ryskulova, Asel] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute on
   Minority Health & Health Disparities (NIMHD); Centers for Disease
   Control & Prevention - USA; University of Michigan System; University of
   Michigan; Centers for Disease Control & Prevention - USA; CDC National
   Center for Health Statistics (NCHS)
RP Zhang, XZ (通讯作者)，Natl Inst Minor Hlth & Hlth Dispar, Div Data Management & Sci Reporting, NIH, 6707 Democracy Blvd,Ste 800, Bethesda, MD 20892 USA.
EM xinzhi.zhang@nih.gov
FU National Center for Health Statistics, Centers for Disease Control and
   Prevention
FX This study was supported by the National Center for Health Statistics,
   Centers for Disease Control and Prevention.
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NR 52
TC 61
Z9 62
U1 0
U2 11
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD SEP
PY 2013
VL 131
IS 9
BP 1198
EP 1206
DI 10.1001/jamaophthalmol.2013.4694
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 232HC
UT WOS:000325482400012
PM 23868137
OA Bronze
DA 2022-11-30
ER

PT J
AU Seddon, JM
   Reynolds, R
   Yu, Y
   Rosner, B
AF Seddon, Johanna M.
   Reynolds, Robyn
   Yu, Yi
   Rosner, Bernard
TI Validation of a Prediction Algorithm for Progression to Advanced Macular
   Degeneration Subtypes
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; BODY-MASS INDEX; GENOME-WIDE ASSOCIATION;
   AGE-RELATED MACULOPATHY; VARIANT; RISK; GENE; SUSCEPTIBILITY;
   POLYMORPHISM; HTRA1
AB Importance: Risk score models predicting the progression of age-related macular degeneration (AMD) to its advanced forms may be useful for targeting high-risk individuals for lifestyle changes that reduce risk for AMD progression, helping with differential diagnosis of AMD and its subtypes, identifying high-risk subjects for participation in clinical trials, and selecting appropriate therapies.
   Objective: To develop and validate a predictive model for progression to advanced stages of AMD in 2 independent cohorts.
   Design: Participants in a validation cohort and an independent derivation population were classified into 5 stages of AMD based on ocular examination and fundus photographs at baseline. Progression was defined as either eye progressing from stage 1, 2, or 3 to either stage 4 or stage 5 at any follow-up visit to the end of the study. Cox proportional hazards models were used for progression analyses. Covariates included demographic and environmental factors, 6 variants in 5 genes, and baseline AMD grades in both eyes. The algorithm developed with the derivation sample was assessed for calibration and discrimination in the validation data set.
   Setting: Clinic populations and referrals.
   Participants: The derivation population comprised 2914 subjects with 809 progressors. The independent validation cohort comprised 980 individuals with no, early, or intermediate AMD in at least one eye at baseline, of whom 294 progressed to advanced stages of geographic atrophy or neovascular disease.
   Main Outcome Measure: Progression to advanced AMD. Results: For the model with all nongenetic and genetic factors, the respective C statistics for progression to advanced AMD in the derivation and validation samples were 0.858 and 0.750 at 5 years and 0.884 and 0.809 at 10 years, and models also discriminated risk for progression to geographic atrophy and neovascular disease separately. For unilateral or bilateral intermediate AMD, 5-year cumulative incidence rates of progression to advanced AMD were 10% with the low-risk score and 50% with the high-risk score; for unilateral advanced disease, the progression rates were 22% and 80% for the fellow eye.
   Conclusions and Relevance: The risk prediction model was validated in an independent study of progression from no, early, or intermediate stages to advanced subtypes of AMD and will be useful for research, clinical trials, and personalized medicine.
C1 [Seddon, Johanna M.] Tufts Med Ctr, Dept Ophthalmol, Boston, MA 02111 USA.
   [Seddon, Johanna M.; Reynolds, Robyn; Yu, Yi] Tufts Med Ctr, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA.
   [Rosner, Bernard] Tufts Univ, Sch Med, Boston, MA 02111 USA.
   [Rosner, Bernard] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA.
C3 Tufts Medical Center; Tufts Medical Center; Tufts University; Harvard
   University; Harvard Medical School
RP Seddon, JM (通讯作者)，Tufts Med Ctr, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, 800 Washington St,Ste 450, Boston, MA 02111 USA.
EM jseddon@tuftsmedicalcenter.org
FU National Institutes of Health [R01-EY11309]; Massachusetts Lions Eye
   Research Fund Inc; Research to Prevent Blindness Inc; Macula Vision
   Research Foundation; Age-Related Macular Degeneration Research Fund,
   Ophthalmic Epidemiology and Genetics Service, Tufts Medical Center,
   Tufts University School of Medicine, Boston, Massachusetts; NATIONAL EYE
   INSTITUTE [R01EY011309] Funding Source: NIH RePORTER
FX This work was supported by grant R01-EY11309 from the National
   Institutes of Health, the Massachusetts Lions Eye Research Fund Inc,
   unrestricted grants from Research to Prevent Blindness Inc, the Macula
   Vision Research Foundation, and the Age-Related Macular Degeneration
   Research Fund, Ophthalmic Epidemiology and Genetics Service, Tufts
   Medical Center, Tufts University School of Medicine, Boston,
   Massachusetts.
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NR 36
TC 40
Z9 42
U1 0
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD APR
PY 2013
VL 131
IS 4
BP 448
EP 455
DI 10.1001/jamaophthalmol.2013.2578
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 163JH
UT WOS:000320331600004
PM 23411794
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Li, GY
   Fan, B
   Zheng, YC
AF Li, Guang-Yu
   Fan, Bin
   Zheng, Yong-Chen
TI Calcium Overload Is A Critical Step in Programmed Necrosis of ARPE-19
   Cells Induced by High-Concentration H2O2
SO BIOMEDICAL AND ENVIRONMENTAL SCIENCES
LA English
DT Article
DE Apoptosis; ARPE-19 cell; Necrosis; Oxidative-stressed injury; Hydrogen
   peroxide
ID RETINAL-PIGMENT EPITHELIUM; OXIDATIVE TISSUE-INJURIES; HEME OXYGENASE-1;
   APOPTOSIS; DEATH; STRESS; MITOCHONDRIA; ACTIVATION; CHANNELS; DAMAGE
AB Objective Oxidative stress plays an important role in retinal pigmental epithelium (RPE) death during aging and the development of age-related macular degeneration. Although early reports indicate that reactive oxygen species (ROS) including H2O2 can trigger apoptosis at lower concentrations and necrosis at higher concentrations, the exact molecular mechanism of RPE death is still unclear. The purpose of this study was to investigate the molecular pathways involved in RPE death induced by exogenous ROS, especially at higher concentrations. Methods Cultured ARPE-19 cells were treated with H2O2 at different concentrations and cell viability was measured with the MTT assay. Cell death was morphologically studied by microscopy using APOPercentage assay and PI staining. Furthermore, the impact of oxidative stress on ARPE-19 cells was assessed by HO-1 and PARP-1 Western blotting and by the protection of antioxidant EGCG. Calcium influx was determined using the fura-2 calcium indicator and the role of intracellular calcium overload in ARPE-19 cell death was evaluated following cobalt treatment to block calcium effects. Results H2O2 reduced the viability of ARPE-19 cells in a concentration-dependent manner, which was presented as a typical s-shaped curve. Cell death caused by high concentrations of H2O2 was confirmed to be programmed necrosis. Morphologically, dying ARPE-19 cells were extremely swollen and lost the integrity of their plasma membrane, positively detected with APOPercentage assay and PI staining. 24-hour treatment with 500 mu mol/L H2O2 induced remarkable up-regulation of HO-1 and PARP-1 in ARPE-19 cells. Moreover, antioxidant treatment using EGCG effectively protected cells from H2O2-induced injury, increasing cell viability from 14.17%+/- 2.31% to 85.77%+/- 4.58%. After H2O2 treatment, intracellular calcium levels were highly elevated with a maximum concentration of 1200nM. Significantly, the calcium channel inhibitor cobalt was able to blunt this calcium influx and blocked the necrotic pathway, rescuing the ARPE-19 cell from H2O2-induced death. Conclusions At high concentrations, H2O2 induces ARPE-19 cell death through a regulated necrotic pathway with calcium overload as a critical step in the cell death program.
C1 [Li, Guang-Yu; Fan, Bin; Zheng, Yong-Chen] Jilin Univ, Hosp 2, Dept Ophthalmol, Changchun 130041, Jilin, Peoples R China.
C3 Jilin University
RP Li, GY (通讯作者)，Jilin Univ, Hosp 2, Dept Ophthalmol, Changchun 130041, Jilin, Peoples R China.
EM liguangyu_box@yahoo.com.cn
FU Natural Science Foundation of China [30801271]; Changchun Science and
   Technology Development Fund [08SF39]; Science and Technology Bureau of
   Jilin Province [20090746]
FX This work was supported by grants from the Natural Science Foundation of
   China (30801271), the Changchun Science and Technology Development Fund
   (08SF39) and the International Joint Project from Science and Technology
   Bureau of Jilin Province (20090746).
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NR 41
TC 43
Z9 45
U1 1
U2 15
PU CHINESE CENTER DISEASE CONTROL & PREVENTION
PI BEIJING
PA 155 CHANGBAI RD, CHANGPING DISTRICT, BEIJING, 102206, PEOPLES R CHINA
SN 0895-3988
J9 BIOMED ENVIRON SCI
JI Biomed. Environ. Sci.
PD OCT
PY 2010
VL 23
IS 5
BP 371
EP 377
DI 10.1016/S0895-3988(10)60078-5
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health
GA 682IB
UT WOS:000284393500006
PM 21112485
DA 2022-11-30
ER

PT J
AU Konstantinidis, L
   Mameletzi, E
   Mantel, I
   Pournaras, JA
   Zografos, L
   Ambresin, A
AF Konstantinidis, Lazaros
   Mameletzi, Evangelia
   Mantel, Irmela
   Pournaras, Jean-Antoine
   Zografos, Leonidas
   Ambresin, Aude
TI Intravitreal ranibizumab (LucentisA (R)) in the treatment of retinal
   angiomatous proliferation (RAP)
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Retinal angiomatous proliferation;
   Ranibizumab
ID BEVACIZUMAB AVASTIN TREATMENT; PHOTODYNAMIC THERAPY; TRIAMCINOLONE
   ACETONIDE; SURGICAL ABLATION; MACULAR DEGENERATION; LASER
   PHOTOCOAGULATION; GROWTH-FACTOR; NEOVASCULARIZATION; FAMILY
AB Retinal angiomatous proliferation (RAP) is a distinct variant of neovascular age-related macular degeneration (AMD). The aim of this study is to evaluate the functional and anatomic outcome after intravitreal ranibizumab (Lucentis) treatment in patients with RAP.
   Prospective study of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein and indocyanine green angiography were performed at baseline and repeated at least every 3 months.
   Thirty-one eyes of 31 patients were treated with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean age of the patients was 82.6 years (SD:4.9). The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR BCVA was improved significantly (P < 0.0001) at the last follow-up to 0.45, SD: 0.3 (decimal equivalent 0.35). The visual acuity (VA) improved by a mean of 2.7 lines (SD 2.5). Mean baseline central macular thickness (CMT) was 376 mu m, and decreased significantly to a mean of 224 mu m (P < 0.001) at the last follow-up. Mean reduction of CMT was 152 mu m (SD: 58). An average of 81.5% of the total visual improvement and 85% of the total CMT reduction occurred during the first post-operative month after one intravitreal injection of ranibizumab. During follow-up, an RPE tear occurred in one eye (3.2%) of the study group. No injection complications or systemic drug-related side-effects were noted during the follow-up period.
   Intravitreal ranibizumab injections appeared to be an effective and safe treatment for RAP, resulting in visual gain and reduction in macular thickness. Further long-term studies to evaluate the efficacy of intravitreal ranibizumab in RAP are warranted.
C1 [Konstantinidis, Lazaros; Mameletzi, Evangelia; Mantel, Irmela; Pournaras, Jean-Antoine; Zografos, Leonidas; Ambresin, Aude] Univ Lausanne, Hop Ophtalm Jules Gonin, CH-1004 Lausanne, Switzerland.
C3 University of Lausanne
RP Ambresin, A (通讯作者)，Univ Lausanne, Hop Ophtalm Jules Gonin, 15 Av France, CH-1004 Lausanne, Switzerland.
EM aude.ambresin@fa2.ch
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NR 37
TC 41
Z9 43
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD SEP
PY 2009
VL 247
IS 9
BP 1165
EP 1171
DI 10.1007/s00417-009-1089-3
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 483PH
UT WOS:000268979200002
PM 19404661
OA Green Published
DA 2022-11-30
ER

PT J
AU Leat, SJ
   Mei, M
AF Leat, Susan J.
   Mei, Ming
TI Custom-devised and generic digital enhancement of images for people with
   maculopathy
SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS
LA English
DT Article
DE age-related maculopathy; contrast sensitivity; digital image processing;
   image enhancement; low vision; macular degeneration; supra-threshold
   contrast matching
ID MACULAR DEGENERATION; CONTRAST CONSTANCY; READING PERFORMANCE; NATURAL
   IMAGES; HUMAN-VISION; AGE; SENSITIVITY; RECOGNITION; TELEVISION;
   PERCEPTION
AB The purpose of this study was to compare the effectivity, in terms of the potential usefulness, of digital filters based on either contrast sensitivity (CS) or supra-threshold contrast matching (CM) in enhancing pictures images for people with maculopathy and to investigate whether generic filters (not based on an individual's vision loss) are equally as effective. Effectivity is measured by changes in perceived visibility.
   Thirty-five subjects with maculopathy, aged 20-92 years, took part [13 atrophic age-related macular degeneration (ARMD), 14 exudative ARMD, and 8 juvenile macular dystrophy (JMD)]. CS and supra-threshold CM were measured. A range of CS filters (1 or 2-octave wide band-pass filter using a Gabor or polynomial envelope) with different strengths were developed based on the ratio of the individual's contrast threshold and that of a normal age-related group. Similarly filters were developed based on CM at 3.6% and 27.9% contrast. The following generic filters were also applied with different 'strengths': edge enhancement; sharpening; contrast enhancement; Peli's adaptive enhancement; difference of Gaussian; and an equi-emphasis band-pass filter. The filters were applied to images of faces and general scenes. Subjects were asked to rank the perceived visibility of images (to obtain the best version of each filter) and then to rate the perceived visibility of each image filtered with a particular filter.
   In general, subjects with atrophic ARMD and JMD preferred the weaker versions of most of the filters, while those with exudative ARMD did not show such a clear preference. Generally, images of faces were preferred with less enhancement than scenes. The filters based on CM were rated as giving significant improvement, while those based on CS and peak emphasis were not preferred. Of the generic filters, the Peli adaptive enhancement filter was most frequently rated as giving a significant improvement (p < 0.05) followed by the contrast enhancement filter. They gave the same perceived enhancement as the custom-devised filters.
   Generic filters, which are easier to apply than the custom-devised filters, are appropriate for rehabilitation purposes.
C1 [Leat, Susan J.] Univ Waterloo, Sch Optometry, Waterloo, ON N2L 3G1, Canada.
   [Mei, Ming] York Univ, Ctr Vis Res, Toronto, ON M3J 2R7, Canada.
C3 University of Waterloo; York University - Canada
RP Leat, SJ (通讯作者)，Univ Waterloo, Sch Optometry, Waterloo, ON N2L 3G1, Canada.
EM leat@uwaterloo.ca
OI Leat, Susan/0000-0002-7082-035X
FU Macular Disease Society, UK
FX We would like to thank Ed Jernigan for comments on the text and for
   advice regarding filters, Gordon Deng and Fu Jin for software
   development and development of filters and Wen Zhang for work with the
   DoG filters. Also, thanks is given to Jeff Hovis who provided help with
   image classification and Trefford Simpson who helped with the
   experimental set-up for the contrast matching data. This study was
   supported by the Macular Disease Society, UK.
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NR 38
TC 5
Z9 5
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-5408
EI 1475-1313
J9 OPHTHAL PHYSL OPT
JI Ophthalmic Physiol. Opt.
PD JUL
PY 2009
VL 29
IS 4
BP 397
EP 415
DI 10.1111/j.1475-1313.2008.00633.x
PG 19
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 453KV
UT WOS:000266610200002
PM 19292829
DA 2022-11-30
ER

PT J
AU Kalathur, RKR
   Gagniere, N
   Berthommier, G
   Poidevin, L
   Raffelsberger, W
   Ripp, R
   Leveillard, T
   Poch, O
AF Kalathur, Ravi Kiran Reddy
   Gagniere, Nicolas
   Berthommier, Guillaume
   Poidevin, Laetitia
   Raffelsberger, Wolfgang
   Ripp, Raymond
   Leveillard, Thierry
   Poch, Olivier
TI RETINOBASE: a web database, data mining and analysis platform for gene
   expression data on retina
SO BMC GENOMICS
LA English
DT Article
ID NUCLEAR RECEPTOR NR2E3; CONGENITAL AMAUROSIS; MOUSE MODEL;
   IDENTIFICATION; TRANSCRIPTION; BIOCONDUCTOR; PROFILES; DENSITY; EYE
AB Background: The retina is a multi-layered sensory tissue that lines the back of the eye and acts at the interface of input light and visual perception. Its main function is to capture photons and convert them into electrical impulses that travel along the optic nerve to the brain where they are turned into images. It consists of neurons, nourishing blood vessels and different cell types, of which neural cells predominate. Defects in any of these cells can lead to a variety of retinal diseases, including age-related macular degeneration, retinitis pigmentosa, Leber congenital amaurosis and glaucoma. Recent progress in genomics and microarray technology provides extensive opportunities to examine alterations in retinal gene expression profiles during development and diseases. However, there is no specific database that deals with retinal gene expression profiling. In this context we have built RETINOBASE, a dedicated microarray database for retina.
   Description: RETINOBASE is a microarray relational database, analysis and visualization system that allows simple yet powerful queries to retrieve information about gene expression in retina. It provides access to gene expression metadata and offers significant insights into gene networks in retina, resulting in better hypothesis framing for biological problems that can subsequently be tested in the laboratory. Public and proprietary data are automatically analyzed with 3 distinct methods, RMA, dChip and MAS5, then clustered using 2 different K-means and 1 mixture models method. Thus, RETINOBASE provides a framework to compare these methods and to optimize the retinal data analysis. RETINOBASE has three different modules, "Gene Information", "Raw Data System Analysis" and "Fold change system Analysis" that are interconnected in a relational schema, allowing efficient retrieval and cross comparison of data. Currently, RETINOBASE contains datasets from 28 different microarray experiments performed in 5 different model systems: drosophila, zebrafish, rat, mouse and human. The database is supported by a platform that is designed to easily integrate new functionalities and is also frequently updated.
   Conclusion: The results obtained from various biological scenarios can be visualized, compared and downloaded. The results of a case study are presented that highlight the utility of RETINOBASE. Overall, RETINOBASE provides efficient access to the global expression profiling of retinal genes from different organisms under various conditions.
C1 [Kalathur, Ravi Kiran Reddy; Gagniere, Nicolas; Berthommier, Guillaume; Poidevin, Laetitia; Raffelsberger, Wolfgang; Ripp, Raymond; Poch, Olivier] Inst Genet & Biol Mol & Cellulaire, Lab Bioiformat & Genom Integrat, CNRS, INSERM,ULP, F-67404 Illkirch Graffenstaden, France.
   [Leveillard, Thierry] Univ Paris 06, INSERM, Lab Physiopathol Cellulaire & Mol Retine, Hop St Antoine,U592, Paris, France.
C3 Centre National de la Recherche Scientifique (CNRS); Institut National
   de la Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Universites de Strasbourg Etablissements Associes;
   Universite de Strasbourg; Assistance Publique Hopitaux Paris (APHP);
   Hopital Universitaire Saint-Antoine - APHP; Institut National de la
   Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite
RP Poch, O (通讯作者)，Inst Genet & Biol Mol & Cellulaire, Lab Bioiformat & Genom Integrat, CNRS, INSERM,ULP, BP 163, F-67404 Illkirch Graffenstaden, France.
EM ravi@igbmc.u-strasbg.fr; gagniere@igbmc.u-strasbg.fr;
   berthomg@igbmc.u-strasbg.fr; Laetitia.Poidevin@igbmc.u-strasbg.fr;
   wraff@igbmc.u-strasbg.fr; ripp@igbmc.u-strasbg.fr;
   Thierry.Leveillard@st-antoine.inserm.fr; poch@titus.u-strasbg.fr
RI Léveillard, Thierry/AAR-1804-2020
OI Léveillard, Thierry/0000-0001-5692-8770; Kalathur, Ravi Kiran
   Reddy/0000-0003-2894-3345
CR Abou-Sleymane G, 2006, HUM MOL GENET, V15, P691, DOI 10.1093/hmg/ddi483
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NR 49
TC 11
Z9 12
U1 0
U2 5
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD MAY 5
PY 2008
VL 9
AR 208
DI 10.1186/1471-2164-9-208
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 308OG
UT WOS:000256399300002
PM 18457592
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Nirmalan, PK
   Katz, J
   Tielsch, JM
   Robin, AL
   Thulasiraj, RD
   Krishnadas, R
   Ramakrishnan, R
AF Nirmalan, PK
   Katz, J
   Tielsch, JM
   Robin, AL
   Thulasiraj, RD
   Krishnadas, R
   Ramakrishnan, R
TI Ocular trauma in a rural south Indian population - The aravind
   comprehensive eye survey
SO OPHTHALMOLOGY
LA English
DT Article
ID URBAN-POPULATION; ANDHRA-PRADESH; BLINDNESS; EPIDEMIOLOGY; IMPAIRMENT;
   PATTERNS; DISEASE; BURDEN; NEPAL
AB Purpose: To determine the rate of ocular trauma in a rural population of southern India and its impact on vision impairment and blindness.
   Methods: A population-based cross-sectional study of 5150 persons 40 years or older in a randomly chosen rural population of 3 districts of southern India. Prospective information on trauma, type and agent of injury, setting of injury, and details of treatment sought for the last episode was recorded with questionnaires after face-to-face interviews. All interviewed subjects underwent a comprehensive ocular examination, including vision estimations, slit-lamp biomicroscopy examinations, and dilated posterior segment examinations.
   Results: We elicited a history of ocular trauma in either eye from 229 (4.5%) persons, including 21 (0.4%) persons with bilateral ocular trauma. Blunt injuries (n = 124; 54.9%) were the major cause for trauma reported in this population. The most common setting where the ocular trauma occurred was during agricultural labor (n - 107; 46.9%). Nearly three quarters (n = 170; 74.2%) of those reporting ocular trauma sought treatment from an eye specialist (n = 104; 57.8%) and one fifth (n = 37; 20.6%) from a traditional healer. The age-adjusted (adjusted to the population estimates for India for the year 2000) prevalence for blindness in any eye caused by trauma was 0.8% (95% confidence interval [CI], 0.4-1.1). The odds ratios (OR) for trauma were higher for males (OR, 2.2; 95% CI, 1.6-3.0) and laborers (OR, 1.7; 95% CI, 1.2-2.4) and lower for literates (OR, 0.7; 95% CI, 0.50.9). Seeking treatment from a traditional eye healer for trauma was not associated with vision impairment (OR, 1.0; 95% CI, 0.3-3.2) or with blindness (OR, 3.4; 95% CI, 0.2-56.5).
   Conclusions: Eye care programs may need to consider ocular trauma as a priority in this population, because the lifetime prevalence of ocular trauma is higher than that reported for glaucoma, age-related macular degeneration, or diabetic retinopathy from this population. Simple measures such as education regarding the use of protective eyewear could possibly significantly decrease this preventable cause of visual disability. (C) 2004 by the American Academy of Ophthalmology.
C1 Aravind Eye Care Syst, Aravind Med Res Fdn, Madurai, Tamil Nadu, India.
   Aravind Eye Care Syst, Lions Aravind Inst Community Ophthalmol, Madurai, Tamil Nadu, India.
   Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
   Johns Hopkins Univ, Sch Med, Dana Ctr Prevent Ophthalmol, Baltimore, MD USA.
   Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD USA.
C3 Johns Hopkins University; Johns Hopkins Bloomberg School of Public
   Health; Johns Hopkins University; Johns Hopkins University
RP Robin, AL (通讯作者)，Lake Falls Profess Bldg,6115 Falls Rd,Suite 333, Baltimore, MD USA.
EM glaucomaexpert@cs.com
OI Katz, Joanne/0000-0002-5997-7823; Tielsch, James/0000-0002-1151-060X;
   Robin, Alan/0000-0003-1959-8770; Nirmalan, Praveen/0000-0003-0655-8104
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NR 20
TC 65
Z9 66
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD SEP
PY 2004
VL 111
IS 9
BP 1778
EP 1781
DI 10.1016/j.ophtha.2004.02.012
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 850JD
UT WOS:000223606300025
PM 15350336
DA 2022-11-30
ER

PT J
AU Gunasekeran, DV
   Zheng, FH
   Lim, GYS
   Chong, CCY
   Zhang, SH
   Ng, WY
   Keel, S
   Xiang, YF
   Park, KH
   Park, SJ
   Chandra, A
   Wu, L
   Campbel, JP
   Lee, AY
   Keane, PA
   Denniston, A
   Lam, DSC
   Fung, AT
   Chan, PRV
   Sadda, SR
   Loewenstein, A
   Grzybowski, A
   Fong, KCS
   Wu, WC
   Bachmann, LM
   Zhang, XL
   Yam, JC
   Cheung, CY
   Pongsachareonnont, P
   Ruamviboonsuk, P
   Raman, R
   Sakamoto, T
   Habash, R
   Girard, M
   Milea, D
   Ang, M
   Tan, GSW
   Schmetterer, L
   Cheng, CY
   Lamoureux, E
   Lin, HT
   van Wijngaarden, P
   Wong, TY
   Ting, DSW
AF Gunasekeran, Dinesh V. V.
   Zheng, Feihui
   Lim, Gilbert Y. S.
   Chong, Crystal C. Y.
   Zhang, Shihao
   Ng, Wei Yan
   Keel, Stuart
   Xiang, Yifan
   Park, Ki Ho
   Park, Sang Jun
   Chandra, Aman
   Wu, Lihteh
   Campbel, J. Peter
   Lee, Aaron Y. Y.
   Keane, Pearse A. A.
   Denniston, Alastair
   Lam, Dennis S. C.
   Fung, Adrian T. T.
   Chan, Paul R. V.
   Sadda, SriniVas R.
   Loewenstein, Anat
   Grzybowski, Andrzej
   Fong, Kenneth C. S.
   Wu, Wei-chi
   Bachmann, Lucas M.
   Zhang, Xiulan
   Yam, Jason C.
   Cheung, Carol Y. Y.
   Pongsachareonnont, Pear
   Ruamviboonsuk, Paisan
   Raman, Rajiv
   Sakamoto, Taiji
   Habash, Ranya
   Girard, Michael
   Milea, Dan
   Ang, Marcus
   Tan, Gavin S. W.
   Schmetterer, Leopold
   Cheng, Ching-Yu
   Lamoureux, Ecosse
   Lin, Haotian
   van Wijngaarden, Peter
   Wong, Tien Y. Y.
   Ting, Daniel S. W.
TI Acceptance and Perception of Artificial Intelligence Usability in Eye
   Care (APPRAISE) for Ophthalmologists: A Multinational Perspective
SO FRONTIERS IN MEDICINE
LA English
DT Article
DE ophthalmology; artificial intelligence (AI); regulation; implementation;
   translation
ID TECHNOLOGY; PREDICTION; BLINDNESS; HEALTH
AB BackgroundMany artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract. MethodsThis was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning. ResultsOne thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10-12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63-0.83. ConclusionOphthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology.
C1 [Gunasekeran, Dinesh V. V.; Zheng, Feihui; Lim, Gilbert Y. S.; Chong, Crystal C. Y.; Zhang, Shihao; Ng, Wei Yan; Girard, Michael; Milea, Dan; Ang, Marcus; Tan, Gavin S. W.; Schmetterer, Leopold; Cheng, Ching-Yu; Lamoureux, Ecosse; Wong, Tien Y. Y.; Ting, Daniel S. W.] Singapore Natl Eye Ctr SNEC, Singapore Eye Res Inst SERI, Singapore, Singapore.
   [Gunasekeran, Dinesh V. V.; Ang, Marcus; Tan, Gavin S. W.; Schmetterer, Leopold; Cheng, Ching-Yu; Lamoureux, Ecosse; Wong, Tien Y. Y.; Ting, Daniel S. W.] Natl Univ Singapore NUS, Sch Med, Singapore, Singapore.
   [Gunasekeran, Dinesh V. V.; Lim, Gilbert Y. S.; Girard, Michael; Ang, Marcus; Tan, Gavin S. W.; Schmetterer, Leopold; Cheng, Ching-Yu; Lamoureux, Ecosse; Wong, Tien Y. Y.; Ting, Daniel S. W.] Duke NUS Med Sch, Singapore, Singapore.
   [Keel, Stuart; van Wijngaarden, Peter] Univ Melbourne, Dept Ophthalmol, Melbourne, Vic, Australia.
   [Xiang, Yifan; Zhang, Xiulan; Lin, Haotian] Sun Yat sen Univ, Zhongshan Ophthalm Ctr ZOC, State Key Lab Ophthalmol, Guangzhou, Peoples R China.
   [Park, Ki Ho; Park, Sang Jun] Seoul Natl Univ, Dept Ophthalmol, Coll Med, Seoul, South Korea.
   [Park, Sang Jun] Seoul Natl Univ, Dept Ophthalmol, Bundang Hosp, Seongnam, South Korea.
   [Chandra, Aman] Southend Univ Hosp, Dept Ophthalmol, Southend on Sea, England.
   [Wu, Lihteh] Asociados Macula Vitreo & Retina Costa Rica, San Jose, Costa Rica.
   [Campbel, J. Peter] Casey Eye Inst Oregon Hlth & Sci, Portland, OR USA.
   [Lee, Aaron Y. Y.] Univ Washington, Dept Ophthalmol, Seattle, WA USA.
   [Keane, Pearse A. A.] Moorfields Eye Hosp, London, England.
   [Denniston, Alastair] Univ Hosp Birmingham NHS Fdn Trust, Dept Ophthalmol, Birmingham, Warwickshire, England.
   [Denniston, Alastair] Univ Coll London UCL, Inst Ophthalmol, London, England.
   [Lam, Dennis S. C.] Chinese Univ Hong Kong Shenzhen, Int Eye Res Inst, Shenzhen, Peoples R China.
   [Lam, Dennis S. C.] Chinese Univ Hong Kong Shenzhen, C MER Int Eye Res Ctr, Shenzhen, Peoples R China.
   [Fung, Adrian T. T.] Univ Sydney, Fac Med & Hlth, Westmead Clin Sch, Specialty Clin Ophthalmol & Eye Hlth, Sydney, NSW, Australia.
   [Fung, Adrian T. T.] Macquarie Univ Hosp, Fac Med Hlth & Human Sci, Dept Ophthalmol, Sydney, NSW, Australia.
   [Chan, Paul R. V.] Univ Illinois, Dept Ophthalmol, Coll Med, Chicago, IL USA.
   [Sadda, SriniVas R.] Doheny Eye Inst, Dept Ophthalmol, Los Angeles, CA USA.
   [Loewenstein, Anat] Tel Aviv Med Ctr & Sch Med, Dept Ophthalmol, Tel Aviv, Israel.
   [Grzybowski, Andrzej] Univ Warm & Mazury, Dept Ophthalmol, Olsztyn, Poland.
   [Grzybowski, Andrzej] Inst Res Ophthalmol, Ponzan, Poland.
   [Fong, Kenneth C. S.] OasisEye Specialists, Kuala Lumpur, Malaysia.
   [Wu, Wei-chi] Chang Gung Mem Hosp, Dept Ophthalmol, Taoyuan, Taiwan.
   [Bachmann, Lucas M.] Oculocare Med AG, Zurich, Switzerland.
   [Yam, Jason C.; Cheung, Carol Y. Y.] Chinese Univ Hong Kong CUHK, Dept Ophthalmol & Visual Sci, Hong Kong, Peoples R China.
   [Pongsachareonnont, Pear] Chulalongkorn Univ, King Chulalongkorn Mem Hosp, Dept Ophthalmol, Vitreoretinal Res Unit, Bangkok, Thailand.
   [Ruamviboonsuk, Paisan] Rangsit Univ, Rajavithi Hosp, Coll Med, Dept Ophthalmol, Bangkok, Thailand.
   [Raman, Rajiv] Vitreo Retinal Dept, Sankara Nethralaya, Chennai, India.
   [Sakamoto, Taiji] Kagoshima Univ, Dept Ophthalmol, Kagoshima, Japan.
   [Habash, Ranya] Bascom Palmar Eye Inst, Miami, FL USA.
   [Milea, Dan] Copenhagen Univ Hosp, Copenhagen, Denmark.
   [Wong, Tien Y. Y.] Tsinghua Univ, Tsinghua Med, Beijing, Peoples R China.
C3 National University of Singapore; University of Melbourne; Sun Yat Sen
   University; Seoul National University (SNU); Seoul National University
   (SNU); University of Washington; University of Washington Seattle;
   University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of Birmingham; University of London;
   University College London; Chinese University of Hong Kong, Shenzhen;
   Chinese University of Hong Kong, Shenzhen; University of Sydney;
   Macquarie University; University of Illinois System; University of
   Illinois Chicago; University of Illinois Chicago Hospital; Doheny Eye
   Institute; Tel Aviv University; Sackler Faculty of Medicine; Chang Gung
   Memorial Hospital; Chulalongkorn University; Rajavithi Hospital; Rangsit
   University; Kagoshima University; University of Copenhagen; Tsinghua
   University
RP Ting, DSW (通讯作者)，Singapore Natl Eye Ctr SNEC, Singapore Eye Res Inst SERI, Singapore, Singapore.; Ting, DSW (通讯作者)，Natl Univ Singapore NUS, Sch Med, Singapore, Singapore.; Ting, DSW (通讯作者)，Duke NUS Med Sch, Singapore, Singapore.
EM daniel.ting.s.w@singhealth.com.sg
RI CHENG, FREYA/GOH-0443-2022; Cheng, Ching-Yu/Y-2229-2019
OI CHENG, FREYA/0000-0001-9179-3461; Cheng, Ching-Yu/0000-0003-0655-885X;
   Keane, Pearse/0000-0002-9239-745X
FU Santen; Genentech; US FDA; Johnson and Johnson; CarlZeiss Meditec;
   Topcon; Gyroscope; Regeneron; Heidelberg Engineering; Allergan; Bayer;
   Alcon; Novartis; Roche; Syneos Health; Singapore National Medical
   Research Council; Duke-NUS Medical School, Singapore
   [NMRC-CIRG18Nov-0013]; National Medical Research Council, Singapore [ACP
   05/FY2019/P2/06-A60, NHIC-COV19-2005017, SHF/HSR113/2017]; National
   Health Innovation Center, Singapore [Duke-NUS/RSF/2021/0018,
   05/FY2020/EX/15-A58]; SingHealth Fund Limited Foundation
   [NMRC/HSRG/0087/2018]; Agency for Science, Technology and Research
   (ASTAR), Singapore [MOH-000655-00];  [A20H4g2141]
FX DG reports appointment as Physician Leader (Telemedicine)for Raffles
   Medical Group (SGX:$BSL.SI) and investments in digital healthstart-ups
   AskDr, Doctorbell (acquired by MaNaDr), Shyfts, and VISRE. JC
   reportsappointment as a consultant to Boston AI labs. AYL reports grants
   from Santen,personal fees from Genentech, US FDA, Johnson and Johnson,
   grants from CarlZeiss Meditec, personal fees from Topcon, Gyroscope,
   non-financial support from Microsoft, grants from Regeneron, outside the
   submitted work; This article doesnot reflect the views of the US FDA. PK
   reports having acted as a consultantfor DeepMind, Roche, Novartis,
   Apellis, and BitFount and is an equity owner inBig Picture Medical. He
   has received speaker fees from Heidelberg Engineering,Topcon, Allergan,
   and Bayer. AF reports honoraria, advisory board and grantfunding from
   Alcon, Bayer, Novartis, Allergan, Roche, and Syneos Health. ALreports
   grants from Roche and Novartis, and appointment as a
   consultanttoNotalVision, Allergan, Bayer, WebMD, and Beyeonics. AG
   reports appointmentto provide lectures for Pfizer, Thea, and Polpharma.
   TS reports appointmentas a consultant & advisory board for Bayer
   Yakuhin, Boehringer-Ingelheim,Novartis, Chugai, Senju, and Santen. DM
   reports funding support fromthe Singapore National Medical Research
   Council (NMRC-CIRG18Nov-0013), andthe Duke-NUS Medical School, Singapore
   (ACP 05/FY2019/P2/06-A60). DM also reports appointment as consultant and
   Advisory Board Member of Optomed, Finland. TW reports appointment as the
   deputy group chief executive officer(research and education) of
   Singapore Health Services, a consultant & advisory board for Allergan,
   Bayer, Boehringer-Ingelheim, Genentech, Merck, Novartis, Oxurion
   (formerly ThromboGenics), Roche, and co-founder of Plano. DT reports
   funding from the following grants for research about AI in healthcare:
   National Medical Research Council, Singapore (NMRC/HSRG/0087/2018;
   MOH-000655-00), National Health Innovation Center, Singapore
   (NHIC-COV19-2005017),SingHealth Fund Limited Foundation
   (SHF/HSR113/2017), Duke-NUS Medical School, Singapore
   (Duke-NUS/RSF/2021/0018; 05/FY2020/EX/15-A58), and Agency for Science,
   Technology and Research (ASTAR), Singapore (A20H4g2141 and A20H4g2141).
   DT, GL, and TW also report being the co-inventorsof a deeplearning
   system for retinal diseases and co-founders of related start-up
   Eyris;potential conflicts of interests are managed according to
   institutional policies of the Singapore Health System (SingHealth) and
   the National University of Singapore (NUS).
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NR 53
TC 0
Z9 0
U1 1
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 2296-858X
J9 FRONT MED-LAUSANNE
JI Front. Med.
PD OCT 13
PY 2022
VL 9
AR 875242
DI 10.3389/fmed.2022.875242
PG 19
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 5U2LN
UT WOS:000876385000001
PM 36314006
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Nanji, K
   Sarohia, GS
   Kennedy, K
   Ceyhan, T
   McKechnie, T
   Phillips, M
   Devji, T
   Thabane, L
   Kaiser, P
   Sarraf, D
   Garg, SJ
   Sivaprasad, S
   Wykoff, CC
   Bakri, SJ
   Sheidow, T
   Bhandari, M
   Chaudhary, V
AF Nanji, Keean
   Sarohia, Gurkaran S.
   Kennedy, Kevin
   Ceyhan, Tiandra
   McKechnie, Tyler
   Phillips, Mark
   Devji, Tahira
   Thabane, Lehana
   Kaiser, Peter
   Sarraf, David
   Garg, Sunir J.
   Sivaprasad, Sobha
   Wykoff, Charles C.
   Bakri, Sophie J.
   Sheidow, Tom
   Bhandari, Mohit
   Chaudhary, Varun
TI The 12-and 24-Month Effects of Intravitreal Ranibizumab, Aflibercept,
   and Bevacizumab on Intraocular Pressure A Network Meta-Analysis
SO OPHTHALMOLOGY
LA English
DT Article
DE Anti-VEGF therapy; Diabetic macular edema; Neovascular age-related;
   macular degeneration; Ocular hypertension; Retinal vein occlusion
ID ANTERIOR-CHAMBER PARACENTESIS; GROWTH-FACTOR AGENTS; MACULAR
   DEGENERATION; SUSTAINED ELEVATION; INJECTION; LASER; METAANALYSIS;
   MONOTHERAPY; TRIAL; RISK
AB Topic: To investigate the effect of anti-vascular endothelial growth factor (VEGF) therapy on intraocular pressure (IOP) 12 and 24 months after initiation.
   Clinical Relevance: It is unclear whether serial anti-VEGF injections result in sustained IOP increases.
   Methods: Randomized controlled trials (RCTs) comparing anti-VEGF agents with each other or with controls for the treatment of neovascular age-related macular degeneration, retinal vein occlusions, or diabetic macular edema were included. Pairwise meta-analysis and Bayesian network meta-analysis examined the proportion of patients whose IOP (1) increased 5 mmHg or more from baseline on consecutive visits, (2) increased 10 mmHg or more from baseline at any visit, (3) was 21 mmHg or more on consecutive visits, (4) was 25 mmHg or more at any visit, (5) was 30 mmHg or more at any visit, (6) prompted initiation of IOP-lowering medications, or (7) increased as per the clinicians' discretion. Grading of Recommendations Assessments, Development, and Evaluations methodology informed the certainty of evidence.
   Results: Twenty-six RCTs of 12 522 eyes were included. Aflibercept, bevacizumab, ranibizumab (0.3 mg and 0.5 mg), and noninjection controls were analyzed. Eighty-three of 84 network estimates for comparisons between anti-VEGF agents demonstrated no statistically significant difference (low to moderate certainty of evidence). Ranibizumab 0.5 mg showed higher rates than bevacizumab of IOP measurements of 30 mmHg or more at 12 months (low certainty of evidence). Fifty-three of 56 network estimates for comparisons between anti-VEGF agents and controls demonstrated no statistically significant difference (low to moderate certainty of evidence). Ranibizumab 0.5 mg showed higher rates of consecutive IOP increases of 5 mmHg or more at 24 months (low certainty of evidence) and higher rates of IOP increases as per the clinicians' discretion at 12 and 24 months (low and very low certainty of evidence, respectively). The 95% credible intervals in comparisons without statistically significant effects did not rule out important clinical effects. The certainty of evidence in these comparisons is limited by imprecision.
   Conclusion: This network meta-analysis does not show any clear difference in !OP increases 12 and 24 months after treatment initiation between anti-VEGF agents and controls. Imprecision precludes definitive conclusions. (C) 2021 by the American Academy of Ophthalmology
C1 [Nanji, Keean; Chaudhary, Varun] McMaster Univ, Dept Surg, Div Ophthalmol, Hamilton, ON, Canada.
   [Sarohia, Gurkaran S.] Univ Alberta, Dept Ophthalmol & Visual Sci, Edmonton, AB, Canada.
   [Kennedy, Kevin; Phillips, Mark; Thabane, Lehana; Bhandari, Mohit; Chaudhary, Varun] McMaster Univ, Dept Hlth Res Methods Evidence & Impact, Hamilton, ON, Canada.
   [Ceyhan, Tiandra] Queens Univ, Dept Ophthalmol, Kingston, ON, Canada.
   [McKechnie, Tyler] McMaster Univ, Dept Surg, Div Gen Surg, Hamilton, ON, Canada.
   [Devji, Tahira] Univ Toronto, Temerty Fac Med, Toronto, ON, Canada.
   [Kaiser, Peter] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.
   [Sarraf, David] Univ Calif Los Angeles, Stein Eye Inst, Retinal Disorders & Ophthalm Genet, Los Angeles, CA USA.
   [Garg, Sunir J.] Wills Eye Hosp & Res Inst, Retina Serv, Philadelphia, PA USA.
   [Sivaprasad, Sobha] Moorfields Eye Hosp, NIHR Moorfields Biomed Res Ctr, London, England.
   [Wykoff, Charles C.] Houston Methodist Hosp, Texas & Blanton Eye Inst, Houston, TX 77030 USA.
   [Wykoff, Charles C.] Weill Cornell Med Coll, Houston, TX USA.
   [Bakri, Sophie J.] Mayo Clin, Dept Ophthalmol, Rochester, MN USA.
   [Sheidow, Tom] Univ Western Ontario, Ivey Eye Inst, Dept Ophthalmol, London, ON, Canada.
   [Bhandari, Mohit] McMaster Univ, Dept Surg, Div Orthoped Surg, Hamilton, ON, Canada.
C3 McMaster University; University of Alberta; McMaster University; Queens
   University - Canada; McMaster University; University of Toronto;
   Cleveland Clinic Foundation; University of California System; University
   of California Los Angeles; Jefferson University; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   The Methodist Hospital System; The Methodist Hospital - Houston; Cornell
   University; Mayo Clinic; Western University (University of Western
   Ontario); McMaster University
RP Chaudhary, V (通讯作者)，St Josephs Healthcare, Hamilton Reg Eye Inst, Hamilton King Campus,2757 King St East,Room 2500, Hamilton, ON L8G 5E4, Canada.
EM vchaudh@mcmaster.ca
RI Chaudhary, Varun/AAQ-2371-2021
OI Chaudhary, Varun/0000-0002-9988-4146; Nanji, Keean/0000-0002-7176-6631;
   McKechnie, Tyler/0000-0002-7668-4096; Phillips,
   Mark/0000-0003-0923-261X; Sivaprasad, Sobha/0000-0001-8952-0659;
   Kennedy, Kevin/0000-0001-8230-091X; Sarohia,
   Gurkaran/0000-0003-2102-9518
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NR 71
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAY
PY 2022
VL 129
IS 5
BP 498
EP 508
DI 10.1016/j.ophtha.2021.11.024
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 0Z8NA
UT WOS:000791327000009
PM 34871637
DA 2022-11-30
ER

PT J
AU Ntjam, NN
   Thulliez, M
   Paintaud, G
   Salvo, F
   Angoulvant, D
   Pisella, PJ
   Bejan-Angoulvant, T
AF Ngo Ntjam, Nadege
   Thulliez, Marie
   Paintaud, Gilles
   Salvo, Francesco
   Angoulvant, Denis
   Pisella, Pierre-Jean
   Bejan-Angoulvant, Theodora
TI Cardiovascular Adverse Events With Intravitreal Anti-Vascular
   Endothelial Growth Factor Drugs A Systematic Review and Meta-analysis of
   Randomized Clinical Trials
SO JAMA OPHTHALMOLOGY
LA English
DT Review
ID RETINAL VEIN OCCLUSION; DIABETIC MACULAR EDEMA; VEGF TRAP-EYE;
   RANIBIZUMAB-MONOTHERAPY; CANCER-PATIENTS; PANRETINAL PHOTOCOAGULATION;
   AFLIBERCEPT INJECTION; BEVACIZUMAB; LASER; DEGENERATION
AB IMPORTANCE Systemic safety of intravitreal anti-vascular endothelial growth factor (anti-VEGF) is a matter of debate and regular updates are necessary.
   OBJECTIVE To evaluate systemic adverse events (SAEs) associated with intravitreal anti-VEGF drugs compared with non-anti-VEGF treatments in patients with ocular diseases.
   DATA SOURCES Electronic searches were conducted in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases from inception to July 7, 2020.
   STUDY SELECTION Randomized clinical trials conducted in adults with retinal diseases who received intravitreal anti-VEGF drugs.
   DATA EXTRACTION AND SYNTHESIS Studies and treatment characteristics and outcome data were extracted and analyzed, and study quality was evaluated.
   MAIN OUTCOMES AND MEASURES Main outcomeswere major cardiovascular events (MACEs) and total mortality. Secondary outcomes included nonocular hemorrhage, components of MACEs, other cardiovascular outcomes, serious SAEs, and all SAEs.
   RESULTS A total of 74 randomized clinical trials were analyzed: 32 trials (43%) included 14 190 patients with age-related macular degeneration (AMD), 24 (32%) included 5424 patients with diabetic retinopathy (diabetic macular edema or proliferative diabetic retinopathy), 17 trials (23%) included 3757 patients with retinal vein occlusion, and 1 trial (1%) included 122 patients withmyopic choroidal neovascularization. Anti-VEGF drug administration did not increase MACEs compared with control agents (odds ratio [OR], 1.16; 95% CI, 0.85-1.58) or total mortality (OR, 1.27; 95% CI, 0.82-1.96). There was an interaction (subgroup difference, P =.04) in mortality risk depending on the underlying disease with an increase (OR, 1.80; 95% CI, 1.03-3.16; P =.04) in the risk of death in patients with diabetic retinopathy; however, no increase was observed in patients with AMD or retinal vein occlusion. Administration of anti-VEGF drugs increased the risk of nonocular hemorrhage (OR, 1.46; 95% CI, 1.01-2.10), mainly in patients with AMD.
   CONCLUSIONS AND RELEVANCE Intravitreal anti-VEGF was not associated with an increase in MACEs in the trials examined herein. Increased mortality in patients with diabetes and nonocular hemorrhages, especially in those with AMD, could represent a safety signal, but the evidence was not strong. However, continued surveillance of SAEs remains warranted.
C1 [Ngo Ntjam, Nadege; Paintaud, Gilles; Bejan-Angoulvant, Theodora] CHRU Tours, Med Pharmacol Dept, 2 Bd Tonnelle, F-37000 Tours, France.
   [Ngo Ntjam, Nadege] CHRU Tours, Hosp Pharm, Tours, France.
   [Ngo Ntjam, Nadege; Paintaud, Gilles; Angoulvant, Denis; Bejan-Angoulvant, Theodora] Univ Tours, EA 4245, Transplantat Immun & Inflammat T2I, Tours, France.
   [Thulliez, Marie] CHU Montpellier, Ophthalmol Dept, Montpellier, France.
   [Salvo, Francesco] CHU Pellegrin, Med Pharmacol Dept, Bordeaux, France.
   [Salvo, Francesco] Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, U1219, Bordeaux, France.
   [Angoulvant, Denis] CHRU Tours, Cardiol Dept, Tours, France.
   [Pisella, Pierre-Jean] CHRU Tours, Ophthalmol Dept, Tours, France.
C3 CHU Tours; CHU Tours; Universite de Tours; Universite de Montpellier;
   CHU de Montpellier; CHU Bordeaux; UDICE-French Research Universities;
   Universite de Bordeaux; CHU Tours; CHU Tours
RP Bejan-Angoulvant, T (通讯作者)，CHRU Tours, Med Pharmacol Dept, 2 Bd Tonnelle, F-37000 Tours, France.
EM theodora.angoulvant@univ-tours.fr
RI Angoulvant, Denis/Q-9743-2019
OI Angoulvant, Denis/0000-0003-0788-8092
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NR 71
TC 6
Z9 6
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD JUN
PY 2021
VL 139
IS 6
BP 610
EP 619
DI 10.1001/jamaophthalmol.2021.0640
EA APR 2021
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA SU3EJ
UT WOS:000640630300004
PM 33856414
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Ludwig, CA
   Vail, D
   Callaway, NF
   Pasricha, MV
   Moshfeghi, DM
AF Ludwig, Cassie A.
   Vail, Daniel
   Callaway, Natalia F.
   Pasricha, Malini, V
   Moshfeghi, Darius M.
TI Pentosan Polysulfate Sodium Exposure and Drug-Induced Maculopathy in
   Commercially Insured Patients in the United States
SO OPHTHALMOLOGY
LA English
DT Article
AB Purpose: To determine the association and cumulative dose-response pattern between pentosan poly-sulfate sodium (PPS) use for interstitial cystitis (IC) and maculopathy.
   Design: Large, multicenter, retrospective cohort study of commercially insured patients in the MarketScan database (Truven Health Analytics, San Jose, CA).
   Participants: Two hundred twenty-seven thousand three hundred twenty-five patients with IC who were enrolled continuously in the MarketScan database.
   Methods: Cox proportional hazards models (controlling for patient gender, age at index diagnosis of IC, and diagnosis with diabetes mellitus) followed up patients from index diagnosis of IC for 5 years, or until patients discontinued insurance coverage, or until patients' first diagnosis with a maculopathy. As a sensitivity analysis, we re-estimate all models after excluding all patients with diabetes. To assess for dose response, we calculated the total days of PPS prescriptions filled and created a categorical variable indicating total exposure.
   Main Outcome Measures: The primary outcome measure was association between binary PPS exposure and any maculopathy. Secondary outcome measures included exposure between binary and categorical, time-dependent, exposure to PPS and to drusen, nonexudative age-related macular degeneration (AMD), exudative AMD, hereditary maculopathy, and toxic maculopathy.
   Results: The most common diagnoses of maculopathy in patients with IC were exudative AMD (1.5%), drusen (0.8%), nonexudative AMD (0.3%), toxic maculopathy (0.1 %), and hereditary dystrophy (0.04%). In unadjusted analyses, the percentage of patients who filled a PPS prescription and were diagnosed later with a maculopathy (2.37%) was very similar to the percentage of patients who did not fill a prescription (2.77%). Survival models using a binary variable indicating PPS exposure showed no significant associations between PPS exposure and diagnosis of drusen, nonexudative AMD, exudative AMD, toxic maculopathy, hereditary dystrophy, or an aggregate variable of any maculopathy. Similarly, there was no dose-dependent relationship between PPS exposure and diagnosis of any maculopathy. These findings remained stable in sensitivity analysis models that excluded patients with diabetes mellitus.
   Conclusions: In this large, commercial claims database analysis, no association was found between PPS exposure and subsequent diagnosis of maculopathy. (C) 2019 by the American Academy of Ophthalmology
C1 [Ludwig, Cassie A.; Vail, Daniel; Callaway, Natalia F.; Pasricha, Malini, V; Moshfeghi, Darius M.] Stanford Univ, Byers Eye Inst, Dept Ophthalmol, Palo Alto, CA 94303 USA.
C3 Stanford University
RP Moshfeghi, DM (通讯作者)，Stanford Univ, Byers Eye Inst, Dept Ophthalmol, Sch Med, 2452 Watson Court, Palo Alto, CA 94303 USA.
EM dariusm@stanford.edu
RI Ludwig, Cassie/AAM-3634-2020
OI Moshfeghi, Darius Mohammad/0000-0003-2254-292X; Ludwig, Cassie
   A/0000-0002-9586-3735
FU Heed Ophthalmic Foundation
FX Supported by the Heed Ophthalmic Foundation (N.F.C.).
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NR 14
TC 22
Z9 22
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD APR
PY 2020
VL 127
IS 4
BP 535
EP 543
DI 10.1016/j.ophtha.2019.10.036
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KW0VD
UT WOS:000520890400026
PM 31899034
DA 2022-11-30
ER

PT J
AU Goodman, PJ
   Tangen, CM
   Darke, AK
   Arnold, KB
   Hartline, J
   Yee, M
   Anderson, K
   Caban-Holt, A
   Christen, WG
   Cassano, PA
   Lance, P
   Klein, EA
   Crowley, JJ
   Minasian, LM
   Meyskens, FL
AF Goodman, Phyllis J.
   Tangen, Catherine M.
   Darke, Amy K.
   Arnold, Kathryn B.
   Hartline, JoAnn
   Yee, Monica
   Anderson, Karen
   Caban-Holt, Allison
   Christen, William G.
   Cassano, Patricia A.
   Lance, Peter
   Klein, Eric A.
   Crowley, John J.
   Minasian, Lori M.
   Meyskens, Frank L.
TI Opportunities and challenges in incorporating ancillary studies into a
   cancer prevention randomized clinical trial
SO TRIALS
LA English
DT Article
DE Prostate cancer; Ancillary studies; Randomized controlled trial; Study
   implementation
ID VITAMIN-E; ALZHEIMERS-DISEASE; PROSTATE-CANCER; SELENIUM; SELECT;
   DEMENTIA; RISK
AB Background: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled, prostate cancer prevention study funded by the National Cancer Institute and conducted by SWOG (Southwest Oncology Group). A total of 35,533 men were assigned randomly to one of four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, placebo + placebo). At the time of the trial's development, NIH had invested substantial resources in evaluating the potential benefits of these antioxidants. To capitalize on the knowledge gained from following a large cohort of healthy, aging males on the effects of selenium and/or vitamin E, ancillary studies with other disease endpoints were solicited.
   Methods: Four ancillary studies were added. Each drew from the same population but had independent objectives and an endpoint other than prostate cancer. These studies fell into two categories: those prospectively enrolling and following participants (studies of Alzheimer's disease and respiratory function) and those requiring a retrospective medical record review after a reported event (cataracts/age-related macular degeneration and colorectal screening). An examination of the challenges and opportunities of adding ancillary studies is provided. The impact of the ancillary studies on adherence to SELECT was evaluated using a Cox proportional hazards model.
   Results: While the addition of ancillary studies appears to have improved participant adherence to the primary trial, this did not come without added complexity. Activation of the ancillary studies happened after the SELECT randomizations had begun resulting in accrual problems to some of the studies. Study site participation in the ancillary trials varied greatly and depended on the interest of the study site principal investigator. Procedures for each were integrated into the primary trial and all monitoring was done by the SELECT Data and Safety Monitoring Committee. The impact of the early closure of the primary trial was different for each of the ancillary trials.
   Conclusions: The ancillary studies allowed study sites to broaden the research opportunities for their participants. Their implementation was efficient because of the established infrastructure of the primary trial. Implementation of these ancillary trials took substantial planning and coordination but enriched the overall primary trial.
C1 [Goodman, Phyllis J.; Tangen, Catherine M.; Darke, Amy K.; Arnold, Kathryn B.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1100 Fairview Ave N,M3-C102, Seattle, WA 98109 USA.
   [Hartline, JoAnn; Yee, Monica; Anderson, Karen; Crowley, John J.] SWOG Stat Ctr, Canc Res & Biostat, Seattle, WA USA.
   [Caban-Holt, Allison] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
   [Christen, William G.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
   [Cassano, Patricia A.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
   [Lance, Peter] Univ Arizona, Arizona Canc Ctr, Phoenix, AZ USA.
   [Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
   [Minasian, Lori M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
   [Meyskens, Frank L.] Univ Calif Irvine, Orange, CA 92668 USA.
C3 Fred Hutchinson Cancer Center; Southwest Oncology Group; Cancer Research
   & Biostatistics; Southwest Oncology Group; University of Kentucky;
   Harvard University; Brigham & Women's Hospital; Harvard Medical School;
   Cornell University; Arizona Center Cancer Care; University of Arizona;
   Cleveland Clinic Foundation; National Institutes of Health (NIH) - USA;
   NIH National Cancer Institute (NCI); University of California System;
   University of California Irvine
RP Goodman, PJ (通讯作者)，Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1100 Fairview Ave N,M3-C102, Seattle, WA 98109 USA.
EM pgoodman@fredhutch.org
OI Cassano, Patricia A./0000-0003-4827-5073; Darke,
   Amy/0000-0002-9821-2065; Klein, Eric A/0000-0002-1783-0698
FU Public Health Service - National Cancer Institute, National Institutes
   of Health, Department of Health and Human Services [CA37429, UM1
   CA182883]; National Center for Complementary and Alternative Medicine
   (National Institutes of Health); NIA [R01 AG19241]; NEI [EY014418];
   NHLBI [RO1HL071022]; NCI [R01CA124862]; NATIONAL CANCER INSTITUTE
   [R01CA124862, UM1CA182883, U10CA037429, UG1CA189974] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R01EY014418] Funding Source: NIH
   RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL071022]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGING [R01AG019241]
   Funding Source: NIH RePORTER
FX This work was supported in part by Public Health Service Cooperative
   Agreement grant CA37429 and UM1 CA182883 awarded by the National Cancer
   Institute, National Institutes of Health, Department of Health and Human
   Services, and in part by the National Center for Complementary and
   Alternative Medicine (National Institutes of Health). It was also
   supported in part by NIA R01 AG19241 (PREADVISE), NEI EY014418 (SEE),
   NHLBI (RO1HL071022) (RAS) and NCI R01CA124862 (ACP). Study agents and
   packaging were provided by Perrigo Company (Allegan, MI, USA), Sabinsa
   Corporation (Piscataway, NJ, USA), Tishcon Corporation (Westbury, NY,
   USA) and DSM Nutritional Products Inc. (Parsipanny, NJ, USA).
CR Buschke H, 1999, NEUROLOGY, V52, P231, DOI 10.1212/WNL.52.2.231
   Cassano PA, 2015, RESP RES, V16, DOI 10.1186/s12931-015-0195-5
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   Klein EA, 2011, JAMA-J AM MED ASSOC, V306, P1549, DOI 10.1001/jama.2011.1437
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NR 12
TC 0
Z9 0
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD AUG 12
PY 2016
VL 17
AR 400
DI 10.1186/s13063-016-1524-9
PG 10
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA DT2ZE
UT WOS:000381349500001
PM 27519183
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kim, JH
   Chang, YS
   Kim, JW
   Kim, CG
   Yoo, SJ
   Cho, HJ
AF Kim, Jae Hui
   Chang, Young Suk
   Kim, Jong Woo
   Kim, Chul Gu
   Yoo, Su Jin
   Cho, Han Ju
TI Intravitreal Anti-Vascular Endothelial Growth Factor for Submacular
   Hemorrhage from Choroidal Neovascularization
SO OPHTHALMOLOGY
LA English
DT Article
ID TISSUE-PLASMINOGEN ACTIVATOR; MACULAR DEGENERATION; SUBRETINAL
   HEMORRHAGE; PNEUMATIC DISPLACEMENT; PHOTODYNAMIC THERAPY; BEVACIZUMAB
   AVASTIN; FACTOR MONOTHERAPY; SURGICAL REMOVAL; NATURAL-HISTORY;
   RANIBIZUMAB
AB Purpose: To evaluate the efficacy of intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy for patients diagnosed with exudative age-related macular degeneration (AMD) accompanied by submacular hemorrhage.
   Design: Retrospective, observational case series.
   Participants: Ninety-one eyes of 91 patients who initially presented with submacular hemorrhage associated with exudative AMD from October 2009 to September 2012. Patients were followed up for at least 6 months after treatment.
   Methods: Best-corrected visual acuity (BCVA) was measured at diagnosis and at 1, 3, and 6 months after treatment. The duration of symptoms was estimated. The extent of hemorrhage was estimated using fundus photography, and central foveal thickness was measured using optical coherence tomography. Change in BCVA during 6 months after treatment was estimated. The correlation of BCVA at 6 months with duration of symptoms, extent of hemorrhage, and central foveal thickness was evaluated.
   Main Outcome Measures: The BCVA, duration of symptoms, extent of hemorrhage, and central foveal thickness.
   Results: The mean duration of symptoms was 27.6 +/- 39.5 days. The mean extent of hemorrhage was 7.8 +/- 5.6 disc areas, and the mean central foveal thickness was 610.1 +/- 249.6 mm. All eyes were treated with 3.2 +/- 0.8 (range, 1-5) monthly intravitreal anti-VEGF injections during the 6-month follow-up period. The logarithm of the minimum angle of resolution BCVA at diagnosis and at 1, 3, and 6 months after the initial diagnosis was 1.38 +/- 0.53 (Snellen equivalent, 20/ 479), 1.27 +/- 0.57, 1.05 +/- 0.58, and 0.96 +/- 0.65 (Snellen equivalent, 20/182), respectively. The BCVA at 6 months significantly improved from baseline (P < 0.001). Poor BCVA at 6 months correlated with a longer duration of symptoms, greater extent of hemorrhage, and greater central foveal thickness (P = 0.008, P = 0.004, and P = 0.014, respectively).
   Conclusions: Anti-VEGF monotherapy was found to be a useful treatment option for exudative AMD accompanied by submacular hemorrhage. However, the limited efficacy in eyes with large hemorrhage may suggest the need for more aggressive treatment in these cases. Ophthalmology 2014;121:926-935 (C) 2014 by the American Academy of Ophthalmology.
C1 [Kim, Jae Hui; Chang, Young Suk; Kim, Jong Woo; Kim, Chul Gu; Yoo, Su Jin; Cho, Han Ju] Konyang Univ, Kims Eye Hosp, Coll Med, Dept Ophthalmol, Seoul, South Korea.
C3 Konyang University; Konyang University Hospital
RP Kim, JH (通讯作者)，Kims Eye Hosp, Dept Ophthalmol, 156 Youngdeungpo Dong 4ga, Seoul 150034, South Korea.
EM kimoph@gmail.com
OI Cho, Han Joo/0000-0001-7336-5762
CR Ahmad S, 2008, AM J OPHTHALMOL, V145, P1052, DOI 10.1016/j.ajo.2008.02.008
   Arias L, 2009, EYE, V23, P326, DOI 10.1038/sj.eye.6703053
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   Spaide RF, 2006, RETINA-J RET VIT DIS, V26, P383, DOI 10.1097/00006982-200604000-00001
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NR 31
TC 57
Z9 58
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD APR
PY 2014
VL 121
IS 4
BP 926
EP 935
DI 10.1016/j.ophtha.2013.11.004
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AE2MV
UT WOS:000333808100025
PM 24342019
DA 2022-11-30
ER

PT J
AU Mrejen, S
   Sato, T
   Curcio, CA
   Spaide, RF
AF Mrejen, Sarah
   Sato, Taku
   Curcio, Christine A.
   Spaide, Richard F.
TI Assessing the Cone Photoreceptor Mosaic in Eyes with Pseudodrusen and
   Soft Drusen In Vivo Using Adaptive Optics Imaging
SO OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; RETICULAR PSEUDODRUSEN;
   COHERENCE TOMOGRAPHY; DEPOSITS; PREVALENCE; RETINA; PROGRESSION; ATROPHY
AB Purpose: To investigate the cone photoreceptor mosaic in eyes with pseudodrusen as evidenced by the presence of subretinal drusenoid deposits (SDD) and conventional drusen using adaptive optics (AO) imaging integrated into a multimodal imaging approach.
   Design: Observational case series.
   Participants: Eleven patients (11 eyes) with pseudodrusen and 6 patients (11 eyes) with conventional drusen.
   Methods: Consecutive patients were examined using near-infrared reflectance (IR) confocal scanning laser ophthalmoscopy (SLO) and eye-tracked spectral-domain optical coherence tomography (SD-OCT) and floodilluminated retinal AO camera of nonconfluent pseudodrusen or conventional drusen. Correlations were made between the IR-SLO, SD-OCT, and AO images. Cone density analysis was performed on AO images within 50 +/- 50-mm windows in 5 regions of interest overlying and in 5 located between SDD or conventional drusen with the same retinal eccentricity.
   Main Outcome Measures: Cone densities in the regions of interest.
   Results: The pseudodrusen correlated with subretinal accumulations of material in SD-OCT imaging and this was confirmed in the AO images. Defects in the overlying ellipsoid zone band as seen by SD-OCT were associated with SDD but not conventional drusen. The mean +/- standard deviation cone density was 8964 +/- 2793 cones/mm(2) between the SDD and 863 +/- 388 cones/mm(2) over the SDD, a 90.4% numerical reduction. By comparison the mean cone packing density was 9838 +/- 3723 cones/mm(2) on conventional drusen and 12 595 +/- 3323) cones/mm(2) between them, a 21.9% numerical reduction. The difference in cone density reduction between the two lesion types was highly significant (P< 0.001).
   Conclusions: The pseudodrusen in these eyes correlated with subretinal deposition of material in multiple imaging modalities. Reduced visibility of cones overlying SDD in the AO images can be because of several possible causes, including a change in their orientation, an alteration of their cellular architecture, or absence of the cones themselves. All of these explanations imply that decreased cone photoreceptor function is possible, suggesting that eyes with pseudodrusen appearance may experience decreased retinal function in age-related macular degeneration independent of choroidal neovascularization or retinal pigment epithelial atrophy. (C) 2014 by the American Academy of Ophthalmology.
C1 [Mrejen, Sarah; Sato, Taku; Spaide, Richard F.] Vitreous Retina Macula Consultants New York, New York, NY 10022 USA.
   [Mrejen, Sarah; Sato, Taku; Spaide, Richard F.] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY USA.
   [Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL 35294 USA.
C3 Vitreous Retina Macula Consultants of New York; Manhattan Eye Ear &
   Throat Hospital; University of Alabama System; University of Alabama
   Birmingham
RP Spaide, RF (通讯作者)，Vitreous Retina Macula Consultants New York, 460 Pk Ave,Fifth Floor, New York, NY 10022 USA.
EM rick.spaide@gmail.com
RI Spaide, Richard/ABD-7368-2020; Mrejen, Sarah/G-2089-2016
FU LuEsther T. Mertz Retinal Research Foundation; EyeSight Foundation of
   Alabama and Research to Prevent Blindness Inc. [NEI EY06109]; NATIONAL
   EYE INSTITUTE [R01EY006109] Funding Source: NIH RePORTER
FX Supported by the LuEsther T. Mertz Retinal Research Foundation. C.A.C.
   is supported by NEI EY06109 with institutional support from the EyeSight
   Foundation of Alabama and Research to Prevent Blindness Inc.
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NR 27
TC 62
Z9 63
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD FEB
PY 2014
VL 121
IS 2
BP 545
EP 551
DI 10.1016/j.ophtha.2013.09.026
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 302CO
UT WOS:000330579200020
PM 24183341
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Milani, P
   Massacesi, A
   Setaccioli, M
   Moschini, S
   Mantovani, E
   Ciaccia, S
   Bergamini, F
AF Milani, Paolo
   Massacesi, Amedeo
   Setaccioli, Marco
   Moschini, Stefania
   Mantovani, Elena
   Ciaccia, Stefano
   Bergamini, Fulvio
TI Sensitivity of fluorescein angiography alone or with SD-OCT for the
   diagnosis of myopic choroidal neovascularization
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE OCT; Spectral-domain OCT; Spectralis; CNV; Fluorescein angiography;
   Myopia; Pathologic myopia; Diagnosis sensitivity
ID OPTICAL COHERENCE TOMOGRAPHY; INDOCYANINE GREEN ANGIOGRAPHY;
   PATHOLOGICAL MYOPIA; MACULAR DEGENERATION; AGE; FEATURES
AB Myopic choroidal neovascularization (mCNV) has certain characteristics and features that distinguish it from choroidal neovascularization secondary to age-related macular degeneration. There may be angiographic diagnostic difficulties even when using the scanning laser ophthalmoscope, which gives more contrast and better definition than traditional angiography. The aim of the study is to compare the sensitivity of fluorescein angiography (FA) alone or combined with Spectral Domain Optical Coherence Tomography (SD-OCT) for assessing the incidence of mCNV.
   In this retrospective study, two authors reviewed the charts and images of patients with recent (< 30 days) vision deterioration, pathologic myopia, axial length > 26 mm, documentation or suspicion of mCNV or macular exudative pathologies at FA and OCT. They only examined the images at first presentation obtained by the multi-modal imaging system that combines Infrared reflectance, FA, and SD-OCT, (Spectralis, Heidelberg Engineering, Germany). The images selected were then evaluated by three other investigators in blinded, independent conditions, in order to make their diagnosis, which was noted or rated as doubtful if it could not be decided on the basis of FA alone. SD-OCT images were then shown and compared to IR and FA by each of the three investigators individually to formulate a conclusive diagnosis.
   A total of 71 eyes of 69 patients were suitable for the study, mean age 65.97 +/- 14.57 years, spherical equivalent refraction -8.82 +/- A 2.51 diopters. Concordance between the three examiners' interpretations of FA features and FA-guided SD-OCT was 50/71 (70.4 %) and 67/71 (94 %) respectively. Total agreement on diagnosis between the three examiners was achieved in 55 % of cases for FA (kappa = 0.53, p < 0.001), and 94 % for FA-guided SD-OCT (k = -0.01, p = 0.5). The final diagnosis with FA and FA-guided SD-OCT differed in 29 cases (40 %; 95 % C.I. 29-42 %), whereas 12 (17 %) mCNV were overlooked at FA, and in 11 (15 %) cases none of the examiners reached a diagnosis based on FA alone.
   On the basis of FA alone, active mCNV can be misdiagnosed. The use of SD-OCT combined with FA should therefore be strongly considered.
C1 [Milani, Paolo; Massacesi, Amedeo; Setaccioli, Marco; Moschini, Stefania; Mantovani, Elena; Ciaccia, Stefano; Bergamini, Fulvio] Ist Auxol, Milan, Italy.
C3 IRCCS Istituto Auxologico Italiano
RP Milani, P (通讯作者)，Via Stefini 10, I-20125 Milan, Italy.
EM dottpaolomilani@hotmail.com
OI Setaccioli, Marco/0000-0002-0500-8728; Milani, Paolo/0000-0002-0409-6201
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NR 26
TC 11
Z9 11
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD AUG
PY 2013
VL 251
IS 8
BP 1891
EP 1900
DI 10.1007/s00417-013-2282-y
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 196PE
UT WOS:000322786900003
PM 23436079
DA 2022-11-30
ER

PT J
AU Glittenberg, C
   Binder, S
AF Glittenberg, C.
   Binder, S.
TI Results of the ICAPE pilot study: Interactive computer aided patient
   education pilot study
SO SPEKTRUM DER AUGENHEILKUNDE
LA English
DT Article
ID FUNCTIONAL HEALTH LITERACY; RANDOMIZED-TRIAL; GLAUCOMA; SURGERY
AB PURPOSE: To report about the results of the ICAPE (Interactive Computer Aided Patient Education) Pilot Study. STUDY DESIGN: Evaluation of a new technology. METHODS: 144 participants, consisting of 20 patients about to undergo cataract surgery (Group 1), 18 ophthalmologists and ophthalmic registered nurses (Group 2), 18 medical interns (Group 3), and 88 lay-persons (group 4) were shown varying interactive computer animations from the 3D-Eye-Office (TM) (Eyemaginations (TM)) software package which lasted between 4 minutes (Group 1) and 2 hours (Group 2). These videos explained the physiology and the anatomy of the human visual system, as well as the patho-physiology of myopia, hyperopia, cataracts, diabetic retinopathy, age related macular degeneration, retinal detachment, retinal tears, and glaucoma. They also explained in depth the ophthalmic surgical procedures relating to these diseases and the possible risks and complications. After the participants had viewed the videos, they were asked to fill out questionnaires relating to the quality and usefulness of the videos. RESULTS: 144 participants were asked to answer a total of 1254 questions about a total of 9 ophthalmic subjects taught to them using the 3D-Eye Office (TM) patient education system. The results of the questionnaires showed overwhelming approval of the quality of the videos from all participant groups. If the results from Groups 1 and 4 are added togethe and expressed as a percentage, the average approval rating for the videos from patients is 92.7%. If the results from Groups 2 and 3 are added together and expressed as a percentage, the average approval rating for the videos from medical professionals is 88.9%. CONCLUSION: The 3D-Eye Office (TM) system is a clear and concise method of educating patients about complex subjects in ophthalmology. However, the system should not be used as a replacement for the standard informed consent process, but rather as a precursor to it. This may help to streamline the informed consent process. The 3D-Eye Office (TM) system could also be very useful in the education of student nurses and non-ophthalmic medical professionals. These points need to be verified in a larger multi center study.
C1 [Glittenberg, C.; Binder, S.] Rudolf Fdn Clin, Dept Ophthalmol, A-1030 Vienna, Austria.
   [Glittenberg, C.; Binder, S.] Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, Vienna, Austria.
C3 Ludwig Boltzmann Institute
RP Glittenberg, C (通讯作者)，Rudolf Fdn Clin, Dept Ophthalmol, Juchgasse 25, A-1030 Vienna, Austria.
EM carl.glittenberg@wienkav.at
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NR 22
TC 0
Z9 0
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0930-4282
J9 SPEKTRUM AUGENHEILKD
JI Spektrum Augenheilkd.
PD DEC
PY 2008
VL 22
IS 6
BP 376
EP 383
DI 10.1007/s00717-008-0301-x
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 394XB
UT WOS:000262485400008
DA 2022-11-30
ER

PT J
AU Hubbard, LD
   Danis, RP
   Neider, MW
   Thayer, DW
   Wabers, HD
   White, JK
   Pugliese, AJ
   Pugliese, MF
AF Hubbard, Larry D.
   Danis, Ronald P.
   Neider, Michael W.
   Thayer, Dennis W.
   Wabers, Hugh D.
   White, James K.
   Pugliese, Anthony J.
   Pugliese, Michael F.
CA Age-Related Eye Dis Res Grp
TI Brightness, contrast, and color balance of digital versus film retinal
   images in the age-related eye disease study 2
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY
AB PURPOSE. To analyze brightness, contrast, and color balance of digital versus film retinal images in a multicenter clinical trial, to propose a model image from exemplars, and to optimize both image types for evaluation of age-related macular degeneration (AMD).
   METHODS. The Age-Related Eye Disease Study 2 (AREDS2) is enrolling subjects from 90 clinics, with three quarters of them using digital and one quarter using film cameras. Image brightness (B), contrast (C), and color balance (CB) were measured with three-color luminance histograms. First, the exemplars (film and digital) from expert groups were analyzed, and an AMD-oriented model was constructed. Second, the impact of B/C/CB on the appearance of typical AMD abnormalities was analyzed. Third, B/C/CB in AREDS2 images were compared between film (156 eyes) and digital (605 eyes), and against the model. Fourth, suboptimal images were enhanced by adjusting B/C/CB to bring them into accord with model parameters.
   RESULTS. Exemplar images had similar brightness, contrast, and color balance, supporting an image model. Varying a specimen image through a wide range of B/C/CB revealed greatest contrast of drusen and pigment abnormalities against normal retinal pigment epithelium with the model parameters. AREDS2 digital images were more variable than film, with lower correspondence to our model. Ten percent of digital were too dim and 19% too bright (oversaturated), versus 1% and 4% of film, respectively. On average, digital had lower green channel contrast (giving less retinal detail) than film. Overly red color balance (weaker green) was observed in 23% of digital versus 8% of film. About half of digital (but fewer film) images required enhancement before AMD grading. After optimization of both image types, AREDS2 image quality was judged as good as that in AREDS (all film).
   CONCLUSIONS. A histogram-based model, derived from exemplars, provides a pragmatic guide for image analysis and enhancement. In AREDS2, the best digital images matched the best film. Overall, however, digital provided lower contrast of retinal detail. Digital images taken with higher G-to-R ratio showed better brightness and contrast management. Optimization of images in the multicenter study helps standardize documentation of AMD (ClinicalTrials. gov NCT00345176).
C1 [Hubbard, Larry D.; Danis, Ronald P.; Neider, Michael W.; Thayer, Dennis W.; Wabers, Hugh D.; White, James K.] Univ Wisconsin, Fundus Photograph Reading Ctr, Dept Ophthalmol & Visual Sci, Madison, WI 53711 USA.
   [Pugliese, Anthony J.; Pugliese, Michael F.] Choices Serv Imaging Inc, Glen Rock, NJ USA.
C3 University of Wisconsin System; University of Wisconsin Madison
RP Hubbard, LD (通讯作者)，Univ Wisconsin, Fundus Photograph Reading Ctr, Dept Ophthalmol & Visual Sci, 406 Sci Dr,Suite 400, Madison, WI 53711 USA.
EM hubbard@rc.ophth.wisc.edu
FU PHS HHS [HHSN 260-2006-00003C] Funding Source: Medline
CR Age-Related Eye Dis Study Res Grp, 2001, AM J OPHTHALMOL, V132, P668
   Davis MD, 2005, ARCH OPHTHALMOL-CHIC, V123, P1484
   Klein R, 2004, ARCH OPHTHALMOL-CHIC, V122, P1642, DOI 10.1001/archopht.122.11.1642
   Klein R, 2002, OPHTHALMOLOGY, V109, P1767, DOI 10.1016/S0161-6420(02)01146-6
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NR 9
TC 55
Z9 57
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2008
VL 49
IS 8
BP 3269
EP 3282
DI 10.1167/iovs.07-1267
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 330NW
UT WOS:000257951100003
PM 18421079
DA 2022-11-30
ER

PT J
AU Li, B
   Chen, H
   Zhang, BL
   Yuan, MZ
   Jin, XM
   Lei, B
   Xu, J
   Gu, W
   Wong, DCS
   He, XX
   Wang, H
   Ding, DY
   Li, XR
   Chen, YX
   Yu, WH
AF Li, Bing
   Chen, Huan
   Zhang, Bilei
   Yuan, Mingzhen
   Jin, Xuemin
   Lei, Bo
   Xu, Jie
   Gu, Wei
   Wong, David Chuen Soong
   He, Xixi
   Wang, Hao
   Ding, Dayong
   Li, Xirong
   Chen, Youxin
   Yu, Weihong
TI Development and evaluation of a deep learning model for the detection of
   multiple fundus diseases based on colour fundus photography
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE imaging; retina; diagnostic tests; investigation
ID RETINAL VEIN OCCLUSION; DIABETIC-RETINOPATHY; MACULAR DEGENERATION;
   GLOBAL PREVALENCE; CLASSIFICATION; VALIDATION; GLAUCOMA; IMAGES
AB Aim To explore and evaluate an appropriate deep learning system (DLS) for the detection of 12 major fundus diseases using colour fundus photography. Methods Diagnostic performance of a DLS was tested on the detection of normal fundus and 12 major fundus diseases including referable diabetic retinopathy, pathologic myopic retinal degeneration, retinal vein occlusion, retinitis pigmentosa, retinal detachment, wet and dry age-related macular degeneration, epiretinal membrane, macula hole, possible glaucomatous optic neuropathy, papilledema and optic nerve atrophy. The DLS was developed with 56 738 images and tested with 8176 images from one internal test set and two external test sets. The comparison with human doctors was also conducted. Results The area under the receiver operating characteristic curves of the DLS on the internal test set and the two external test sets were 0.950 (95% CI 0.942 to 0.957) to 0.996 (95% CI 0.994 to 0.998), 0.931 (95% CI 0.923 to 0.939) to 1.000 (95% CI 0.999 to 1.000) and 0.934 (95% CI 0.929 to 0.938) to 1.000 (95% CI 0.999 to 1.000), with sensitivities of 80.4% (95% CI 79.1% to 81.6%) to 97.3% (95% CI 96.7% to 97.8%), 64.6% (95% CI 63.0% to 66.1%) to 100% (95% CI 100% to 100%) and 68.0% (95% CI 67.1% to 68.9%) to 100% (95% CI 100% to 100%), respectively, and specificities of 89.7% (95% CI 88.8% to 90.7%) to 98.1% (95%CI 97.7% to 98.6%), 78.7% (95% CI 77.4% to 80.0%) to 99.6% (95% CI 99.4% to 99.8%) and 88.1% (95% CI 87.4% to 88.7%) to 98.7% (95% CI 98.5% to 99.0%), respectively. When compared with human doctors, the DLS obtained a higher diagnostic sensitivity but lower specificity. Conclusion The proposed DLS is effective in diagnosing normal fundus and 12 major fundus diseases, and thus has much potential for fundus diseases screening in the real world.
C1 [Li, Bing; Chen, Huan; Zhang, Bilei; Chen, Youxin; Yu, Weihong] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Ophthalmol, Beijing, Peoples R China.
   [Li, Bing; Chen, Huan; Zhang, Bilei; Chen, Youxin; Yu, Weihong] Chinese Acad Med Sci, Peking Union Mecical Coll, Key Lab Ocular Fundus Dis, Beijing, Peoples R China.
   [Yuan, Mingzhen; Xu, Jie] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Dept Ophthalmol,Beijing Inst Ophthalmol, Beijing, Peoples R China.
   [Jin, Xuemin] Zhengzhou Univ, Affiliated Hosp 1, Dept Ophthalmol, Zhengzhou, Henan, Peoples R China.
   [Lei, Bo] Henan Prov Peoples Hosp, Henan Eye Hosp, Henan Eye Inst, Clin Res Ctr, Zhengzhou, Henan, Peoples R China.
   [Gu, Wei] Beijing Aier Intech Eye Hosp, Dept Ophthalmol, Beijing, Peoples R China.
   [Wong, David Chuen Soong] Univ Cambridge, Sch Clin Med, Cambridge, England.
   [He, Xixi; Wang, Hao; Ding, Dayong] Visionary Intelligence Ltd, Vistel AI Lab, Beijing, Peoples R China.
   [Li, Xirong] Renmin Univ China, Key Lab DEKE, Beijing, Peoples R China.
C3 Chinese Academy of Medical Sciences - Peking Union Medical College;
   Peking Union Medical College Hospital; Chinese Academy of Medical
   Sciences - Peking Union Medical College; Capital Medical University;
   Zhengzhou University; Zhengzhou University; University of Cambridge;
   Renmin University of China
RP Yu, WH (通讯作者)，Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Ophthalmol, Beijing, Peoples R China.; Yu, WH (通讯作者)，Chinese Acad Med Sci, Peking Union Mecical Coll, Key Lab Ocular Fundus Dis, Beijing, Peoples R China.; Chen, YX (通讯作者)，Peking Union Med Coll Hosp, Ophthalmol, Beijing, Peoples R China.
EM chenyx@pumch.cn; 536273640@qq.com
RI Li, Xirong/AAD-3347-2019; xu, jie/GQR-1913-2022; Xu, Jie/AIE-0524-2022
OI Li, Xirong/0000-0002-0220-8310; xu, jie/0000-0002-2039-7055; Wong,
   David/0000-0002-1712-9527; Lei, Bo/0000-0002-5497-0905; Zhang,
   Bilei/0000-0001-9368-4939
FU CAMS Initiative for Innovative Medicine (CAMS-12M) [2018-I2M-AI-001];
   Pharmaceutical collaborative innovation research project of Beijing
   Science and Technology Commission [Z191100007719002]; Beijing Natural
   Science Foundation Haidian original innovation joint fund [19L2062];
   Natural Science Foundation of Beijing Municipality [4202033]; priming
   scientific research foundation for the junior researcher in Beijing
   Tongren Hospital, Capital Medical University [2018-YJJ-ZZL-052]
FX CAMS Initiative for Innovative Medicine (CAMS-12M)(2018-I2M-AI-001).
   Pharmaceutical collaborative innovation research project of Beijing
   Science and Technology Commission (Z191100007719002). Beijing Natural
   Science Foundation Haidian original innovation joint fund (19L2062).
   Natural Science Foundation of Beijing Municipality 4202033. The priming
   scientific research foundation for the junior researcher in Beijing
   Tongren Hospital, Capital Medical University (2018-YJJ-ZZL-052).
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NR 33
TC 9
Z9 9
U1 5
U2 23
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD AUG
PY 2022
VL 106
IS 8
BP 1079
EP 1086
DI 10.1136/bjophthalmol-2020-316290
EA MAR 2021
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3N6ON
UT WOS:000727744900001
PM 33785508
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Klettner, A
   Brinkmann, A
   Winkelmann, K
   Kackenmeister, T
   Hildebrandt, J
   Roider, J
AF Klettner, Alexa
   Brinkmann, Anna
   Winkelmann, Katrin
   Kaeckenmeister, Tom
   Hildebrandt, Julia
   Roider, Johann
TI Effect of long-term inflammation on viability and function of RPE cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retinal pigment epithelium; Inflammation; Toll-like receptors; TNF
   alpha; Lipopolysaccharide; Poly I:C; Phagocytosis; RPE65; IL-6; IL-8
ID RETINAL-PIGMENT EPITHELIUM; TOLL-LIKE RECEPTOR-3; NF-KAPPA-B; TNF-ALPHA;
   GEOGRAPHIC ATROPHY; OXIDATIVE STRESS; INNATE IMMUNITY; AMYLOID-BETA;
   IN-VITRO; ACTIVATION
AB Purpose: Degenerative ocular disorders like age-related macular degeneration (AMD) are associated with long-term pro-inflammatory signals on retinal pigment epithelial (RPE) cells. In this study, we investigated the effect of long term treatment of RPE cells with agonists of toll-like receptor (TLR) -3 (Polyinosinic:polycytidylic acid, Poly I:C), TLR-4 (lipopolysaccharide, LPS) and the pro-inflammatory cytokine TNF alpha.
   Methods: All tests were conducted with primary porcine RPE. Cells were stimulated with Poly I:C (1, 10, 100 mu g/ml), LPS (0.1, 1, 10 mu g/ml) or TNF alpha (12.5, 25 or 50 ng/ml) for 1 day, 7 days or 4 weeks. Cell viability tests (MTT) were additionally tested in ARPE-19 cells. Cytokine secretion (IL-6, IL-1 beta, IL-8, TNF alpha, TGF-beta) was tested in ELISA, phagocytosis in a microscopic assay, and expression of RPE65 in Western blot. Barrier function was tested in transwell-cultured cells by measuring transepithelial resistance for up to 3 days.
   Results: LPS and TNF alpha significantly reduce cell viability after 1 day and 7 days, Poly I:C after 7 days and 4 weeks. LPS, Poly I:C and TNF alpha significantly induce the secretion of IL-6 and IL-8 at all tested time points. IL-1 beta is increased by LPS and Poly I:C after 1 day, but not by TNF alpha. TNF alpha secretion is increased by Poly I:C and LPS after 1 day but not at later time points. TGF-beta secretion is not influenced by any stimulus. Concerning RPE function, LPS decreased phagocytosis after 7 days, while Poly I:C and TNF alpha showed no effect. RPE65 expression was strongly reduced by TNF alpha and LPS after 4 weeks. Wound healing capacity was reduced by Poly I:C but induced by LPS after 7 d and 4 w. Barrier function was not affected by Poly I:C or LPS, while TNF alpha reduced barrier function after 1 h, 4 h and 3 days.
   Conclusion: Long term pro-inflammatory stimuli reduce RPE viability, barrier properties and cellular function and induce pro-inflammatory cytokines and therefore may contribute directly to atrophic changes in AMD.
C1 [Klettner, Alexa; Brinkmann, Anna; Winkelmann, Katrin; Kaeckenmeister, Tom; Hildebrandt, Julia; Roider, Johann] Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller Str 3,Haus B2, D-24105 Kiel, Germany.
C3 University of Kiel
RP Klettner, A (通讯作者)，Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller Str 3,Haus B2, D-24105 Kiel, Germany.
EM AlexaKarina.Klettner@uksh.de
OI Klettner, Alexa/0000-0002-2709-1059
FU Dr. Jackstadt Stiftung; Hermann-Wacker foundation
FX This study was supported by the Dr. Jackstadt Stiftung and the
   Hermann-Wacker foundation. Parts of the study have been presented that
   the VII. International DOG Symposium on AMD, 2019, Baden-aden, Germany.
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PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2020
VL 200
AR 108214
DI 10.1016/j.exer.2020.108214
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OP5UI
UT WOS:000588151200014
PM 32898511
DA 2022-11-30
ER

PT J
AU Evans, RN
   Reeves, BC
   Phillips, D
   Muldrew, KA
   Rogers, C
   Harding, SP
   Chakravarthy, U
AF Evans, Rebecca N.
   Reeves, Barnaby C.
   Phillips, Dawn
   Muldrew, Katherine Alyson
   Rogers, Chris
   Harding, Simon P.
   Chakravarthy, Usha
CA IVAN Study Grp
TI Long-term Visual Outcomes after Release from Protocol in Patients who
   Participated in the Inhibition of VEGF in Age-related Choroidal
   Neovascularisation (IVAN) Trial
SO OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; RANIBIZUMAB
AB Purpose: To describe visual outcomes, frequency of treatment and monitoring visits, and anti-vascular endothelial growth factor drugs used in usual care in participants who exited a trial in which treatment for neovascular age-related macular degeneration (nAMD) was initiated with bevacizumab or ranibizumab.
   Design: Multicenter cohort study up to 7 years after trial exit.
   Participants: Patients enrolled in the Inhibition of VEGF in Age-related choroidal Neovascularisation (IVAN) trial; after excluding participants from 2 sites and who died or withdrew during the trial, 537 were included in this follow-up cohort.
   Methods: Data were collected between May 26, 2016, and August 24, 2017. Distance visual acuity (DVA) (letters read) in both eyes and treatments for nAMD administered to either eye at all usual care visits were extracted from medical records of all participants until the point of data collection (duration of study eye monitoring).
   Main Outcome Measures: Rate of change of DVA during active surveillance of the study eye (study eye monitoring), estimated using a multivariable linear random effects model. Other outcome measures were visit and treatment frequency and switches in anti-vascular endothelial growth factor (VEGF) drug.
   Results: Data were obtained for 99% (532/537) of eligible participants. The median duration of study eye monitoring after IVAN exit was 3.3 years (interquartile range [IQR], 1.3-4.7), and median DVA was 58.0 letters (IQR, 34.0-73.0). Study eye DVA deteriorated by 4.3 (95% confidence interval [CI], 3.7-4.9) letters per year. Injection rate did not influence the rate of change in DVA after adjusting for key covariates. After IVAN exit, 174 participants (32%) received no treatment; 332 of 358 (93%) were treated first with ranibizumab, 78 (23%) of whom switched to aflibercept. The DVA was similar among participants who switched or did not switch at the end of study monitoring.
   Conclusions: Approximately 5 years after the IVAN study finished, with unprecedented completeness of follow-up for such a trial, the trajectory of functional decline in the study eye was shown to be greater than that previously reported for incomplete trial cohorts. Anti-VEGF injection rates and treatment switches were not important factors in determining visual acuity outcomes. (C) 2020 by the American Academy of Ophthalmology.
C1 [Evans, Rebecca N.; Reeves, Barnaby C.; Phillips, Dawn; Rogers, Chris] Univ Bristol, Bristol Trials Ctr, Bristol Med Sch, Clin Trials & Evaluat Unit, Bristol, Avon, England.
   [Muldrew, Katherine Alyson; Chakravarthy, Usha] Queens Univ Belfast, Royal Victoria Hosp, Belfast, Antrim, North Ireland.
   [Harding, Simon P.] Univ Liverpool, Inst Ageing & Chron Dis, Dept Eye & Vis Sci, Liverpool, Merseyside, England.
C3 University of Bristol; Queens University Belfast; University of
   Liverpool
RP Chakravarthy, U (通讯作者)，Queens Univ Belfast, Ctr Publ Hlth, Belfast BT12 6BA, Antrim, North Ireland.
EM u.chakravarthy@qub.ac.uk
OI Rogers, Chris/0000-0002-9624-2615; Reeves, Barnaby/0000-0002-5101-9487;
   Evans, Rebecca/0000-0002-7119-8187; Phillips, Dawn/0000-0002-1322-472X
FU National Institute for Health Research (NIHR) UK Health Technology
   Assessment Program [07/36/01, 07/36/501]
FX The National Institute for Health Research (NIHR) UK Health Technology
   Assessment Program funded both the IVAN trial (ref: 07/36/01) and this
   long-term follow-up of IVAN participants (ref: 07/36/501). The views and
   opinions expressed are those of the authors and do not necessarily
   reflect those of the NIHR Health Technology Assessment program, the
   NIHR, the UK National Health Service, or the Department of Health.
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NR 14
TC 11
Z9 11
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD SEP
PY 2020
VL 127
IS 9
BP 1191
EP 1200
DI 10.1016/j.ophtha.2020.03.020
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OH6OK
UT WOS:000582712500024
PM 32359843
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Messerschmidt, L
   Fischer, S
   Wiedemann, P
   Bringmann, A
   Hollborn, M
AF Messerschmidt, Luise
   Fischer, Sarah
   Wiedemann, Peter
   Bringmann, Andreas
   Hollborn, Margrit
TI Osmotic induction of cyclooxygenase-2 in RPE cells: Stimulation of
   inflammasome activation
SO MOLECULAR VISION
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; AGE-RELATED MACULOPATHY; BLOOD-PRESSURE;
   TRIAMCINOLONE ACETONIDE; MACULAR DEGENERATION; GENE-EXPRESSION;
   GROWTH-FACTORS; SODIUM; VEGF; COX-2
AB Purpose: Systemic hypertension is a risk factor of age-related macular degeneration, a disease associated with chronic retinal inflammation. The main cause of acute hypertension in the elderly is consumption of dietary salt (NaCl) resulting in increased extracellular osmolarity. The aim of the present study was to determine whether extracellular osmolarity regulates the expression of cyclooxygenase (COX) genes in cultured human retinal pigment epithelial (RPE) cells, and whether COX activity is involved in mediating the osmotic expression of key inflammatory (NLRP3 and IL1B) and angiogenic factor (VEGFA) genes.
   Methods: Extracellular hyperosmolarity was induced by addition of NaCl or sucrose. Gene expression was determined with real-time reverse transcription (RT)-PCR. Cytosolic interleukin-1 beta (IL-1 beta) and extracellular vascular endothelial growth factor (VEGF) levels were evaluated with enzyme-linked immunosorbent assay (ELISA).
   Results: Extracellular hyperosmolarity induced a dose-dependent increase in COX2 gene expression when > 10 mM NaCl was added to the culture medium, while COX1 gene expression was increased at higher doses (> 50 mM of added NaCl). Extracellular hypo-osmolarity decreased COX2 gene expression. High extracellular osmolarity also induced increases in the COX2 protein level. NaCl-induced expression of COX2 was mediated by various intracellular signal transduction molecules (p38 mitogen-activated protein kinase [p38 MAPK], extracellular signal-regulated kinases 1 and 2 [ERK1/2], and phosphatidylinositol-3 kinase [PI3K]), intracellular calcium signaling involving activation of phospholipase C gamma (PLC gamma) and protein kinase C alpha/beta (PKC alpha/beta), and the activity of nuclear factor of activated T cell 5 (NFAT5). Inhibition of fibroblast growth factor (FGF), transforming growth factor-beta (TGF-beta), and interleukin-1 (IL-1) receptor activities decreased NaCl-induced COX2 gene expression. Selective inhibition of COX2 activity decreased osmotic expression of the VEGFA, IL1B, and NLRP3 genes, and blocked the NaCl-induced increase in the cytosolic IL-1 beta level.
   Conclusions: The expression of COX2 in RPE cells is osmoresponsive, and depends on NFAT5. COX2 activity stimulates hyperosmotic expression of angiogenic (VEGFA) and inflammatory factor (IL1B and NLRP3) genes, and activation of the NLRP3 inflammasome in RPE cells.
C1 Univ Leipzig, Dept Ophthalmol, Leipzig, Germany.
   Univ Leipzig, Eye Hosp, Leipzig, Germany.
C3 Leipzig University; Leipzig University
RP Hollborn, M (通讯作者)，Univ Leipzig, Dept Ophthalmol, Fac Med, Liebigstr 10-14, D-04103 Leipzig, Germany.; Hollborn, M (通讯作者)，Univ Leipzig, Eye Hosp, Fac Med, Liebigstr 10-14, D-04103 Leipzig, Germany.
EM hollbm@medizin.uni-leipzig.de
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NR 52
TC 7
Z9 7
U1 1
U2 2
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUN 30
PY 2019
VL 25
BP 329
EP 344
PG 16
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA IH6RX
UT WOS:000474627500001
PM 31341381
DA 2022-11-30
ER

PT J
AU Staurenghi, G
   Lai, TYY
   Mitchell, P
   Wolf, S
   Wenzel, A
   Li, J
   Bhaumik, A
   Hykin, PG
AF Staurenghi, Giovanni
   Lai, Timothy Y. Y.
   Mitchell, Paul
   Wolf, Sebastian
   Wenzel, Andreas
   Li, Jun
   Bhaumik, Amitabha
   Hykin, Philip G.
CA PROMETHEUS Study Grp
TI Efficacy and Safety of Ranibizumab 0.5 mg for the Treatment of Macular
   Edema Resulting from Uncommon Causes
SO OPHTHALMOLOGY
LA English
DT Article
ID CENTRAL SEROUS CHORIORETINOPATHY; ENDOTHELIAL GROWTH-FACTOR;
   NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RETINAL VEIN OCCLUSION;
   INTRAVITREAL BEVACIZUMAB; COATS-DISEASE; STABILIZATION CRITERIA; LASER
   PHOTOCOAGULATION; PHOTODYNAMIC THERAPY; RESTORE-EXTENSION
AB Purpose: To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult patients with macular edema (ME) resulting from any cause other than diabetes, retinal vein occlusion, or neovascular age-related macular degeneration.
   Design: A phase 3, 12-month, double-masked, randomized, sham-controlled, multicenter study.
   Participants: One hundred seventy-eight eligible patients aged >= 18 years.
   Methods: Patients were randomized 2: 1 to receive either ranibizumab 0.5 mg (n = 118) or sham (n = 60) at baseline and month 1. From month 2, patients in both arms received open-label individualized ranibizumab treatment based on disease activity. A preplanned subgroup analysis was conducted on the primary end point on 5 predefined baseline ME etiologies (inflammatory/post-uveitis, pseudophakic or aphakic, central serous chorioretinopathy, idiopathic, and miscellaneous). Main Outcome Measures: Changes in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) from baseline to month 2 (primary end point) and month 12 and safety over 12 months.
   Results: Overall, 156 patients (87.6%) completed the study. The baseline characteristics were well balanced between the treatment arms. Overall, ranibizumab showed superior efficacy versus sham from baseline to month 2 (least squares mean BCVA, +5.7 letters vs. +2.9 letters; 1-sided P = 0.0111), that is, a treatment effect (TE) of +2.8 letters. The mean BCVA gain from baseline to month 12 was 9.6 letters with ranibizumab. The TE at month 2 was variable in the 5 predefined etiology subgroups, ranging from > 5-letter gain to 0.5-letter loss. The safety findings were consistent with the well-established safety profile of ranibizumab.
   Conclusions: The primary end point was met and ranibizumab showed superiority in BCVA gain over sham in treating ME due to uncommon causes, with a TE of +2.8 letters versus sham at month 2. At month 12, the mean BCVA gain was high (9.6 letters) in the ranibizumab arm; however, the TE was observed to be variable across the different etiology subgroups, reaching a > 1-line TE in BCVA in patients with ME resulting from inflammatory conditions/post-uveitis or after cataract surgery. Overall, ranibizumab was well tolerated with no new safety findings up to month 12. (C) 2018 by the American Academy of Ophthalmology.
C1 [Staurenghi, Giovanni] Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, I-20157 Milan, Italy.
   [Lai, Timothy Y. Y.] Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China.
   [Mitchell, Paul] Univ Sydney, Dept Ophthalmol, Sydney, NSW, Australia.
   [Mitchell, Paul] Univ Sydney, Westmead Inst Med Res, Sydney, NSW, Australia.
   [Wolf, Sebastian] Univ Bern, Bern Univ Hosp, Inselspital, Dept Ophthalmol, Bern, Switzerland.
   [Wenzel, Andreas; Li, Jun] Novartis Pharma AG, Basel, Switzerland.
   [Bhaumik, Amitabha] Novartis Pharmaceut, E Hanover, NJ USA.
   [Hykin, Philip G.] Moorfields Eye Hosp, London, England.
C3 University of Milan; Luigi Sacco Hospital; Chinese University of Hong
   Kong; University of Sydney; University of Sydney; Westmead Institute for
   Medical Research; University of Bern; University Hospital of Bern;
   Novartis; Novartis; University of London; University College London;
   Moorfields Eye Hospital NHS Foundation Trust
RP Staurenghi, G (通讯作者)，Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, I-20157 Milan, Italy.
EM giovanni.staurenghi@unimi.it
RI Wolf, Sebastian/B-8782-2008; Lai, Timothy Y Y/AAC-2120-2020; Staurenghi,
   Giovanni/K-4388-2017
OI Wolf, Sebastian/0000-0002-7467-7028; Lai, Timothy Y
   Y/0000-0002-7832-6428; Staurenghi, Giovanni/0000-0002-2299-5251
FU Bayer HealthCare (Leverkusen, Germany); Centervue (Padova, Italy);
   Heidelberg Engineering (Heidelberg Engineering); Novartis (Basel,
   Switzerland); Novartis Pharmaceuticals (East Hanover, NJ); Bayer
   (Leverkusen, Germany); Abbott (Lake Bluff, IL); Allergan (Dublin,
   Ireland); Roche (Basel, Switzerland); Genentech (South San Francisco,
   CA); Alcon (Fort Worth, TX); Novartis Pharma AG, Basel, Switzerland;
   National Institute for Health Research Biomedical Centre for Research in
   Ophthalmology
FX The author(s) have made the following disclosure(s): G.S.: Consultant -
   Novartis (Basel, Switzerland), Bayer HealthCare (Leverkusen, Germany),
   Allergan (Dublin, Ireland), Genentech (South San Francisco, CA), Roche
   (Basel, Switzerland), Heidelberg Engineering (Heidelberg, Germany), and
   Alcon (Fort Worth, TX); Financial support - Bayer HealthCare
   (Leverkusen, Germany), Centervue (Padova, Italy), Heidelberg Engineering
   (Heidelberg Engineering), and Novartis (Basel, Switzerland); Lecturer -
   Zeiss (Oberkochen, Germany); Patent - Ocular Instruments, Inc.
   (Bellevue, WA).; T.Y.Y.L.: Consultant - Allergan (Dublin, Ireland),
   Bayer Healthcare (Leverkusen, Germany), Novartis Pharmaceuticals (East
   Hanover, NJ), and Genentech (South San Francisco, CA); Financial support
   - Bayer Healthcare (Leverkusen, Germany) and Novartis Pharmaceuticals
   (East Hanover, NJ); Lecturer - Allergan (Dublin, Ireland), Bausch & Lomb
   (Bridgewater, NJ), Bayer Healthcare (Leverkusen, Germany), and Novartis
   Pharmaceuticals (East Hanover, NJ); P.M.: Consultant - Novartis (Basel,
   Switzerland), Bayer (Leverkusen, Germany), Abbott (Lake Bluff, IL),
   Allergan (Dublin, Ireland), Roche (Basel, Switzerland), Genentech (South
   San Francisco, CA); Financial support - Novartis (Basel, Switzerland),
   Bayer (Leverkusen, Germany), Abbott (Lake Bluff, IL), Allergan (Dublin,
   Ireland), Roche (Basel, Switzerland), Genentech (South San Francisco,
   CA); S.W.: Consultant - Alcon (Fort Worth, TX), Allergan (Dublin,
   Ireland), Bayer HealthCare (Leverkusen, Germany), Heidelberg Engineering
   (Heidelberg, Germany), Novartis (Basel, Switzerland), Optos
   (Dunfermline, Scotland), Roche (Basel, Switzerland), Zeiss (Oberkochen,
   Germany); Financial support - Bayer HealthCare (Leverkusen, Germany),
   Roche (Basel, Switzerland), Allergan (Dublin, Ireland), Alcon (Fort
   Worth, TX); P.G.H.: Consultant - Bayer HealthCare (Leverkusen, Germany),
   Novartis (Basel, Switzerland), Allergan (Dublin, Ireland); Financial
   support - Bayer HealthCare (Leverkusen, Germany), Allergan (Dublin,
   Ireland), and Novartis (Basel, Switzerland); Lecturer - Allergan
   (Dublin, Ireland) and Novartis (Basel, Switzerland); Supported and
   managed by Novartis Pharma AG, Basel, Switzerland; and supported by the
   National Institute for Health Research Biomedical Centre for Research in
   Ophthalmology (P.G.H.).
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NR 49
TC 17
Z9 18
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUN
PY 2018
VL 125
IS 6
BP 850
EP 862
DI 10.1016/j.ophtha.2017.12.002
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GG0MB
UT WOS:000432371600020
PM 29371007
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Dell'Omo, R
   Cassetta, M
   Dell'Omo, E
   di Salvatore, A
   Hughes, JM
   Aceto, F
   Porcellini, A
   Costagliola, C
AF Dell'Omo, Roberto
   Cassetta, Marilluccia
   Dell'Omo, Ermanno
   di Salvatore, Angela
   Hughes, John M.
   Aceto, Fabiana
   Porcellini, Antonio
   Costagliola, Ciro
TI Aqueous Humor Levels of Vascular Endothelial Growth Factor Before and
   After Intravitreal Bevacizumab in Type 3 Versus Type 1 and 2
   Neovascularization. A Prospective, Case-Control Study
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RETINAL ANGIOMATOUS PROLIFERATION; VERTEPORFIN PHOTODYNAMIC THERAPY;
   INDOCYANINE GREEN ANGIOGRAPHY; EPITHELIUM-DERIVED FACTOR; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; DIABETIC-RETINOPATHY;
   VITREOUS LEVELS; CHORIORETINAL ANASTOMOSIS; AVASTIN TREATMENT
AB PURPOSE: To determine the aqueous levels of vascular endothelial growth factor (VEGF) in patients with type 3 neovascularization (NV) secondary to age-related macular degeneration (AMD) and to compare the levels of those with type 1 and 2 NV secondary to AMD before and after administration of intravitreal bevacizumab (IVB).
   DESIGN: Prospective, case-control study.
   METHODS: Aqueous samples were collected from 29 eyes of 29 patients with untreated wet AMD at baseline (day of the first IVB), month 1 (day of the second IVB), and month 2 (day of the third IVB). Among them, 10 eyes presented with type 1, 9 with type 2, and 10 with type 3 NV. A group of 14 aqueous samples from 14 patients who underwent cataract surgery without other ocular or systemic disease comprised the controls. Main outcome measures were concentration of VEGF at baseline and after IVB in the 3 NV groups; secondary outcome measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes after IVB. Levels of VEGF were determined by commercially available enzyme-linked immunosorbent assay kits.
   RESULTS: VEGF concentrations in aqueous humor at baseline were higher in patients with type 3 NV when compared to controls (P = .0001) and type 1 and 2 NV patients (P = .002 and P = .0001 respectively). At month 1, levels of VEGF were significantly reduced compared to baseline (P < .05) and significantly lower compared to the controls (P < .005) in each NV group. These low levels were maintained at the 2-month interval. BCVA significantly improved in type 1 and 2 NV groups (P < .05). CMT significantly reduced in each NV group compared to baseline (P < .05).
   CONCLUSION: In eyes with untreated wet AMD, aqueous levels of VEGF are significantly higher in type 3 NV than in type 1 or 2 NV. Regardless of the type of NV, aqueous VEGF levels significantly reduce 1 month after IVB as compared to both the baseline measurements and the values recorded in age-matched controls. These decreases are maintained at 2 months after administering a second IVB 30 days after the initial injection. (Am J Ophthalmol 2012;153:155-161. (C) 2012 by Elsevier Inc. All rights reserved.)
C1 [Dell'Omo, Roberto; Aceto, Fabiana; Porcellini, Antonio; Costagliola, Ciro] Univ Molise, Dept Hlth Sci, Med Retina Unit, I-86100 Campobasso, Italy.
   [Dell'Omo, Roberto; Cassetta, Marilluccia; Dell'Omo, Ermanno; di Salvatore, Angela; Costagliola, Ciro] Casa Cura Villa Maria, Campobasso, Italy.
   [Hughes, John M.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
C3 University of Molise; University of Amsterdam; Academic Medical Center
   Amsterdam
RP Dell'Omo, R (通讯作者)，Univ Molise, Dept Hlth Sci, Med Retina Unit, Via F De Sanctis, I-86100 Campobasso, Italy.
EM robdellomo@libero.it
RI Porcellini, Antonio/AAC-6097-2019; Porcellini, Antonio/E-1900-2011;
   Cassetta, M./I-2496-2019; dell'Omo, Roberto/K-7328-2016; Costagliola,
   Ciro/G-5707-2012
OI Porcellini, Antonio/0000-0001-6882-9518; Cassetta,
   M./0000-0003-2633-5514; dell'Omo, Roberto/0000-0002-7663-8874;
   Costagliola, Ciro/0000-0001-8477-6188
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NR 45
TC 33
Z9 33
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JAN
PY 2012
VL 153
IS 1
BP 155
EP 161
DI 10.1016/j.ajo.2011.06.001
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 865LP
UT WOS:000298312700021
PM 21861975
DA 2022-11-30
ER

PT J
AU Zhu, Q
   Ziemssen, F
   Henke-Fahle, S
   Tatar, O
   Szurman, P
   Aisenbrey, S
   Schneiderhan-Marra, N
   Xu, X
   Grisanti, S
AF Zhu, Qi
   Ziemssen, Focke
   Henke-Fahle, Sigrid
   Tatar, Okay
   Szurman, Peter
   Aisenbrey, Sabine
   Schneiderhan-Marra, Nicole
   Xu, Xun
   Grisanti, Salvatore
CA Tuebingen Bevacizumab Study Grp
TI Vitreous levels of bevackumab and vascular endothelial growth factor-A
   in patients with choroidal neovascularization
SO OPHTHALMOLOGY
LA English
DT Article
ID EPITHELIUM-DERIVED FACTOR; MACULAR DEGENERATION; INTRAVITREAL
   BEVACIZUMAB; RANIBIZUMAB; AVASTIN; INJECTION; PHARMACOKINETICS;
   ANGIOGENESIS; PENETRATION; THERAPY
AB Purpose: To investigate the vitreous levels of bevacizumab and vascular endothelial growth factor-A (VEGF-A) after intravitreal injection of the drug in patients with choroidal neovascularization (CNV).
   Design: Interventional case series.
   Participants: Eleven eyes of 11 patients with submacular hemorrhage and CNV due to age-related macular degeneration (n = 10) or angioid streaks (n = 1).
   Methods: All patients were treatment naive except for a single dose of intravitreal injection of bevacizumab (1.25 mg/50 mu L dose) and subsequent vitrectomy after various intervals (1-101 days) because of active and progressive lesion. Intravitreal free bevacizumab and VEGF-A levels were measured using enzyme-linked immunosorbent assay and microsphere-based immunoassay, respectively. Vitreous VEGF-A isoforms were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting.
   Main Outcome Measures: Intravitreal bevacizumab and VEGF-A levels were measured and pharmacokinetic parameters were calculated.
   Results: Pharmacokinetics of intravitreal bevacizumab followed a 2-compartment model with initial and terminal half-lives of 0.5 and 6.7 days, respectively. Bevacizumab could be detected in all cases, ranging from 2.63 ng/ml to 165 mu g/ml. The peak concentration was observed on the second day after intravitreal bevacizumab injection. Vitreous free VEGF-A levels ranged from 0.2 to 33.9 pg/ml and showed a negative correlation with the bevacizumab concentration (P<0.001; r = -0.955) and a positive correlation with time (P<0.001; r = 0.964). However, the percentage expression of VEGF-A(165) exhibited a positive correlation with the bevacizumab concentration (P = 0.032, r = 0.645) and a negative correlation with time (P = 0.007, r = -0.755). A time-dependent increase was found for the percentage expression of VEGF-A(189) (P = 0.023, r = 0.673). Neither bevacizumab- nor time-related alterations were found for VEGF-A(121).
   Conclusions: Based on pharmacokinetics, the interval of 6-7 weeks would be appropriate for efficacy, although clinical trials should guide dosing recommendations. Vitreous levels of free VEGF-A showed a negative correlation with the bevacizumab concentration, which confirmed the in vivo binding affinity of bevacizumab to VEGF-A. The analysis of the VEGF-A isoforms suggests differences of interaction between bevacizumab and individual VEGF-A isoforms.
C1 [Grisanti, Salvatore] Univ Lubeck, Univ Eye Hosp, D-23538 Lubeck, Germany.
   [Zhu, Qi; Ziemssen, Focke; Henke-Fahle, Sigrid; Tatar, Okay; Szurman, Peter; Aisenbrey, Sabine; Grisanti, Salvatore; Tuebingen Bevacizumab Study Grp] Univ Tubingen, Univ Eye Hosp, Ctr Ophthalmol, D-72074 Tubingen, Germany.
   [Zhu, Qi; Schneiderhan-Marra, Nicole] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Dept Ophthalmol, Shanghai, Peoples R China.
   [Xu, Xun] Univ Tubingen, NMI, Nat & Med Sci Inst, Reutlingen, Germany.
C3 University of Lubeck; Eberhard Karls University of Tubingen; Eberhard
   Karls University Hospital; Shanghai Jiao Tong University; Eberhard Karls
   University of Tubingen
RP Grisanti, S (通讯作者)，Univ Lubeck, Univ Eye Hosp, Ratzeburger Allee, D-23538 Lubeck, Germany.
EM Salvatore.Grisanti@uk-sh.de
RI , Ziemssen/B-9564-2009; Ziemssen, Focke/AAY-1686-2021
OI , Ziemssen/0000-0002-3873-0581; 
FU Jung-Stiftung fur Wissenschaft and Forschung, Germany
FX The authors have no commercial or proprietary interest in the products
   or companies mentioned in the article.; Supported by a grant from
   Jung-Stiftung fur Wissenschaft and Forschung, Germany.; Drs. Zhu,
   Ziemssen, and Xu contributed equally to this work.
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NR 23
TC 133
Z9 140
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD OCT
PY 2008
VL 115
IS 10
BP 1750
EP 1755
DI 10.1016/j.ophtha.2008.04.023
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 357NJ
UT WOS:000259852200016
PM 18708261
DA 2022-11-30
ER

PT J
AU Tan, CS
   Hariprasad, SM
   Lim, LW
AF Tan, Colin S.
   Hariprasad, Seenu M.
   Lim, Louis W.
TI New Paradigms in Polypoidal Choroidal Vasculopathy Management: The
   Impact of Recent Multicenter, Randomized Clinical Trials
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID VERTEPORFIN PHOTODYNAMIC THERAPY; MASSIVE SUBMACULAR HEMORRHAGE;
   ONE-YEAR OUTCOMES; JAPANESE PATIENTS; MACULAR DEGENERATION; RANIBIZUMAB;
   COMBINATION; EFFICACY; AFLIBERCEPT; EVEREST
C1 [Tan, Colin S.; Lim, Louis W.] Tan Tock Seng Hosp, Natl Healthcare Grp Eye Inst, 11 Jalan Tan Tock Seng, Singapore, Singapore.
   [Hariprasad, Seenu M.] Univ Chicago, Dept Ophthalmol & Visual Sci, 5841 S Maryland Ave,MC2114, Chicago, IL 60637 USA.
C3 Tan Tock Seng Hospital; University of Chicago
RP Tan, CS (通讯作者)，Tan Tock Seng Hosp, Natl Healthcare Grp Eye Inst, 11 Jalan Tan Tock Seng, Singapore, Singapore.
EM Colintan_eye@yahoo.com.sg; retina@uchicago.edu; limwy1987@gmail.com
RI Tan, Colin S/K-8972-2012
OI Tan, Colin S/0000-0003-3088-5690
FU National Medical Research Council, Singapore
FX Dr. Tan received a grant from the National Medical Research Council,
   Singapore, and has received honoraria and conference support from Bayer
   and Novartis outside the submitted work. Dr. Hariprasad is a consultant
   or on the speakers bureau for Alcon, Allergan, Bayer, OD-OS, Clearside
   Biomedical, Ocular Therapeutix, Alimera Sciences, Leica, Spark, and
   Regeneron. Dr. Lim reports no relevant financial disclosures.
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NR 20
TC 6
Z9 6
U1 0
U2 1
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD JAN
PY 2018
VL 49
IS 1
BP 4
EP 10
DI 10.3928/23258160-20171215-01
PG 7
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA FS7PP
UT WOS:000419990200001
PM 29304260
DA 2022-11-30
ER

PT J
AU Maa, AY
   Medert, CM
   Lu, XQ
   Janjua, R
   Howell, AV
   Hunt, KJ
   McCord, S
   Giangiacomo, A
   Lynch, MG
AF Maa, April Y.
   Medert, Charles M.
   Lu, Xiaoqin
   Janjua, Rabeea
   Howell, Ashley, V
   Hunt, Kelly J.
   McCord, Sarah
   Giangiacomo, Annette
   Lynch, Mary G.
TI Diagnostic Accuracy of Technology-based Eye Care Services The
   Technology-based Eye Care Services Compare Trial Part I
SO OPHTHALMOLOGY
LA English
DT Article
ID DIABETIC-RETINOPATHY; OPTIC DISC; SCREENING-PROGRAM; TELEOPHTHALMOLOGY;
   AGREEMENT; OPHTHALMOLOGISTS; IMAGES
AB Purpose: Ophthalmologic telemedicine has the ability to provide eye care for patients remotely, and many countries have used screening tele-ophthalmology programs for several years. One such initiative at the Veterans Affairs (VA) Healthcare System is Technology-based Eye Care Services (TECS). The TECS services are located in primary care clinics and provide basic screening eye care, including vision, refraction, and retinal photography. Eye care providers ("readers") review the clinical data and recommend appropriate follow-up. One of the most common referrals from TECS has been for glaucoma, and this study was powered for glaucoma/glaucoma suspect detection. The current study was undertaken to identify aspects of the protocol that could be refined to enhance accuracy.
   Design: Prospective comparison between the standard TECS protocol versus a face-to-face (FTF) examination on 256 patients, all of whom had no known history of significant ocular disease.
   Participants: Patients with no known ocular disease who were scheduled for an in-person eye appointment at the Atlanta VA. Patients underwent screening through the TECS protocol and received an FTF examination on the same day (gold standard). The TECS readers were masked to the results of the FTF examination.
   Main Outcome Measures: Percent agreement, kappa, sensitivity, and specificity were calculated for the TECS readers' interpretations versus the FTF examination.
   Results: The TECS readers showed substantial agreement for cataract (kappa >= 0.71) and diabetic retinopathy (kappa >= 0.61) and moderate to substantial agreement for glaucoma/glaucoma suspect (kappa >= 0.52) compared with an FTF examination. Age-related macular degeneration (AMD) showed moderate agreement (kappa >= 0.34). Percent agreement with the TECS protocol was high (84.3%-98.4%) for each of the disease categories. Overall sensitivity and specificity were >= 75% and >= 55%, respectively, for any diagnosis resulting in referral. Inter-reader and intra-reader agreement was substantial for most diagnoses (kappa > 0.61) with percent agreements ranging from 66% to 99%.
   Conclusions: Our results indicate that the standard TECS protocol is accurate when compared with an FTF examination for the detection of common eye diseases. The inclusion of additional testing such as OCT could further enhance diagnostic capability. Published by Elsevier on behalf of the American Academy of Ophthalmology
C1 [Maa, April Y.; Lu, Xiaoqin; Janjua, Rabeea; Giangiacomo, Annette] Atlanta Vet Affairs Hlth Care Syst, TECS Div, Reg Telehlth Serv, Atlanta, GA USA.
   [Maa, April Y.; Lu, Xiaoqin; Lynch, Mary G.] Emory Univ, Sch Med, Atlanta, GA USA.
   [Medert, Charles M.] Univ Miami, Bascom Palmer Eye Inst, Miami, FL USA.
   [Howell, Ashley, V; Hunt, Kelly J.] Ralph A Johnson Dept Vet Affairs, Charleston Hlth Equ & Rural Outreach Innovat Ctr, Med Ctr, Charleston, SC USA.
   [McCord, Sarah] New York Eye & Ear Infirm, New York, NY 10003 USA.
   [Lynch, Mary G.] Atlanta Vet Affairs Hlth Care Syst, Ophthalmol Div, Surg Serv, Atlanta, GA USA.
C3 Emory University; Bascom Palmer Eye Institute; University of Miami; New
   York Eye & Ear Infirmary of Mount Sinai
RP Maa, AY (通讯作者)，1670 Clairmont Rd MC 112E, Decatur, GA 30033 USA.
EM amaa@emory.edu
FU Atlanta Clinical and Translational Institute Translational Research
   grant
FX Partially funded by an Atlanta Clinical and Translational Institute
   Translational Research grant. The funding source had no role in the
   design or conduct of this study.
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NR 26
TC 24
Z9 24
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JAN
PY 2020
VL 127
IS 1
BP 38
EP 44
DI 10.1016/j.ophtha.2019.07.026
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JW7JM
UT WOS:000503224300016
PM 31522900
DA 2022-11-30
ER

PT J
AU Rim, TH
   Yoo, TK
   Kwak, J
   Lee, JS
   Kim, SH
   Kim, DW
   Kim, SS
AF Rim, Tyler Hyungtaek
   Yoo, Tae Keun
   Kwak, Jiyong
   Lee, Jihei Sara
   Kim, Seo Hee
   Kim, Dong Wook
   Kim, Sung Soo
TI Long-Term Regular Use of Low-Dose Aspirin and Neovascular Age-Related
   Meacular Degeneration National Sample Cohort 2010-2015
SO OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; RISK-FACTORS; RANDOMIZED-TRIAL; ASSOCIATION;
   MACULOPATHY; STROKE; OCCLUSION
AB Purpose: The association between long-term cardioprotective aspirin use and neovascular age-related macular degeneration (AMD) is controversial. This study was undertaken to estimate the risk of neovascular AMD with long-term regular use of low-dose aspirin.
   Design: Retrospective population-based study, using a nationwide cohort from a variety of clinics and hospitals in South Korea.
   Participants: Nonregular aspirin users and regular aspirin users under national health insurance, aged >= 45 years, who were followed from 2010 to 2015, were identified.
   Methods: Incidence per 10 000 person-years for neovascular AMD was estimated. Long-term regular use of low-dose aspirin was defined as sustained intake of >= 100 mg aspirin with >= 1044 days prescription between 2005 and 2009. Nonregular aspirin users included occasional users or nonusers. The analyses included a propensity score-adjusted analysis in a large, randomly selected, unmatched whole cohort (n = 482 613); propensity score-matched analysis in a matched cohort (n = 74 196); and maximally adjusted analysis in the unmatched whole cohort (n = 482 613).
   Main Outcome Measures: Incidence of newly developed neovascular AMD using the registration code for intractable disease under national health insurance.
   Results: Incidence of neovascular AMD was 3.5 among nonregular aspirin users and 7.2 among regular aspirin users per 10 000 person-years in the unmatched whole cohort. However, propensity scoreeadjusted analyses revealed no association between aspirin use and neovascular AMD (adjusted hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.73-1.30). Likewise, propensity scoreematched analyses showed no association; incidences of neovascular AMD were 7.5 and 7.1 among nonregular aspirin users and regular aspirin users (crude HR, 0.94; 95% CI, 0.70-1.28), respectively. A maximally adjusted model, including age, sex, income, residential area, and history of 100 randomly selected types of generic drugs, showed no association (adjusted HR, 0.95; 95% CI, 0.71-1.28).
   Conclusions: Wefound no association between long-term regular use of low-dose aspirin for 5 years and future incidence of neovascular AMD. Thus, this large-scale study suggests that regular, long-term use of low-dose aspirin appears to be safe with respect to the new development of neovascular AMD. (C) 2018 by the American Academy of Ophthalmology
C1 [Rim, Tyler Hyungtaek; Yoo, Tae Keun; Kwak, Jiyong; Lee, Jihei Sara; Kim, Seo Hee; Kim, Sung Soo] Yonsei Univ, Severance Hosp, Inst Vis Res, Dept Ophthalmol,Coll Med, 50 Yonsei Ro, Seoul 03722, South Korea.
   [Kim, Dong Wook] Natl Hlth Insurance Serv, Dept Policy Res Affairs, Ilsan Hosp, Goyang, Gyeonggi Do, South Korea.
C3 Yonsei University; Yonsei University Health System; National Health
   Insurance Service; NHIS Ilsan Hospital
RP Kim, SS (通讯作者)，Yonsei Univ, Severance Hosp, Inst Vis Res, Dept Ophthalmol,Coll Med, 50 Yonsei Ro, Seoul 03722, South Korea.
EM semekim@yuhs.ac
RI Yoo, Tae Keun/Q-3620-2019
OI Yoo, Tae Keun/0000-0003-0890-8614; Rim, Tyler
   Hyungtaek/0000-0001-6465-2620; Lee, Jihei Sara/0000-0002-1585-168X;
   Kwak, Jay Jiyong/0000-0002-7738-9136; Kim, Sung Soo/0000-0002-0574-7993
FU Yonsei University College of Medicine [6-2017-0089]
FX Supported by a faculty research grant from Yonsei University College of
   Medicine for 2017 (6-2017-0089). The sponsor or funding organization had
   no role in the design or conduct of this research.
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NR 23
TC 15
Z9 15
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD FEB
PY 2019
VL 126
IS 2
BP 274
EP 282
DI 10.1016/j.ophtha.2018.09.014
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HI2YI
UT WOS:000456312400024
PM 30240791
DA 2022-11-30
ER

PT J
AU Ferluga, J
   Kouser, L
   Murugaiah, V
   Sim, RB
   Kishore, U
AF Ferluga, Janez
   Kouser, Lubna
   Murugaiah, Valarmathy
   Sim, Robert B.
   Kishore, Uday
TI Potential influences of complement factor H in autoimmune inflammatory
   and thrombotic disorders
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Autoimmunity; Age-related macular degeneration; Factor H;
   Self-tolerance; Thrombotic disorder
ID HEMOLYTIC-UREMIC SYNDROME; INTEGRIN-ASSOCIATED PROTEIN;
   SYSTEMIC-LUPUS-ERYTHEMATOSUS; T-CELL-ACTIVATION; REGULATORY DENDRITIC
   CELLS; B-LYMPHOCYTE ACTIVATION; INNATE IMMUNE-RESPONSE; DENSE DEPOSIT
   DISEASE; VON-WILLEBRAND-FACTOR; AMINO-ACID-SEQUENCE
AB Complement system homeostasis is important for host self-protection and anti-microbial immune surveillance, and recent research indicates roles in tissue development and remodelling. Complement also appears to have several points of interaction with the blood coagulation system. Deficiency and altered function due to gene mutations and polymorphisms in complement effectors and regulators, including Factor H, have been associated with familial and sporadic autoimmune inflammatory thrombotic disorders, in which autoantibodies play a part. These include systemic lupus erythematosus, rheumatoid arthritis, atypical haemolytic uremic syndrome, anti-phospholipid syndrome and age-related macular degeneration. Such diseases are generally complex multigenic and heterogeneous in their symptoms and predisposition/susceptibility. They usually need to be triggered by vascular trauma, drugs or infection and non-complement genetic factors also play a part. Underlying events seem to include decline in peripheral regulatory T cells, dendritic cell, and B cell tolerance, associated with alterations in lymphoid organ microenvironment. Factor H is an abundant protein, synthesised in many cell types, and its reported binding to many different ligands, even if not of high affinity, may influence a large number of molecular interactions, together with the accepted role of Factor H within the complement system. Factor H is involved in mesenchymal stem cell mediated tolerance and also contributes toself-tolerance by augmenting iC3b production and opsonisation of apoptotic cells for their silent dendritic cell engulfment via complement receptor CR3, which mediates anti-inflammatory-tolerogenic effects in the apoptotic cell context. There may be co-operation with other phagocytic receptors, such as complement Cl q receptors, and the Tim glycoprotein family, which specifically bind phosphatidylserine expressed on the apoptotic cell surface. Factor H is able to discriminate between self and nonself surfaces for self-protection and anti-microbe defence. Factor H, particularly as an abundant platelet protein, may also modulate blood coagulation, having an anti-thrombotic role. Here, we review a number of interaction pathways in coagulation and in immunity, together with associated diseases, and indicate where Factor H may be expected to exert an influence, based on reports of the diversity of ligands for Factor H. (C) 2017 Elsevier Ltd. All rights reserved.
C1 [Ferluga, Janez; Kouser, Lubna; Murugaiah, Valarmathy; Kishore, Uday] Brunel Univ London, Coll Hlth & Life Sci, Biosci, Uxbridge UB8 3PH, Middx, England.
   [Sim, Robert B.] Univ Oxford, Dept Pharmacol, Mansfield Rd, Oxford OX1 3QT, England.
C3 Brunel University; University of Oxford
RP Kishore, U (通讯作者)，Brunel Univ London, Coll Hlth & Life Sci, Biosci, Uxbridge UB8 3PH, Middx, England.
EM ukishore@hotmail.com
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD APR
PY 2017
VL 84
SI SI
BP 84
EP 106
DI 10.1016/j.molimm.2017.01.015
PG 23
WC Biochemistry & Molecular Biology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Immunology
GA ET3TE
UT WOS:000400201600012
PM 28216098
DA 2022-11-30
ER

PT J
AU Fernando, N
   Natoli, R
   Valter, K
   Provis, J
   Rutar, M
AF Fernando, Nilisha
   Natoli, Riccardo
   Valter, Krisztina
   Provis, Jan
   Rutar, Matt
TI The broad-spectrum chemokine inhibitor NR58-3.14.3 modulates
   macrophage-mediated inflammation in the diseased retina
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; SENILE MACULAR DEGENERATION; MULLER
   CELLS; MICROGLIAL ACTIVATION; BONE-MARROW; GIANT-CELLS; MOUSE MODEL;
   EXPRESSION; PHOTORECEPTORS; RECRUITMENT
AB Background: The activity of macrophages is implicated in the progression of retinal pathologies such as atrophic age-related macular degeneration (AMD), where they accumulate among the photoreceptor layer and subretinal space. This process is aided by the local expression of chemokines, which furnish these cells with directional cues that augment their migration to areas of retinal injury. While these qualities make chemokines a potential therapeutic target in curtailing damaging retinal inflammation, their wide variety and signalling redundancy pose challenges in broadly modulating their activity. Here, we examine the efficacy of the broad-spectrum chemokine inhibitor NR58-3.14.3-a suppressor of Ccl- and Cxcl- chemokine pathways-in suppressing macrophage activity and photoreceptor death, using a light-induced model of outer retinal atrophy and inflammation.
   Methods: Photo-oxidative damage was induced in SD rats via exposure to 1000 lux of light for 24 h, after which animals were euthanized at 0- or 7-day post-exposure time points. Prior to damage, NR58-3.14.3 was injected intravitreally. Retinas were harvested and evaluated for the effect of NR58-3.14.3 on subretinal macrophage accumulation and cytokine expression profile, as well as photoreceptor degeneration.
   Results: We report that intravitreal administration of NR58-3.14.3 reduces the accumulation of macrophages in the outer retina following exposure to light damage, at both 0- and 7-day post-exposure time points. Injection of NR58-3.14.3 also reduced the up-regulation of inflammatory markers including of Il6, Ccl3, and Ccl4 in infiltrating macrophages, which are promoters of their pathogenic activity in the retina. Finally, NR58-3.14.3-injected retinas displayed markedly reduced photoreceptor death following light damage, at both 0 and 7 days post-exposure.
   Conclusions: Our findings indicate that NR58-3.14.3 is effective in inhibiting subretinal macrophage accumulation in light-induced retinal degeneration and illustrate the potential of broad-spectrum chemokine inhibitors as novel therapeutic agents in thwarting retinal inflammation. Although broad-spectrum chemokine inhibitors may not be appropriate for all retinal inflammatory conditions, our results suggest that they may be beneficial for retinal dystrophies in which chemokine expression and subretinal macrophage accumulation are implicated, such as advanced AMD.
C1 [Fernando, Nilisha; Natoli, Riccardo; Valter, Krisztina; Provis, Jan; Rutar, Matt] Australian Natl Univ, John Curtin Sch Med Res, Bldg 131,Garran Rd, Canberra, ACT 2601, Australia.
   [Natoli, Riccardo; Valter, Krisztina; Provis, Jan] Australian Natl Univ, ANU Med Sch, GPO Box 4, Canberra, ACT 2601, Australia.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University
RP Rutar, M (通讯作者)，Australian Natl Univ, John Curtin Sch Med Res, Bldg 131,Garran Rd, Canberra, ACT 2601, Australia.
EM matt.rutar@anu.edu.au
RI Valter, Krisztina/L-3015-2016
OI Natoli, Riccardo/0000-0002-9350-0439; Rutar,
   Matthew/0000-0002-8893-5120; Valter, Krisztina/0000-0002-2033-0408;
   Fernando, Nilisha/0000-0002-8488-1348
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NR 77
TC 20
Z9 22
U1 0
U2 7
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD FEB 24
PY 2016
VL 13
AR 47
DI 10.1186/s12974-016-0514-x
PG 14
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA DE6WT
UT WOS:000370776100001
PM 26911327
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wigg, JP
   Zhang, H
   Yang, D
AF Wigg, Jonathan P.
   Zhang, Hong
   Yang, Dong
TI A Quantitative and Standardized Method for the Evaluation of Choroidal
   Neovascularization Using MICRON III Fluorescein Angiograms in Rats
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; IN-VIVO;
   MONOCLONAL-ANTIBODY; MURINE MODEL; LASER; MICE; AGE; INHIBITOR;
   RETINOPATHY
AB Introduction
   In-vivo imaging of choroidal neovascularization (CNV) has been increasingly recognized as a valuable tool in the investigation of age-related macular degeneration (AMD) in both clinical and basic research applications. Arguably the most widely utilised model replicating AMD is laser generated CNV by rupture of Bruch's membrane in rodents. Heretofore CNV evaluation via in-vivo imaging techniques has been hamstrung by a lack of appropriate rodent fundus camera and a non-standardised analysis method. The aim of this study was to establish a simple, quantifiable method of fluorescein fundus angiogram (FFA) image analysis for CNV lesions.
   Methods
   Laser was applied to 32 Brown Norway Rats; FFA images were taken using a rodent specific fundus camera (Micron III, Phoenix Laboratories) over 3 weeks and compared to conventional ex-vivo CNV assessment. FFA images acquired with fluorescein administered by intraperitoneal injection and intravenous injection were compared and shown to greatly influence lesion properties. Utilising commonly used software packages, FFA images were assessed for CNV and chorioretinal burns lesion area by manually outlining the maximum border of each lesion and normalising against the optic nerve head. Net fluorescence above background and derived value of area corrected lesion intensity were calculated.
   Results
   CNV lesions of rats treated with anti-VEGF antibody were significantly smaller in normalised lesion area (p<0.001) and fluorescent intensity (p<0.001) than the PBS treated control two weeks post laser. The calculated area corrected lesion intensity was significantly smaller (p<0.001) in anti-VEGF treated animals at 2 and 3 weeks post laser. The results obtained using FFA correlated with, and were confirmed by conventional lesion area measurements from isolectin stained choroidal flatmounts, where lesions of anti-VEGF treated rats were significantly smaller at 2 weeks (p = 0.049) and 3 weeks (p<0.001) post laser.
   Conclusion
   The presented method of in-vivo FFA quantification of CNV, including acquisition variable corrections, using the Micron III system and common use software establishes a reliable method for detecting and quantifying CNV enabling longitudinal studies and represents an important alternative to conventional CNV quantification methods.
C1 [Wigg, Jonathan P.; Zhang, Hong; Yang, Dong] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, East Melbourne, Vic, Australia.
   [Zhang, Hong] Harbin Med Univ, Hosp Eye, Harbin, Heilongjiang Pr, Peoples R China.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; Harbin Medical University
RP Zhang, H (通讯作者)，Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, East Melbourne, Vic, Australia.
EM hong.zhang@unimelb.edu.au
RI Zhang, Hong/AAX-9632-2020
FU National Health and Medical Research Council (NHMRC) [APP1047603];
   National Natural Science Foundation of China (NNSFC) [81201184];
   Heilongjiang Provincial Nature Science Grants [LC2012C24]; Foundation
   for the New Century Talents by the Educational Committee of Heilongjiang
   Province [1251-NCET-011]; Doctoral Program of Higher Education Research
   Fund [20132307110027];  [2014CJHB006]
FX This work was supported by the following sources of funding: 1. National
   Health and Medical Research Council (NHMRC, http://www.nhmrc.gov.au/)
   Grant No APP1047603, HZ; 2. National Natural Science Foundation of China
   (NNSFC http://www.nsfc.gov.cn/) Grant No. 81201184, HZ; 3. Heilongjiang
   Provincial Nature Science Grants (http://www.nsf.hljkj.cn) Grant No.
   LC2012C24; 4. Foundation for the New Century Talents by the Educational
   Committee of Heilongjiang Province (http://www.hlje.net) Grant No.
   1251-NCET-011).; 5. Support Program for Changjiang Scholars candidate
   (http://www.hlje.net) Grant No. 2014CJHB006, HZ; and 6. Doctoral Program
   of Higher Education Research Fund (http://www.nsf.hljkj.cn) Grant No.
   20132307110027, HZ. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 41
TC 11
Z9 11
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 29
PY 2015
VL 10
IS 5
AR e0128418
DI 10.1371/journal.pone.0128418
PG 18
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CJ2MQ
UT WOS:000355319400090
PM 26024231
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Mandas, A
   Mereu, RM
   Catte, O
   Saba, A
   Serchisu, L
   Costaggiu, D
   Peiretti, E
   Caminiti, G
   Vinci, M
   Casu, M
   Piludu, S
   Fossarello, M
   Manconi, PE
   Dessi, S
AF Mandas, Antonella
   Mereu, Rosa Maria
   Catte, Olga
   Saba, Antonio
   Serchisu, Luca
   Costaggiu, Diego
   Peiretti, Enrico
   Caminiti, Giulia
   Vinci, Michela
   Casu, Maura
   Piludu, Stefania
   Fossarello, Maurizio
   Manconi, Paolo Emilio
   Dessi, Sandra
TI Cognitive impairment and age-related vision disorders: their possible
   relationship and the evaluation of the use of aspirin and statins in a
   65 years-and-over Sardinian population
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Article
DE age-related vision disorders; dementia; statins; aspirin; elderly
ID BRAIN CHOLESTEROL-SYNTHESIS; MINI-MENTAL-STATE; MACULAR DEGENERATION;
   ALZHEIMERS-DISEASE; RISK-FACTORS; DEMENTIA; ASSOCIATION; DECLINE;
   DRUSEN; CLASSIFICATION
AB Neurological disorders (Alzheimer's disease, vascular and mixed dementia) and visual loss (cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy) are among the most common conditions that afflict people of at least 65?years of age. An increasing body of evidence is emerging, which demonstrates that memory and vision impairment are closely, significantly, and positively linked and that statins and aspirin may lessen the risk of developing age-related visual and neurological problems. However, clinical studies have produced contradictory results. Thus, the intent of the present study was to reliably establish whether a relationship exist between various types of dementia and age-related vision disorders, and to establish whether statins and aspirin may or may not have beneficial effects on these two types of disorders. We found that participants with dementia and/or vision problems were more likely to be depressed and displayed worse functional ability in basic and instrumental activities of daily living than controls. Mini mental state examination scores were significantly lower in patients with vision disorders compared to subjects without vision disorders. A closer association with macular degeneration was found in subjects with Alzheimer's disease than in subjects without dementia or with vascular dementia, mixed dementia, or other types of age-related vision disorders. When we considered the associations between different types of dementia and vision disorders and the use of statins and aspirin, we found a significant positive association between Alzheimer's disease and statins on their own or in combination with aspirin, indicating that these two drugs do not appear to reduce the risk of Alzheimer's disease or improve its clinical evolution and may, on the contrary, favor its development. No significant association in statin use alone, aspirin use alone, or the combination of these was found in subjects without vision disorders but with dementia, and, similarly, none in subjects with vision disorders but without dementia. Overall, these results confirm the general impression so far; namely, that macular degeneration may contribute to cognitive disorders (Alzheimer's disease in particular). In addition, they also suggest that, while statin and aspirin use may undoubtedly have some protective effects, they do not appear to be magic pills against the development of cognitive impairment or vision disorders in the elderly.
C1 [Mandas, Antonella; Serchisu, Luca; Costaggiu, Diego; Manconi, Paolo Emilio; Dessi, Sandra] Univ Cagliari, Dipartimento Sci Med, I-09042 Cagliari, Italy.
   [Mereu, Rosa Maria; Catte, Olga; Saba, Antonio] Ctr Alzheimer & Disturbi Memoria, Div Geriatr, Cagliari, Italy.
   [Peiretti, Enrico; Caminiti, Giulia; Vinci, Michela; Casu, Maura; Piludu, Stefania; Fossarello, Maurizio] Univ Cagliari, Dipartimento Sci Chirurg & Odontoiatr, Clin Oculist, I-09042 Cagliari, Italy.
C3 University of Cagliari; University of Cagliari
RP Mandas, A (通讯作者)，Univ Cagliari, Dipartimento Sci Med, SS 554 Bivio Sestu, I-09042 Cagliari, Italy.
EM sdessi@unica.it
RI Fossarello, Maurizio/AAD-8235-2021; Fossarello, Maurizio/G-2032-2015
OI Peiretti, Enrico/0000-0003-1088-0163; Fossarello,
   Maurizio/0000-0003-1520-7760
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NR 48
TC 15
Z9 17
U1 0
U2 15
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD NOV 7
PY 2014
VL 6
AR 309
DI 10.3389/fnagi.2014.00309
PG 9
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AY9OE
UT WOS:000347879500001
PM 25426067
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Lee, WJA
   Shao, SC
   Liao, TC
   Lin, SJ
   Lai, CC
   Lai, ECC
AF Lee, Wan-Ju Annabelle
   Shao, Shih-Chieh
   Liao, Tzu-Chi
   Lin, Swu-Jane
   Lai, Chi-Chun
   Lai, Edward Chia-Cheng
TI Effect Modification by Indication to the Risks of Major Thromboembolic
   Adverse Events in Patients Receiving Intravitreal Anti-Vascular
   Endothelial Growth Factor Treatment: A Population-Based Retrospective
   Cohort Study
SO BIODRUGS
LA English
DT Article
ID INSURANCE RESEARCH DATABASE; ACUTE MYOCARDIAL-INFARCTION; MACULAR
   DEGENERATION; NATIONAL-HEALTH; SYSTEMIC SAFETY; RANIBIZUMAB;
   AFLIBERCEPT; STROKE; COMPLICATIONS; VALIDATION
AB Background The association between intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment and the risk of major thromboembolic adverse events (TAEs) remains under debate. This study aimed to examine associated risks of TAEs in patients receiving intravitreal anti-VEGF treatment, and effect modification by different indications. Methods This retrospective cohort study analyzed Taiwan's National Health Insurance Database during 2011-2017 to identify neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) patients newly receiving intravitreal aflibercept or ranibizumab. We followed up patients for 2 years, or until the occurrence of TAEs, including ischemic heart disease, ischemic stroke, transient ischemic attack, deep vein thrombosis, and pulmonary embolism, death, or the end of the study period (i.e., 31 December 2018). We compared the risk of TAEs between patients with aflibercept and ranibizumab using Cox-proportional hazard models. We examined statistical interactions between the anti-VEGF treatment (i.e., ranibizumab and aflibercept) and indications (i.e., nAMD and DME) with regard to the outcome of TAEs. Results We included 12,215 nAMD and 7532 DME patients. Among nAMD patients, those receiving aflibercept had lower risk of TAEs (adjusted hazard ratio [HR] 0.85; 95% CI 0.77-0.94) compared with those receiving ranibizumab. However, among DME patients, those receiving aflibercept had no differences in the risk of TAEs (1.14; 0.97-1.35) compared with those receiving ranibizumab. Among patients treated with ranibizumab, the DME group had a higher risk of TAEs than the nAMD group (HR 1.15; 95% CI 1.03-1.28); similar results were observed in patients treated with aflibercept (HR 1.53; 95% CI 1.27-1.85). When DME patients were treated with aflibercept, the risk of TAEs was 31% higher than when nAMD patients were treated with ranibizumab (HR 1.31; 95% CI 1.09-1.56; p < 0.05). The p-value for statistical interaction between the anti-VEGF treatment and indications was 0.0033. Conclusions Patients treated with aflibercept or ranibizumab for different indications may be associated with varying risk of TAEs. The findings provide evidence to support treatment selection, taking indications and TAE risk into consideration.
C1 [Lee, Wan-Ju Annabelle] Chi Mei Med Ctr, Dept Ophthalmol, Tainan, Taiwan.
   [Lee, Wan-Ju Annabelle; Shao, Shih-Chieh; Liao, Tzu-Chi; Lai, Edward Chia-Cheng] Natl Cheng Kung Univ, Coll Med, Sch Pharm, Inst Clin Pharm & Pharmaceut Sci, Tainan, Taiwan.
   [Lee, Wan-Ju Annabelle] Chung Hwa Univ Med Technol, Dept Optometry, Tainan, Taiwan.
   [Shao, Shih-Chieh] Keelung Chang Gung Mem Hosp, Dept Pharm, Keelung, Taiwan.
   [Lin, Swu-Jane] Univ Illinois, Coll Pharm, Dept Pharm Syst Outcomes & Policy, Chicago, IL USA.
   [Lai, Chi-Chun] Chang Gung Univ, Coll Med, Taoyuan, Taiwan.
   [Lai, Chi-Chun] Keelung Chang Gung Mem Hosp, Dept Ophthalmol, Keelung, Taiwan.
C3 Chi Mei Hospital; National Cheng Kung University; Chung Hua University;
   Chang Gung Memorial Hospital; University of Illinois System; University
   of Illinois Chicago; University of Illinois Chicago Hospital; Chang Gung
   University; Chang Gung Memorial Hospital
RP Lai, ECC (通讯作者)，Natl Cheng Kung Univ, Coll Med, Sch Pharm, Inst Clin Pharm & Pharmaceut Sci, Tainan, Taiwan.
EM edward_lai@mail.ncku.edu.tw
RI Lee, Wan-Ju/AAC-7025-2020
OI Lee, Wan-Ju/0000-0002-9972-8899; Lai, Chi-Chun/0000-0001-9547-7212
FU Ministry of Science and Technology of Taiwan [107-2320-B-006-070-MY3]
FX The Ministry of Science and Technology of Taiwan
   (107-2320-B-006-070-MY3). The funding source had no role in the design,
   analysis, interpretation, or reporting of results, or in the decision to
   submit the manuscript for publication.
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NR 38
TC 1
Z9 1
U1 3
U2 3
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 1173-8804
EI 1179-190X
J9 BIODRUGS
JI Biodrugs
PD MAR
PY 2022
VL 36
IS 2
BP 205
EP 216
DI 10.1007/s40259-022-00516-y
EA MAR 2022
PG 12
WC Oncology; Immunology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Immunology; Pharmacology & Pharmacy
GA 0H8MC
UT WOS:000762936300001
PM 35230656
DA 2022-11-30
ER

PT J
AU Rajagopalan, L
   Ghosn, C
   Tamhane, M
   Almazan, A
   Andrews-Jones, L
   Kulkarni, A
   Christie, LA
   Burke, J
   Lopez, FJ
   Engles, M
AF Rajagopalan, Lakshmi
   Ghosn, Corine
   Tamhane, Mitalee
   Almazan, Alexandra
   Andrews-Jones, Lydia
   Kulkarni, Ashutosh
   Christie, Lori-Ann
   Burke, James
   Lopez, Francisco J.
   Engles, Michael
TI A nonhuman primate model of blue light-induced progressive outer retina
   degeneration showing brimonidine drug delivery system-mediated cyto-and
   neuroprotection
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Nonhuman primate model; Geographic atrophy; Retinal degeneration; Blue
   light irradiation; Brimonidine; Brimo DDS; Cytoprotection;
   Neuroprotection
ID AGE-RELATED MACULOPATHY; ONSET MACULAR DEGENERATION; FUNDUS
   AUTOFLUORESCENCE; GEOGRAPHIC ATROPHY; PATTERNS; SUNLIGHT; AGONISTS;
   DISEASE; LESIONS; MONKEY
AB Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) characterized by atrophy of the retinal pigment epithelium (RPE), loss of photoreceptors, and disruption of choriocapillaris. Excessive light exposure is toxic to the retina and is a known risk factor for AMD. We first investigated the effects of blue light-induced phototoxicity on RPE and photoreceptors in nonhuman primates (NHPs, a model of progressive retinal degeneration) and then evaluated the potential cyto- and neuroprotective effects of the brimonidine drug delivery system (Brimo DDS). In the first set of experiments related to model development, parafoveal lesions of varying severity were induced using blue light irradiation of the retina of cynomolgus monkeys to evaluate the level of phototoxicity in the RPE and photoreceptors. RPE damage was assessed using fundus autofluorescence imaging to quantify areas of hypofluorescence, while thinning of the outer nuclear layer (ONL, photoreceptor nuclei) was quantified using optical coherence tomography (OCT). Photoreceptor function was assessed using multifocal electroretinography (mfERG). RPE damage progressively increased across all lesion severities from 2 to 12 weeks, as did the extent of ONL thinning. Lesions of high severity continued to show reduction in mfERG amplitude, reaching a statistically significant maximum reduction at 12 weeks. Collectively, the first set of experiments showed that blue light irradiation of the NHP eye resulted in progressive retinal degeneration identified by damage to RPE, ONL thinning, and disrupted photoreceptor function - hallmarks of GA in humans. We then used the model to evaluate the cyto- and neuroprotective effects of Brimo DDS, administered as a therapeutic after allowing the lesions to develop for 5 weeks. Placebo DDS or Brimo DDS were administered intravitreally and a set of untreated animals were used as an additional control. In the placebo DDS group, hypofluorescence area continued to increase from baseline, indicating progressive RPE damage, while progression was significantly slowed in eyes receiving Brimo DDS. Likewise, ONL thinning continued to progress over time in eyes that received the placebo DDS, but was reduced in Brimo DDS-treated eyes. Pharmacologically relevant brimonidine concentrations were sustained in the retina for up to 26 weeks following Brimo DDS administration. In summary, Brimo DDS demonstrated cyto- and neuroprotective effects in a novel NHP GA model of progressive retinal degeneration.
C1 [Rajagopalan, Lakshmi; Ghosn, Corine; Tamhane, Mitalee; Almazan, Alexandra; Andrews-Jones, Lydia; Kulkarni, Ashutosh; Christie, Lori-Ann; Burke, James; Lopez, Francisco J.; Engles, Michael] Allergan, 2525 Dupont Dr, Irvine, CA 92612 USA.
C3 AbbVie; Allergan
RP Engles, M (通讯作者)，Allergan, 2525 Dupont Dr, Irvine, CA 92612 USA.
EM michael.engles@abbvie.com
OI Rajagopalan, Lakshmi Priya/0000-0001-9719-2368; Andrews-Jones,
   Lydia/0000-0001-7680-4038
FU Allergan
FX This study was sponsored by Allergan (prior to acquisition by AbbVie
   Inc., North Chicago, IL, USA) . All authors met the ICMJE authorship
   criteria. Neither honoraria nor payments were made for authorship.
   Writing and editorial assistance was provided to the authors by Nayna
   Sanathara, Ph.D., AbbVie Inc. The sponsor and authors would like to
   thank Sara Cabrera-Ghayouri, Movses Karakhosian, Kaveh Azartash, Lupe
   Ruiz, Daniel Gil, and Larry Wheeler for their contributions to this
   work.
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NR 44
TC 2
Z9 2
U1 1
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD AUG
PY 2021
VL 209
AR 108678
DI 10.1016/j.exer.2021.108678
EA JUN 2021
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WC6JU
UT WOS:000704363300004
PM 34153289
OA hybrid
DA 2022-11-30
ER

PT J
AU Cui, RZ
   Tian, LJ
   Lu, D
   Li, HY
   Cui, J
AF Cui, Renzhe
   Tian, Lianji
   Lu, Di
   Li, Huiying
   Cui, Jun
TI Exendin-4 Protects Human Retinal Pigment Epithelial Cells from
   H2O2-Induced Oxidative Damage via Activation of NRF2 Signaling
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Exendin-4; Age-related macular degeneration; Oxidative damage; Nuclear
   factor erythroid 2-related factor-2; Retinal pigment epithelial cell
ID ISCHEMIA-REPERFUSION INJURY; STRESS; APOPTOSIS; PATHWAY; GLP-1; RPE
AB Aims: Oxidative damage plays a vital role in the pathogenesis of age-related macular degeneration (AMD). Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, possesses several pharmacological functions, such as anti-inflammatory and antioxidative properties. However, the effects and mechanism of EX4 on oxidative stress in retinal pigment epithelial (RPE) cells induced by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) remain unclear. The present study aimed to investigate the protective mechanism of EX4 on human RPE cells subjected to oxidative stress. Methods: Human RPE ARPE-19 cells were treated with H<sub>2</sub>O<sub>2</sub> to induce oxidative damage. Cell viability was determined by Cell Counting Kit-8 and lactate dehydrogenase assay. Levels of intracellular reactive oxygen species (ROS), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH) were measured using commercial kits. The expression of nuclear factor erythroid 2-related factor-2 (NRF2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1) was measured using reverse transcription quantitative polymerase chain reaction assay and western blot, respectively. Results: H<sub>2</sub>O<sub>2</sub> significantly induced oxidative stress to reduce viability of RPE cells and increased intracellular ROS generation. EX4 significantly ameliorated H<sub>2</sub>O<sub>2</sub>-induced oxidative damage by reducing intracellular ROS generation, decreasing MDA concentration, and increasing antioxidant enzymes activities (SOD and GSH). In addition, EX4 markedly increased expression of NRF2, HO-1, and NQO-1 and significantly improved protein expression of NRF2 and HO-1 in H<sub>2</sub>O<sub>2</sub>-treated ARPE-19 cells, caused by increased nuclear NRF2 protein expression. NRF2 knockdown by targeted siRNA alleviated EX4-mediated HO-1 expression and significantly nullified EX4-mediated RPE cell protection against H<sub>2</sub>O<sub>2</sub>. Conclusions: EX4 attenuated oxidative damage induced by H<sub>2</sub>O<sub>2</sub> in ARPE-19 cells through the activation of the NRF2 signaling pathway. The findings suggested that EX4 may be a potential therapeutic agent for the treatment of AMD.
C1 [Cui, Renzhe; Tian, Lianji; Lu, Di; Cui, Jun] Yanbian Univ, Affiliated Hosp, Dept Ophthalmol, 1327 Juzi St, Yanji 133000, Jilin, Peoples R China.
   [Li, Huiying] Yanbian Univ, Affiliated Hosp, Dept Nephrol, Yanji, Peoples R China.
   [Li, Huiying; Cui, Jun] Yanbian Univ, Affiliated Hosp, Postdoctoral Res Stn, Yanji, Peoples R China.
C3 Yanbian University; Yanbian University; Yanbian University
RP Li, HY; Cui, J (通讯作者)，Yanbian Univ, Affiliated Hosp, Dept Ophthalmol, 1327 Juzi St, Yanji 133000, Jilin, Peoples R China.
EM 15604332375@163.com; 13009082375@163.com
FU Natural Science Foundation of China [81760132]
FX This study was financially supported by the Natural Science Foundation
   of China (81760132).
CR Baggio LL, 2007, GASTROENTEROLOGY, V132, P2131, DOI 10.1053/j.gastro.2007.03.054
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NR 32
TC 12
Z9 12
U1 0
U2 12
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PD JUL
PY 2020
VL 63
IS 4
BP 404
EP 412
DI 10.1159/000504891
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PI3LW
UT WOS:000600997000005
PM 31865348
DA 2022-11-30
ER

PT J
AU Mishra, S
   Peterson, K
   Yin, LL
   Berger, A
   Fan, JG
   Wistow, G
AF Mishra, Sanghamitra
   Peterson, Katherine
   Yin, Lili
   Berger, Alan
   Fan, Jianguo
   Wistow, Graeme
TI Accumulation of cholesterol and increased demand for zinc in
   serum-deprived RPE cells
SO MOLECULAR VISION
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; LOW-DENSITY LIPOPROTEIN; MACULAR
   DEGENERATION; OXIDATIVE STRESS; GENE-EXPRESSION; FINGER PROTEIN;
   MEMBRANE; BINDING; MICRODOMAINS; GLIS2
AB Purpose: Having observed that confluent ARPE-19 cells (derived from human RPE) survive well in high-glucose serum-free medium (SFM) without further feeding for several days, we investigated the expression profile of RPE cells under the same conditions.
   Methods: Expression profiles were examined with microarray and quantitative PCR (qPCR) analyses, followed by western blot analysis of key regulated proteins. The effects of low-density lipoprotein (LDL) and zinc supplementation were examined with qPCR. Immunofluorescence was used to localize the LDL receptor and to examine LDL uptake. Cellular cholesterol levels were measured with filipin binding. Expression patterns in primary fetal RPE cells were compared using qPCR.
   Results: Microarray analyses of gene expression in ARPE-19, confirmed with qPCR, showed upregulation of lipid and cholesterol biosynthesis pathways in SFM. At the protein level, the cholesterol synthesis control factor SRBEF2 was activated, and other key lipid synthesis proteins increased. Supplementation of SFM with LDL reversed the upregulation of lipid and cholesterol synthesis genes, but not of cholesterol transport genes. The LDL receptor relocated to the plasma membrane, and LDL uptake was activated by day 5-7 in SFM, suggesting increased demand for cholesterol. Confluent ARPE-19 cells in SFM accumulated intracellular cholesterol, compared with cells supplemented with serum, over 7 days. Over the same time course in SFM, the expression of metallothioneins decreased while the major zinc transporter was upregulated, consistent with a parallel increase in demand for zinc. Supplementation with zinc reversed expression changes for metallothionein genes, but not for other zinc-related genes. Similar patterns of regulation were also seen in primary fetal human RPE cells in SFM.
   Conclusions: ARPE-19 cells respond to serum deprivation and starvation with upregulation of the lipid and cholesterol pathways, accumulation of intracellular cholesterol, and increased demand for zinc. Similar trends are seen in primary fetal RPE cells. Cholesterol accumulation basal to RPE is a prominent feature of age-related macular degeneration (AMD), while dietary zinc is protective. It is conceivable that accumulating defects in Bruch's membrane and dysfunction of the choriocapillaris could impede transport between RPE and vasculature in AMD. Thus, this pattern of response to serum deprivation in RPE-derived cells may have relevance for some aspects of the progression of AMD.
C1 [Mishra, Sanghamitra; Peterson, Katherine; Yin, Lili; Fan, Jianguo; Wistow, Graeme] NEI, Sect Mol Struct & Funct Genom, NIH, Bldg 6 Room 106, Bethesda, MD 20892 USA.
   [Berger, Alan] Johns Hopkins Univ, Sch Med, Lowe Family Genom Core, Baltimore, MD USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); Johns Hopkins University
RP Wistow, G (通讯作者)，NEI, Sect Mol Struct & Funct Genom, NIH, Bldg 6 Room 106, Bethesda, MD 20892 USA.
EM graeme@helix.nih.gov
FU Intramural Program of the National Eye Institute, National Institutes of
   Health USA; NATIONAL EYE INSTITUTE [ZIAEY000433] Funding Source: NIH
   RePORTER
FX We thank Drs. Chun Gao and Maria Campos of NEI for expert help with
   microscopy and Dr. Cynthia Jaworski for helpful comments. We thank the
   laboratory of Dr. Sheldon Miller for human primary cells. This work was
   performed with support from the Intramural Program of the National Eye
   Institute, National Institutes of Health USA.
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NR 68
TC 4
Z9 4
U1 2
U2 4
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD DEC 10
PY 2016
VL 22
BP 1387
EP 1404
PG 18
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA EK4PJ
UT WOS:000393908800001
PM 28003730
DA 2022-11-30
ER

PT J
AU Singhal, A
   Simmons, M
   Lu, ZY
AF Singhal, Ayush
   Simmons, Michael
   Lu, Zhiyong
TI Text Mining Genotype-Phenotype Relationships from Biomedical Literature
   for Database Curation and Precision Medicine
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID GENETIC-VARIANTS; MANUAL CURATION; MUTATION; IDENTIFICATION;
   NORMALIZATION; EXTRACTION; SEQUENCES; DISEASES; IMPACT; CANCER
AB The practice of precision medicine will ultimately require databases of genes and mutations for healthcare providers to reference in order to understand the clinical implications of each patient's genetic makeup. Although the highest quality databases require manual curation, text mining tools can facilitate the curation process, increasing accuracy, coverage, and productivity. However, to date there are no available text mining tools that offer high-accuracy performance for extracting such triplets from biomedical literature. In this paper we propose a high-performance machine learning approach to automate the extraction of disease-gene-variant triplets from biomedical literature. Our approach is unique because we identify the genes and protein products associated with each mutation from not just the local text content, but from a global context as well (from the Internet and from all literature in PubMed). Our approach also incorporates protein sequence validation and disease association using a novel text-mining-based machine learning approach. We extract disease-gene-variant triplets from all abstracts in PubMed related to a set of ten important diseases (breast cancer, prostate cancer, pancreatic cancer, lung cancer, acute myeloid leukemia, Alzheimer's disease, hemochromatosis, age-related macular degeneration (AMD), diabetes mellitus, and cystic fibrosis). We then evaluate our approach in two ways: (1) a direct comparison with the state of the art using benchmark datasets; (2) a validation study comparing the results of our approach with entries in a popular human-curated database (UniProt) for each of the previously mentioned diseases. In the benchmark comparison, our full approach achieves a 28% improvement in F-1-measure (from 0.62 to 0.79) over the state-of-the-art results. For the validation study with UniProt Knowledgebase (KB), we present a thorough analysis of the results and errors. Across all diseases, our approach returned 272 triplets (disease-gene-variant) that overlapped with entries in UniProt and 5,384 triplets without overlap in UniProt. Analysis of the overlapping triplets and of a stratified sample of the nonoverlapping triplets revealed accuracies of 93% and 80% for the respective categories (cumulative accuracy, 77%). We conclude that our process represents an important and broadly applicable improvement to the state of the art for curation of disease-gene-variant relationships.
C1 [Singhal, Ayush; Simmons, Michael; Lu, Zhiyong] NIH, NCBI, NLM, Bldg 10, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Library of
   Medicine (NLM)
RP Lu, ZY (通讯作者)，NIH, NCBI, NLM, Bldg 10, Bethesda, MD 20892 USA.
EM zhiyong.lu@nih.gov
RI singhal, ayush/M-3579-2014
OI singhal, ayush/0000-0002-2378-3795
FU NIH Intramural Research Program; National Library of Medicine; NIH
   Medical Research Scholars Program; NIH; NATIONAL LIBRARY OF MEDICINE
   [ZIALM091813] Funding Source: NIH RePORTER
FX This research was supported by the NIH Intramural Research Program,
   National Library of Medicine and the NIH Medical Research Scholars
   Program, a public-private partnership supported jointly by the NIH and
   generous contributions to the Foundation for the NIH from the Doris Duke
   Charitable Foundation, the Howard Hughes Medical Institute, the American
   Association for Dental Research, the Colgate-Palmolive Company, and
   other private donors. No funds from the Doris Duke Charitable Foundation
   were used to support research that used animals. The funders had no role
   in study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 45
TC 63
Z9 64
U1 0
U2 22
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD NOV
PY 2016
VL 12
IS 11
AR e1005017
DI 10.1371/journal.pcbi.1005017
PG 19
WC Biochemical Research Methods; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA EG7MC
UT WOS:000391230900002
PM 27902695
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Yashkin, AP
   Hahn, P
   Sloan, FA
AF Yashkin, Arseniy P.
   Hahn, Paul
   Sloan, Frank A.
TI Introducing Anti-Vascular Endothelial Growth Factor Therapies for AMD
   Did Not Raise Risk of Myocardial Infarction, Stroke, and Death
SO OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; SYSTEMIC SAFETY; SERIES ANALYSIS; FACTOR AGENTS;
   EVENTS; METAANALYSIS; RANIBIZUMAB; MORTALITY; BLINDNESS; DISEASE
AB Purpose: To assess the effect of availability of anti-vascular endothelial growth factor (VEGF) therapy on mortality and hospitalizations for acute myocardial infarction (AMI) and stroke over a 5-year follow-up period in United States Medicare beneficiaries newly diagnosed with exudative age-related macular degeneration (AMD) in 2006 compared with control groups consisting of beneficiaries (1) newly diagnosed with exudative AMD at a time when anti-VEGF therapy was not possible and (2) newly diagnosed with nonexudative AMD.
   Design: Retrospective cohort study.
   Participants: Beneficiaries newly diagnosed with exudative and nonexudative AMD in 2000 and 2006 selected from a random longitudinal sample of Medicare 5% claims and enrollment files.
   Methods: Beneficiaries with a first diagnosis of exudative AMD in 2006 were the treatment group; beneficiaries newly diagnosed with exudative AMD in 2000 or nonexudative AMD in 2000 or 2006 were control groups. To deal with potential selection bias, we designed an intent-to-treat study, which controlled for nonadherence to prescribed regimens. The treatment group consisted of patients with clinically appropriate characteristics to receive anti-VEGF injections given that the therapy is available, bypassing the need to monitor whether treatment was actually received. Control groups consisted of patients with clinically appropriate characteristics but first diagnosed at a time when the therapy was unavailable (2000) and similar patients but for whom the therapy was not clinically indicated (2000, 2006). We used a Cox proportional hazard model.
   Main Outcome Measures: All-cause mortality and hospitalization for AMI and stroke during follow-up.
   Results: No statistically significant changes in probabilities of death and hospitalizations for AMI and stroke within a 5-year follow-up period were identified in exudative AMD beneficiaries newly diagnosed in 2006, the beginning of widespread anti-VEGF use, compared with 2000. As an alternative to our main analysis, which excluded beneficiaries from nonexudative AMD group who received anti-VEGF therapies during follow-up, we performed a sensitivity analysis with this group of individuals reincluded (11% of beneficiaries newly diagnosed with nonexudative AMD in 2006). Results were similar.
   Conclusions: Introduction of anti-VEGF agents in 2006 for treating exudative AMD has not posed a threat of increased risk of AMI, stroke, or all-cause mortality. (C) 2016 by the American Academy of Ophthalmology.
C1 [Yashkin, Arseniy P.; Sloan, Frank A.] Duke Univ, Dept Econ, 213 Social Sci Bldg,Box 90097, Durham, NC 27708 USA.
   [Hahn, Paul] NJRetina, Morristown, NJ USA.
C3 Duke University
RP Sloan, FA (通讯作者)，Duke Univ, Dept Econ, 213 Social Sci Bldg,Box 90097, Durham, NC 27708 USA.
EM fsloan@duke.edu
RI Yashkin, Arseniy/AAT-4613-2020
FU National Institute on Aging [R01-AG017473]; NATIONAL INSTITUTE ON AGING
   [R01AG017473] Funding Source: NIH RePORTER
FX Supported in part by the National Institute on Aging (grant
   R01-AG017473). The sponsor or funding organization had no role in the
   design or conduct of this research.
CR Alexander SL, 2007, OPHTHALMOLOGY, V114, P2174, DOI 10.1016/j.ophtha.2007.09.017
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NR 27
TC 16
Z9 16
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD OCT
PY 2016
VL 123
IS 10
BP 2225
EP 2231
DI 10.1016/j.ophtha.2016.06.053
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EE3QI
UT WOS:000389509100021
PM 27523614
OA Green Accepted, Green Published
DA 2022-11-30
ER

PT J
AU Qu, ZP
   Guan, Y
   Cui, L
   Song, J
   Gu, JJ
   Zhao, HZ
   Xu, L
   Lu, LX
   Jin, Y
   Xu, GT
AF Qu, Zepeng
   Guan, Yuan
   Cui, Lu
   Song, Jian
   Gu, Junjie
   Zhao, Hanzhi
   Xu, Lei
   Lu, Lixia
   Jin, Ying
   Xu, Guo-Tong
TI Transplantation of rat embryonic stem cell-derived retinal progenitor
   cells preserves the retinal structure and function in rat retinal
   degeneration
SO STEM CELL RESEARCH & THERAPY
LA English
DT Article
DE Rat embryonic stem cell; Degenerative retinal diseases; Retinal
   progenitor cell (RPC); Transplantation; Royal College of Surgeons (RCS)
   rat
ID IN-VITRO DIFFERENTIATION; HUMAN NEURAL PROGENITORS; LONG-TERM
   PRESERVATION; ERG B-WAVE; RCS RATS; MACULAR DEGENERATION;
   RETINITIS-PIGMENTOSA; VISUAL FUNCTION; PHOTORECEPTOR PRECURSORS;
   CORTICAL TISSUES
AB Introduction: Degenerative retinal diseases like age-related macular degeneration (AMD) are the leading cause of blindness. Cell transplantation showed promising therapeutic effect for such diseases, and embryonic stem cell (ESC) is one of the sources of such donor cells. Here, we aimed to generate retinal progenitor cells (RPCs) from rat ESCs (rESCs) and to test their therapeutic effects in rat model.
   Methods: The rESCs (DA8-16) were cultured in N2B27 medium with 2i, and differentiated to two types of RPCs following the SFEBq method with modifications. For rESC-RPC1, the cells were switched to adherent culture at D10, while for rESC-RPC2, the suspension culture was maintained to D14. Both RPCs were harvested at D16. Primary RPCs were obtained from P1 SD rats, and some of them were labeled with EGFP by infection with lentivirus. To generate Rax::EGFP knock-in rESC lines, TALENs were engineered to facilitate homologous recombination in rESCs, which were cotransfected with the targeting vector and TALEN vectors. The differentiated cells were analyzed with live image, immunofluorescence staining, flow cytometric analysis, gene expression microarray, etc. RCS rats were used to mimic the degeneration of retina and test the therapeutic effects of subretinally transplanted donor cells. The structure and function of retina were examined.
   Results: We established two protocols through which two types of rESC-derived RPCs were obtained and both contained committed retina lineage cells and some neural progenitor cells (NPCs). These rESC-derived RPCs survived in the host retinas of RCS rats and protected the retinal structure and function in early stage following the transplantation. However, the glia enriched rESC-RPC1 obtained through early and longer adherent culture only increased the b-wave amplitude at 4 weeks, while the longer suspension culture gave rise to evidently neuronal differentiation in rESC-RPC2 which significantly improved the visual function of RCS rats.
   Conclusions: We have successfully differentiated rESCs to glia enriched RPCs and retinal neuron enriched RPCs in vitro. The retinal neuron enriched rESC-RPC2 protected the structure and function of retina in rats with genetic retinal degeneration and could be a candidate cell source for treating some degenerative retinal diseases in human trials.
C1 [Qu, Zepeng; Guan, Yuan; Cui, Lu; Jin, Ying] Shanghai Jiao Tong Univ, Sch Med, Lab Mol Dev Biol, Shanghai 200025, Peoples R China.
   [Lu, Lixia; Xu, Guo-Tong] Shanghai Tenth Peoples Hosp, Dept Ophthalmol, Shanghai 200092, Peoples R China.
   [Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Lab Clin Visual Sci, Tongji Eye Inst, Shanghai 200092, Peoples R China.
   [Gu, Junjie; Zhao, Hanzhi; Jin, Ying] Shanghai Jiao Tong Univ, Chinese Acad Sci, Key Lab Stem Cell Biol, Inst Hlth Sci,Shanghai Inst Biol Sci,Sch Med, Shanghai 200031, Peoples R China.
   [Song, Jian; Jin, Ying] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China.
   [Xu, Lei; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Stem Cell Res Ctr, Dept Regenerat Med, Shanghai 200092, Peoples R China.
   [Xu, Lei; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Inst Nutr Sci, Shanghai 200092, Peoples R China.
C3 Shanghai Jiao Tong University; Tongji University; Chinese Academy of
   Sciences; Shanghai Institutes for Biological Sciences, CAS; Shanghai
   Jiao Tong University; ShanghaiTech University; Tongji University;
   Chinese Academy of Sciences; Tongji University
RP Jin, Y (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Lab Mol Dev Biol, Room 208,Bldg 5,280 South Chongqing Rd, Shanghai 200025, Peoples R China.
EM yjin@sibs.ac.cn; gtxu@tongji.edu.cn
RI Qu, Zepeng/GYJ-3779-2022; Guan, Yuan/B-4986-2019
FU China National High-Tech R&D Program (863 program); National Key Basic
   Research Program (973 Program) [2013AA020109, 2013CB966801,
   2012AA020906, 2011CB965102, 2013CB967500, 2012CBA01308]; National
   Natural Science Foundation of China [31171419]
FX This work was supported by the following grants: China National
   High-Tech R&D Program (863 program) and National Key Basic Research
   Program (973 Program): (2013AA020109, 2013CB966801, 2012AA020906,
   2011CB965102, 2013CB967500, 2012CBA01308) as well as National Natural
   Science Foundation of China (31171419).
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NR 99
TC 19
Z9 21
U1 0
U2 22
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1757-6512
J9 STEM CELL RES THER
JI Stem Cell Res. Ther.
PD NOV 9
PY 2015
VL 6
AR 219
DI 10.1186/s13287-015-0207-x
PG 19
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA CV5CT
UT WOS:000364284700001
PM 26553210
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ziemssen, F
   Luke, M
   Bartz-Schmidt, KU
   Gelisken, F
AF Ziemssen, Focke
   Lueke, Matthias
   Bartz-Schmidt, Karl U.
   Gelisken, Faik
TI Time-dependent effects on contrast sensitivity, near and distance
   acuity: difference in functional parameters? (Prospective, randomized
   pilot trial of photodynamic therapy versus full macular translocation)
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; contrast sensitivity; full macular
   translocation; near vision; photodynamic therapy; visual acuity; surgery
ID QUALITY-OF-LIFE; VISUAL FUNCTION; DEGENERATION; VERTEPORFIN; DISABILITY;
   SURGERY; PEOPLE
AB Purpose To report the change of contrast sensitivity (CS) after photodynamic therapy (PDT) vs full macular translocation (FMT) for neovascular age-related macular degeneration (AMD), and to relate this to other measures of visual function (distance and near acuity).
   Methods Fifty patients (50 eyes) with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to AMD were randomized to PDT or FMT. CS was measured with Pelli-Robson charts. Acuity scores of near visual function (NVS) were calculated after testing with visual acuity cards of the Swiss National Association of and for the Blind (SNAB). Best corrected distance visual acuity (DVA) was determined according to a standardized protocol with EDTRS charts. Primary end point was the change of CS at 12-month examination from baseline. The interaction of the CS with NVS and DVA was analysed.
   Results Mean CS showed a decrease in both treatment groups (FMT: -2 letters, PDT: -3 letters, p = 0.969) at 12-month examination from baseline. While mean NVS improved by seven letters in the FMT group, a decrease of more than ten letters was seen in the PDT group (p < 0.05). We found no agreement between CS and high-contrast acuity (NVS, DVA). In FMT patients, the parameters at baseline (CS, NVS, DVA) correlated poorly with the corresponding 12-month results, therefore providing no informative basis to predict the later functional development. In contrast, PDT patients showed strong baseline-to-outcome coherence with baseline measures also associated with better final values.
   Conclusions Although FMT can initiate recovery of near and distance acuity over the period of 1 year in selected patients with classic CNV, CS did not differ between FMT and PDT. We found no close connection of CS with DVA or NVS, especially after FMT. Knowledge about the unequal variation of visual parameters can provide more comprehensive information when advising patients on different therapeutic options. That also applies in particular to vascular endothelial growth factor inhibitors, which seem to promise an even higher extent of gain in CS and to reach the peak of recovery at an earlier time.
C1 [Ziemssen, Focke; Lueke, Matthias; Bartz-Schmidt, Karl U.; Gelisken, Faik] Univ Tubingen, Univ Eye Hosp, Dept Ophthalmol, D-72076 Tubingen, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital
RP Ziemssen, F (通讯作者)，Univ Tubingen, Univ Eye Hosp, Dept Ophthalmol, Schleichstr 12-16, D-72076 Tubingen, Germany.
EM focke.ziemssen@med.uni-tuebingen.de
RI , Ziemssen/B-9564-2009; Ziemssen, Focke/AAY-1686-2021
OI , Ziemssen/0000-0002-3873-0581; 
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NR 27
TC 8
Z9 9
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD MAY
PY 2008
VL 246
IS 5
BP 653
EP 659
DI 10.1007/s00417-007-0726-y
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 285JO
UT WOS:000254773300005
PM 18071731
DA 2022-11-30
ER

PT J
AU Dutt, K
   Harris-Hooker, S
   Ellerson, D
   Layne, D
   Kumar, R
   Hunt, R
AF Dutt, K
   Harris-Hooker, S
   Ellerson, D
   Layne, D
   Kumar, R
   Hunt, R
TI Generation of 3D retina-like structures from a human retinal cell line
   in a NASA bioreactor
SO CELL TRANSPLANTATION
LA English
DT Article
DE tissue engineering; bioreactor; human retinal precursors; neurons;
   photoreceptors
ID ROTATING-WALL VESSEL; 3-DIMENSIONAL GROWTH; EMBRYONIC RETINA;
   PHOTORECEPTOR TRANSPLANTATION; SIMULATED MICROGRAVITY; SHEAR-STRESS;
   GENE; DIFFERENTIATION; EXPRESSION; ESTABLISHMENT
AB Replacement of damaged cells is a promising approach for treatment of age-related macular degeneration (AMD) and retinitis pigmentosa (RP); however, availability of donor tissue for transplantation remains a major obstacle. Key factors for successful engineering of a tissue include the identification of a neural cell line that is: homogeneous but can be expanded to give rise to multiple cells types; is nontumorigenic, yet capable of secreting neurotrophic factors; and is able to form three-dimensional (3D), differentiated structures. The goal of this study was to test the feasibility of tissue engineering from a multipotential human retinal cell line using a NASA-developed bioreactor. A multipotential human retinal precursor cell line was used to generate 3D structures. In addition, retinal pigment epithelium (RPE) cells were cocultured with neural cells to determine if 3D retinal structures could be generated in the bioreactor with cells grown on laminin-coated cytodex 3 beads. Cell growth, morphology, and differentiation were monitored by light and scanning electron microscopy, Western blot analysis, and analysis of glucose use and lactate production. The neuronal retinal precursor cell line cultured in a bioreactor gave rise to most retinal cell types seen in monolayer culture. They formed composite structures with cell-covered beads associated with one another in a tissue-like array. The beginning of layering and/or separation of cell types was observed. The neuronal cell types previously seen in monolayer cultures were also seen in the bioreactor. Some of the retinal cells differentiate into photoreceptors in the bioreactor with well-developed outer segment-like structures, a process that is critical for retinal function. Moreover, the neuronal cells that were generated resembled their in vivo phenotype more closely than those grown under other conditions. Outer segments were almost never seen in the monolayer cultures, even in the presence of photoreceptor-inducing growth factors such as basic fibroblast growth factor (bFGF) and transforming growth factor (TGF-alpha). Muller cells were occasionally seen when retinal, RPE cells were cocultured with retinal cells in the bioreactor. These have never been seen in this retinal cell line before. Cells grown in the bioreactor expressed several proteins specific for the retinal cell types: opsin, protein kinase C-alpha, dopamine receptor D-4, tyrosine hydroxylase, and calbindin.
C1 Morehouse Sch Med, Dept Pathol, Atlanta, GA 30310 USA.
   Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA.
   Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA.
   Univ S Carolina, Sch Med, Dept Microbiol, Columbia, SC USA.
C3 Morehouse School of Medicine; Morehouse School of Medicine; Morehouse
   School of Medicine; University of South Carolina; University of South
   Carolina System; University of South Carolina Columbia
RP Dutt, K (通讯作者)，Morehouse Sch Med, Dept Pathol, 720 Westview Dr SW, Atlanta, GA 30310 USA.
EM duttk@msm.edu
FU NATIONAL EYE INSTITUTE [R01EY010516] Funding Source: NIH RePORTER; NEI
   NIH HHS [EY10516] Funding Source: Medline
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NR 54
TC 25
Z9 30
U1 0
U2 15
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0963-6897
EI 1555-3892
J9 CELL TRANSPLANT
JI Cell Transplant.
PY 2003
VL 12
IS 7
BP 717
EP 731
DI 10.3727/000000003108747334
PG 15
WC Cell & Tissue Engineering; Medicine, Research & Experimental;
   Transplantation
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine; Transplantation
GA 743VQ
UT WOS:000186594600006
PM 14653619
OA Bronze
DA 2022-11-30
ER

PT J
AU Pal, MN
   Roy, S
   Banerjee, M
AF Nandy Pal, Mahua
   Roy, Shuvankar
   Banerjee, Minakshi
TI Content based retrieval of retinal OCT scans using twin CNN
SO SADHANA-ACADEMY PROCEEDINGS IN ENGINEERING SCIENCES
LA English
DT Article
DE Retinal OCT scan; diabetic macular edema (DME); age related macular
   degeneration (AMD); convolutional neural network (CNN); mean average
   precision (MAP); mean reciprocal rank (MRR)
ID DIABETIC MACULAR EDEMA; DEGENERATION
AB Retinal imaging helps to detect retinal and cardiovascular abnormalities. Among these abnormalities, Diabetic Macular Edema (DME) and Age Related Macular Degeneration (AMD), both are frequent retinal degenerative diseases leading to blindness. Content based retinal OCT scan retrieval process makes use of characteristic features to retrieve similar Optical Coherent Tomography (OCT) scans, index-wise, from a database with minimal human intervention. A number of existing methods take care of segmentation and identification of retinal landmarks and pathologies from OCT volumes. As per the literature survey, till date, no papers are there which deal with the retrieval of retinal OCT scans. In this work, we propose a retrieval system for retinal OCT scans which extracts feature maps of both query and database samples from the layer of deep convolutional neural network and compares for their similarity. The Twin network comparison approach exploits deep features without the resource, space and computation exhaustive network training phase. Most of the techniques involving deep network implementation suffer from the drawbacks of data augmentation and resizing. These requirements have been eliminated automatically as part of the Twin network implementation procedure. The system successfully retrieves retinas with similar symptoms from the database of differently affected and unaffected OCT scans. We evaluated different variations of retrieval performances like AMD-Normal, DME-Normal, AMD-DME, AMD-DME-Normal, etc. Execution time optimization has also been achieved as the network used is comparatively shallow and network training is not required. The system retrieves similar scans from a dataset of abnormal and normal OCT scans with a mean average precision of 0.7571 and mean reciprocal rank of 0.9050. Considering all possible variations of retrieval, we achieved overall mean average precision and mean reciprocal rank of 0.631167 and 0.829607, respectively which are also quite notable with rank thresholds of 3, 5 and 7. Experiments show that the method is noticeably successful in retrieving similar OCT volumes. Per image mean average retrieval time is 8.3 sec. Automatic retrieval of retinal OCT volumes for the presence of a particular ailment can help ophthalmologists in the mass screening process.
C1 [Nandy Pal, Mahua; Roy, Shuvankar] MCKV Inst Engn, CSE Dept, Howrah 711204, W Bengal, India.
   [Banerjee, Minakshi] RCC Inst Informat Technol, CSE Dept, Kolkata 700015, W Bengal, India.
C3 RCC Institute of Information Technology (RCCIIT)
RP Pal, MN (通讯作者)，MCKV Inst Engn, CSE Dept, Howrah 711204, W Bengal, India.
EM mahua.nandy@gmail.com; shuvankarroy2@gmail.com; mbanerjee23@gmail.com
RI Pal, Mahua Nandy/ABE-8564-2021
OI Pal, Mahua Nandy/0000-0002-9633-6718
CR Chung YA, 2017, ARXIV PREPRINT ARXIV
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NR 18
TC 1
Z9 1
U1 0
U2 2
PU SPRINGER INDIA
PI NEW DELHI
PA 7TH FLOOR, VIJAYA BUILDING, 17, BARAKHAMBA ROAD, NEW DELHI, 110 001,
   INDIA
SN 0256-2499
EI 0973-7677
J9 SADHANA-ACAD P ENG S
JI Sadhana-Acad. Proc. Eng. Sci.
PD SEP
PY 2021
VL 46
IS 3
AR 174
DI 10.1007/s12046-021-01701-5
PG 14
WC Engineering, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA UF2ZU
UT WOS:000688447700001
OA Bronze
DA 2022-11-30
ER

PT J
AU Lee, DU
   Huang, WH
   Rittenhouse, KD
   Jessen, B
AF Lee, Dong U.
   Huang, Wenhu
   Rittenhouse, Kay D.
   Jessen, Bart
TI Retina Expression and Cross-Species Validation of Gene Silencing by
   PF-655, a Small Interfering RNA Against RTP801 for the Treatment of
   Ocular Disease
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID MACULAR DEGENERATION; REDD1; ACTIVATION; TOXICITY; HYPOXIA; RABBIT;
   SIRNA; STIMULATION; INHIBITION; TARGET
AB Purpose: PF-655, a synthetic 19-mer siRNA, targeting the RTP801 gene is currently in clinical trials for the treatment of wet age-related macular degeneration and diabetic macular edema. Preclinical studies have shown a dose-related suppression of RTP801 expression in rat disease models. Investigative studies were conducted with PF-655 to validate the Dutch-Belted rabbit as a biologically relevant species for gene silencing to support nonclinical ocular toxicity and continual dosing studies.
   Methods: Cross-species comparison and DNA sequencing was done to determine the level of homology between PF-655 and rabbit RTP801. Human (HEK 293) and rabbit (SIRC cornea) cell lines were stimulated with CoCl2 to mimic hypoxic stress (an inducer of RTP801 expression) and treated with PF-655. Taqman-polymerase chain reaction and immunoblot analysis were performed to gauge RTP801 expression in cell culture and rabbit retinas.
   Results: Sequence analysis showed a 1-base mismatch in the PF-655 targeting site from genomic DNA of Dutch-Belted rabbit and the SIRC cell line, a cornea cell derived from the New Zealand White rabbit. HEK and SIRC CoCl2-stressed cells induced RTP801 expression 10-20-fold above control conditions. Treatment with 20 or 100 nM PF-655 showed a decrease in gene expression, 40%-50% relative to appropriate controls. RTP801 mRNA was detectable in primary rabbit retina tissues, with cycle threshold values showing a large linear range for the assay.
   Conclusion: These results support our investigation into cross-species validation of gene suppression by a therapeutic siRNA designed to a human gene. The SIRC cell line was utilized as a surrogate to test the degree of RTP801 gene silencing induced by PF-655 in vitro. With a 1-base mismatch, the level of silencing in a rabbit ocular cell line was comparable to that of a human cell line. Sequence analysis and expression data confirmed the relevance of the RTP801 target gene in rabbits and the utility of this species as a relevant animal model. Additionally, our work outlines a tractable method that validates relevant larger non-rodent species for ophthalmic drug testing.
C1 [Lee, Dong U.; Huang, Wenhu; Jessen, Bart] Pfizer Global Res & Dev, Drug Safety, San Diego, CA 92121 USA.
   [Rittenhouse, Kay D.] Pfizer Global Res & Dev, Translat Med Ophthalmol, San Diego, CA 92121 USA.
C3 Pfizer; Pfizer
RP Lee, DU (通讯作者)，Pfizer Global Res & Dev, Drug Safety, San Diego, CA 92121 USA.
EM dong.lee2@pfizer.com
RI huang, wen/GXW-0661-2022
FU Pfizer Global Research and Development
FX The study was supported by Pfizer Global Research and Development, and
   all the authors are employees of the company.
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   Sioud M, 2008, FRONT BIOSCI, V13, P4379, DOI 10.2741/3011
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NR 35
TC 15
Z9 16
U1 0
U2 8
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD JUN
PY 2012
VL 28
IS 3
BP 222
EP 230
DI 10.1089/jop.2011.0116
PG 9
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 957EE
UT WOS:000305140700005
PM 22304497
DA 2022-11-30
ER

PT J
AU Prasad, AS
AF Prasad, Ananda S.
TI Zinc in human health: Effect of zinc on immune cells
SO MOLECULAR MEDICINE
LA English
DT Article
ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; IRON DEFICIENCY ANEMIA; FINGER
   PROTEIN; ACTIVATION; SUPPLEMENTATION; A20; ALPHA; EXPRESSION;
   INTERLEUKIN-2
AB Although the essentiality of zinc for plants and animals has been known for many decades, the essentiality of zinc for humans was recognized only 40 years ago in the Middle East. The zinc-deficient patients had severe immune dysfunctions, inasmuch as they died of intercurrent infections by the time they were 25 years of age. In our studies in an experimental human model of zinc deficiency, we documented decreased serum testosterone level, oligospermia, severe immune dysfunctions mainly affecting T helper cells, hyperammonemia, neurosensory disorders, and decreased lean body mass. It appears that zinc deficiency is prevalent in the developing world and as many as two billion subjects may be growth retarded due to zinc deficiency, Besides growth retardation and immune dysfunctions, cognitive impairment due to zinc deficiency also has been reported recently. Our studies in the cell culture models showed that the activation of many zinc-dependent enzymes and transcription factors were adversely affected due to zinc deficiency. In HUT-78 (T helper 0 (Th-0) cell line), we showed that a decrease in gene expression of interleukin-2 (IL-2) and IL-2 receptor a (IL-2R alpha) were due to decreased activation of nuclear factor-kappa B (NF-kappa B) in zinc deficient cells. Decreased NF-kappa B activation in HUT-78 due to zinc deficiency was due to decreased binding of NF-kappa B to DNA, decreased level of NF-kappa B p105 (the precursor of NF-kappa B p50) mRNA, decreased kappa B inhibitory protein (I kappa B) phosphorylation, and decreased I kappa kappa. These effects of zinc were cell specific. Zinc also is an antioxidant and has anti-inflammatory actions. The therapeutic roles of zinc in acute infantile diarrhea, acrodermatitis enteropathica, prevention of blindness in patients with age-related macular degeneration, and treatment of common cold with zinc have been reported. In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway, decreases NF-kappa B activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, and IL-8. We have reported recently that in both young adults and elderly subjects, zinc supplementation decreased oxidative stress markers and generation of inflammatory cytokines.
C1 Wayne State Univ, Sch Med, Detroit, MI 48201 USA.
C3 Wayne State University
RP Prasad, AS (通讯作者)，Wayne State Univ, Sch Med, 1122 Elliman Bldg,421 E Canfield, Detroit, MI 48201 USA.
EM prasada@karmanas.org
RI Ibrahim, Essam Hassan/G-1960-2018
OI Ibrahim, Essam Hassan/0000-0003-0130-2257
FU PHS HHS [5 R01 A150698-04] Funding Source: Medline
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   [No title captured]
NR 39
TC 463
Z9 482
U1 0
U2 63
PU FEINSTEIN INST MED RES
PI MANHASSET
PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA
SN 1076-1551
J9 MOL MED
JI Mol. Med.
PD MAY-JUN
PY 2008
VL 14
IS 5-6
BP 353
EP 357
DI 10.2119/2008-00033.Prasad
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 298WA
UT WOS:000255716600015
PM 18385818
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, SJ
   Zaitoun, IS
   Darjatmoko, SR
   Sheibani, N
   Sorenson, CM
AF Wang, Shoujian
   Zaitoun, Ismail S.
   Darjatmoko, Soesiawati R.
   Sheibani, Nader
   Sorenson, Christine M.
TI Bim Expression Promotes the Clearance of Mononuclear Phagocytes during
   Choroidal Neovascularization, Mitigating Scar Formation in Mice
SO LIFE-BASEL
LA English
DT Article
DE angiogenesis; vascular dysfunction; inflammation; macrophages;
   age-related macular degeneration; choroid; Bcl-2 family
ID CELL-SURVIVAL; INFLAMMATION; MACROPHAGES; ACTIVATION; REGULATORS;
   LETHALITY; INTEGRINS; APOPTOSIS; ARTHRITIS; ADHESION
AB Inflammation is increasingly recognized as an important modulator in the pathogenesis of neovascular age-related macular degeneration (nAMD). Although significant progress has been made in delineating the pathways that contribute to the recruitment of inflammatory cells and their contribution to nAMD, we know little about what drives the resolution of these inflammatory responses. Gaining a better understanding of how immune cells are cleared in the choroid will give a novel insight into how sustained inflammation could influence the pathogenesis of nAMD. The pro-apoptotic Bcl-2 family member Bim is a master regulator of immune cell homeostasis. In its absence, immune cell lifespan and numbers increase. Most therapeutic regimes that squelch inflammation do so by enhancing immune cell apoptosis through enhanced Bim expression and activity. To test the hypothesis that Bim expression tempers inflammation during the pathogenesis of nAMD, we used the mouse laser-induced choroidal neovascularization (CNV) model in which inflammation acts as a facilitator of CNV. Here, we showed minimal to no change in the recruitment of F4/80-, CD80-, CD11b-, and Iba1-positive myeloid-derived mononuclear phagocytes to the site of laser photocoagulation in the absence of Bim expression. However, the resolution of these cells from the choroid of Bim-deficient (Bim -/-) mice was significantly diminished following laser photocoagulation. With time, we noted increased scar formation, demonstrated by collagen I staining, in Bim -/- mice with no change in the resolution of neovascularization compared to wild-type littermates. We also noted that mice lacking Bim expression in mononuclear phagocytes (Bim(Flox/Flox); Lyz2-Cre (Bim(MP)) mice) had delayed resolution of F4/80-, CD80-, CD11b-, and Iba1-positive cells, while those lacking Bim expression in endothelial cells (Bim(Flox/Flox); Cad5-Cre (Bim(EC)) mice) had delayed resolution of only CD11b- and Iba1-positive cells. Both Bim(MP) and Bim(EC) mice demonstrated increased scar formation, albeit to differing degrees. Thus, our studies show that resolving inflammation plays an important role in moderating scar formation in nAMD, and it is impacted by Bim expression in both the endothelium and mononuclear phagocyte lineages.
C1 [Wang, Shoujian; Zaitoun, Ismail S.; Darjatmoko, Soesiawati R.; Sheibani, Nader] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53705 USA.
   [Zaitoun, Ismail S.; Sheibani, Nader; Sorenson, Christine M.] Univ Wisconsin, Sch Med & Publ Hlth, McPherson Eye Res Inst, Madison, WI 53705 USA.
   [Sorenson, Christine M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53705 USA.
C3 University of Wisconsin System; University of Wisconsin Madison;
   University of Wisconsin System; University of Wisconsin Madison;
   University of Wisconsin System; University of Wisconsin Madison
RP Sorenson, CM (通讯作者)，Univ Wisconsin, Sch Med & Publ Hlth, McPherson Eye Res Inst, Madison, WI 53705 USA.; Sorenson, CM (通讯作者)，Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53705 USA.
EM shoujianwang@wisc.edu; iszaitoun@wisc.edu; srdarjat@wisc.edu;
   nsheibanikar@wisc.edu; cmsorenson@wisc.edu
OI Sheibani, Nader/0000-0003-2723-9217
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NR 48
TC 1
Z9 1
U1 1
U2 1
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2075-1729
J9 LIFE-BASEL
JI Life-Basel
PD FEB
PY 2022
VL 12
IS 2
AR 208
DI 10.3390/life12020208
PG 15
WC Biology; Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Microbiology
GA ZN0CW
UT WOS:000764714400001
PM 35207495
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Engel, AL
   Wang, YK
   Khuu, TH
   Worrall, E
   Manson, MA
   Lim, RR
   Knight, K
   Yanagida, A
   Qi, JH
   Ramakrishnan, A
   Weleber, RG
   Klein, ML
   Wilson, DJ
   Anand-Apte, B
   Hurley, JB
   Du, JH
   Chao, JR
AF Engel, Abbi L.
   Wang, YeKai
   Khuu, Thomas H.
   Worrall, Emily
   Manson, Megan A.
   Lim, Rayne R.
   Knight, Kaitlen
   Yanagida, Aya
   Qi, Jian Hua
   Ramakrishnan, Aravind
   Weleber, Richard G.
   Klein, Michael L.
   Wilson, David J.
   Anand-Apte, Bela
   Hurley, James B.
   Du, Jianhai
   Chao, Jennifer R.
TI Extracellular matrix dysfunction in Sorsby patient-derived retinal
   pigment epithelium
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retinal pigment epithelium; Age-related macular degeneration; Induced
   pluripotent stem cells; Basal laminar drusen; Fundus dystrophy
   pseudoinflammatory of Sorsby; CRISPR-Cas9 gene editing
ID TISSUE INHIBITOR; MACULAR DEGENERATION; FUNDUS-DYSTROPHY; BRUCHS
   MEMBRANE; COLLAGEN; TIMP-3; DRUSEN; METALLOPROTEINASES-3;
   DIFFERENTIATION; MUTATION
AB Sorsby Fundus Dystrophy (SFD) is a rare form of macular degeneration that is clinically similar to age-related macular degeneration (AMD), and a histologic hallmark of SFD is a thick layer of extracellular deposits beneath the retinal pigment epithelium (RPE). Previous studies of SFD patient-induced pluripotent stem cell (iPSC) derived RPE differ as to whether these cultures recapitulate this key clinical feature by forming increased drusenoid deposits. The primary purpose of this study is to examine whether SFD patient-derived iPSC-RPE form basal deposits similar to what is found in affected family member SFD globes and to determine whether SFD iPSC RPE may be more oxidatively stressed. We performed a careful comparison of iPSC RPE from three control individuals, multiple iPSC clones from two SFD patients' iPSC RPE, and post-mortem eyes of affected SFD family members. We also examined the effect of CRISPR-Cas9 gene correction of the S204C TIMP3 mutation on RPE phenotype. Finally, targeted metabolomics with liquid chromatography and mass spectrometry analysis and stable isotope-labeled metabolite analysis were performed to determine whether SFD RPE are more oxidatively stressed. We found that SFD iPSC-RPE formed significantly more sub-RPE deposits (similar to 6-90 mu m in height) compared to control RPE at 8 weeks. These deposits were similar in composition to the thick layer of sub-RPE deposits found in SFD family member globes by immunofluorescence staining and TEM imaging. S204C TIMP3 correction by CRISPR-Cas9 gene editing in SFD iPSC RPE cells resulted in significantly reduced basal laminar and sub-RPE calcium deposits. We detected a similar to 18-fold increase in TIMP3 accumulation in the extracellular matrix (ECM) of SFD RPE, and targeted metabolomics showed that intracellular 4-hydroxyproline, a major breakdown product of collagen, is significantly elevated in SFD RPE, suggesting increased ECM turnover. Finally, SFD RPE cells have decreased intracellular reduced glutathione and were found to be more vulnerable to oxidative stress. Our findings suggest that elements of SFD pathology can be demonstrated in culture which may lead to insights into disease mechanisms.
C1 [Engel, Abbi L.; Khuu, Thomas H.; Worrall, Emily; Manson, Megan A.; Lim, Rayne R.; Knight, Kaitlen; Yanagida, Aya; Hurley, James B.; Chao, Jennifer R.] Univ Washington, Dept Ophthalmol, Seattle, WA 98109 USA.
   [Wang, YeKai; Du, Jianhai] West Virginia Univ, Dept Ophthalmol, Morgantown, WV 26506 USA.
   [Wang, YeKai; Du, Jianhai] West Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA.
   [Qi, Jian Hua; Anand-Apte, Bela] Cleveland Clin Fdn, Cole Eye Inst, Dept Ophthalm Res, Cleveland, OH 44106 USA.
   [Ramakrishnan, Aravind] St Davids South Austin Med Ctr, Ctr Blood Canc & Oncol, Austin, TX 78704 USA.
   [Weleber, Richard G.; Klein, Michael L.; Wilson, David J.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
   [Hurley, James B.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; West
   Virginia University; West Virginia University; Cleveland Clinic
   Foundation; Oregon Health & Science University; University of
   Washington; University of Washington Seattle
RP Chao, JR (通讯作者)，750 Republican St,Box 358058, Seattle, WA 98109 USA.; Du, JH (通讯作者)，WVU Eye Inst, One Med Ctr Dr,POB 9193, Morgantown, WV 26505 USA.
EM jianhai.du@wvumedicine.org; jrchao@uw.edu
FU NIH [EY026030, EY06641, EY017863, EY019714, EY001730]; BrightFocus
   Foundation; Illinois No. 3 Foundation; Retinal Research Foundation; Bill
   & Melinda Gates Foundation; Research to Prevent Blindness Sybil B.
   Harrington Physician-Scientist Award for Macular Degeneration; Research
   to Prevent Blindness [EY016490, EY027083, EY020861, P30EY025585]
FX NIH Grants EY026030 (J.D., J.B.H., and J.R.C.), EY06641 (J.B.H.),
   EY017863 (J.B.H.), EY019714 (J.R.C.), and EY001730 (National Eye
   Institute Vision Research Core); BrightFocus Foundation (J.D., J.R.C.);
   Illinois No. 3 Foundation (J.R.C.); Retinal Research Foundation (J.D.);
   the Bill & Melinda Gates Foundation (J.R.C.); Research to Prevent
   Blindness Sybil B. Harrington Physician-Scientist Award for Macular
   Degeneration (J.R.C.), and an unrestricted grant from Research to
   Prevent Blindness (J.R.C.), EY016490 (BA-A), EY027083 (BA-A), EY020861
   (BA-A), and P30EY025585 (Cole Eye Institute).
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NR 45
TC 1
Z9 1
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2022
VL 215
AR 108899
DI 10.1016/j.exer.2021.108899
EA DEC 2021
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YG4TC
UT WOS:000742482100004
PM 34929159
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Chidlow, G
   Plunkett, M
   Casson, RJ
   Wood, JPM
AF Chidlow, Glyn
   Plunkett, Malcolm
   Casson, Robert J.
   Wood, John P. M.
TI Investigations Into Localized Re-Treatment of the Retina With a
   3-Nanosecond Laser
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE age-related macular degeneration; inner retinal neurons; nanosecond
   laser; photoreceptors; retreatment; retina; retinal pigment epithelium
ID INDUCED CHOROIDAL NEOVASCULARIZATION; DIABETIC MACULAR EDEMA; PIGMENT
   EPITHELIUM; CONVENTIONAL PHOTOCOAGULATOR; NANOSECOND; THERAPY;
   DEGENERATION; DAMAGE; PATHOGENESIS; RANIBIZUMAB
AB Background and Objectives: Subvisual retinal lasers necessarily cause clinically invisible lesions, hence, they could intentionally or inadvertently be targeted at precisely the same or an overlapping location during repeat laser treatment. Herein, we investigated the structural integrity and cellular responses of localized re-treatment using a nanosecond laser (2RT) currently in trials for early age-related macular degeneration.
   Materials and Methods: Rats were randomly assigned to one of five groups: sham, subvisual 2RT, subvisual 2RT re-treatment, visual effect 2RT, visual effect 2RT retreatment. Re-treatment groups were lasered on days 0 and 21; single laser groups were only lasered on day 21. All rats were euthanized at day 28 and eyes were then dissected and processed for immunohistochemistry. For re-treatment, the laser was targeted at precisely the same locations on both delivery occasions. Analytical endpoints included monitoring of retinal vascular integrity overlying lesions, investigation into any potential choroidal neovascularization, assessment of the RPE, quantification of collateral injury to photoreceptors or other neuronal classes, and delineation of glial reactivity.
   Results: Repeat laser administration to rats caused ostensibly identical retinal-RPE-choroid responses to those obtained in age-matched rats that received only a single application. Specifically, 7 days after treatment, RPE cells were re-populating lesion sites. No obvious consistent differences were evident between the single and repeat laser groups. Moreover, repeat laser caused no (measurable) additive injury to photoreceptors or other retinal neuronal classes from single laser treatment. In re-lasered animals, there was no increase in microglial activity overlying and adjacent to lesion sites relative to single lasered rats. Finally, there was no evidence of choroidal neovascularization after repeat laser treatment.
   Conclusions: The overall results provide a measure of confidence that re-treatment of patients with 2RT should not provide any additional risk of developing visual scotomas, choroidal neovascularizations, or inflammatory events. Indeed, the collated results indicate that the metabolic and structural disruption to the RPE-retina caused by short pulse duration laser treatment is resolved within a short time frame such that re-treatment elicits a phenotype indistinguishable from single treatment. (C) 2016 Wiley Periodicals, Inc.
C1 [Chidlow, Glyn; Plunkett, Malcolm; Casson, Robert J.; Wood, John P. M.] Hanson Inst, Ctr Neurol, Ophthalm Res Labs, Frome Rd, Adelaide, SA 5000, Australia.
   [Chidlow, Glyn; Casson, Robert J.; Wood, John P. M.] Univ Adelaide, Discipline Ophthalmol & Visual Sci, Frome Rd, Adelaide, SA 5005, Australia.
C3 Hanson Institute; University of Adelaide
RP Chidlow, G (通讯作者)，Hanson Inst, Ctr Neurol, Ophthalm Res Labs, Frome Rd, Adelaide, SA 5000, Australia.
EM glyn.chidlow@health.sa.gov.au
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NR 43
TC 6
Z9 6
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0196-8092
EI 1096-9101
J9 LASER SURG MED
JI Lasers Surg. Med.
PD AUG
PY 2016
VL 48
IS 6
BP 602
EP 615
DI 10.1002/lsm.22506
PG 14
WC Dermatology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Dermatology; Surgery
GA DW0YP
UT WOS:000383369800006
PM 27320177
DA 2022-11-30
ER

PT J
AU Cho, H
   Shah, CP
   Weber, M
   Heier, JS
AF Cho, Hyung
   Shah, Chirag P.
   Weber, Marissa
   Heier, Jeffrey S.
TI Aflibercept for exudative AMD with persistent fluid on ranibizumab
   and/or bevacizumab
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Retina; Drugs; Macula; Neovascularisation; Treatment Medical
ID MACULAR DEGENERATION; VEGF-TRAP; TACHYPHYLAXIS; VERTEPORFIN; EYE
AB Objective
   To investigate the effect of aflibercept 2.0mg in cases resistant to ranibizumab 0.5mg and/or bevacizumab 1.25mg treatment.
   Purpose
   To evaluate the anatomic and visual effect of intravitreal aflibercept 2.0mg in cases of exudative age-related macular degeneration (AMD) with persistent fluid on optical coherence tomography (OCT) despite regular ranibizumab 0.5mg and/or bevacizumab 1.25mg treatment at 1 and 6months.
   Methods
   Retrospective review at Ophthalmic Consultants of Boston, Boston, Massachusetts, USA of exudative AMD cases with persistent fluid on regular ranibizumab 0.5mg and/or bevacizumab 1.25mg treatment switched to intravitreal aflibercept 2.0mg treatment and followed for 6months. Tabulated data included details of prior treatments, best available visual acuity, central subfoveal thickness on registered spectral domain OCT before and after aflibercept injection centred on the anatomic fovea and macular description before and after aflibercept injection.
   Results
   A total of 353 eyes with exudative AMD were switched to aflibercept during the study period. Of these, 28 eyes in 28 patients had persistent fluid after an average of 20 regular ranibizumab/bevacizumab injections (range 7-37). At 1month, 89% (25 eyes) showed anatomic improvement and 18% (five eyes) were dry after a single aflibercept injection. Central subfoveal thickness improved from 295 to 272 microns (p<0.001) after one aflibercept injection. After an average of 4.4 aflibercept injections (range 3-6) over 6months, the central subfoveal thickness remained improved (274 microns, p=0.008); 64% (18 eyes) showed anatomic improvement and a quarter of eyes (25%, seven eyes) were dry. Visual acuity did not improve at 1month (logarithm of minimum angle of resolution (logMAR) 0.54, Snellen 20/69, p=0.64) or 6months (logMAR 0.57, Snellen 20/76, p=0.49). Treatment was well tolerated with no adverse events reported.
   Conclusions
   A significant proportion of exudative AMD cases with persistent fluid on OCT despite regular ranibizumab 0.5mg and/or bevacizumab 1.25mg treatment respond anatomically to aflibercept 2.0mg. Visual acuity did not improve. Aflibercept may be beneficial anatomically in cases of exudative AMD treated with persistent fluid on ranibizumab and/or bevacizumab.
C1 [Cho, Hyung; Shah, Chirag P.; Weber, Marissa; Heier, Jeffrey S.] Ophthalm Consultants Boston, Dept Retina, Boston, MA 02114 USA.
C3 Ophthalmic Consultants of Boston
RP Heier, JS (通讯作者)，Ophthalm Consultants Boston, Dept Retina, 50 Staniford St,Suite 600, Boston, MA 02114 USA.
EM jsheier@eyeboston.com
FU Alcon; Alimera; Allergan; Fovea; Genentech; Genzyme; Partners; Neovista;
   Novartis; Ophthotech; Regeneron; GlaxoSmithKline; Notal Vision; Paloma
FX HC, MWnone; CPS-Sub-investigator on studies with the following sponsors:
   Alcon, Alimera, Allergan, Fovea, Genentech, Genzyme, Partners, Neovista,
   Novartis, Ophthotech, Regeneron; JSH-Consultancy: Acucela, Aerpio,
   Allergan, Bausch & Lomb, Bayer, Endo Optiks, Fovea, Genentech, Genzyme,
   GlaxoSmithKline, Kanghong, Notal Vision, Oraya, Paloma, QLT, Regeneron,
   Sequenom; Research Grant: Alcon, Alimera, Allergan, Fovea, Genentech,
   Genzyme, GlaxoSmithKline, Neovista, Notal Vision, Novartis, Ophthotech,
   Paloma, Regeneron.
CR Barbazetto I., 2012, AM SOC RET SPEC ANN
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NR 26
TC 117
Z9 120
U1 0
U2 15
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD AUG
PY 2013
VL 97
IS 8
BP 1032
EP 1035
DI 10.1136/bjophthalmol-2013-303344
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 186JI
UT WOS:000322039400019
PM 23766432
DA 2022-11-30
ER

PT J
AU Larsson, SC
   Burgess, S
AF Larsson, Susanna C.
   Burgess, Stephen
TI Appraising the causal role of smoking in multiple diseases: A systematic
   review and meta-analysis of Mendelian randomization studies
SO EBIOMEDICINE
LA English
DT Review
DE Cancer; Cardiovascular disease; Chronic diseases; Lifestyle factors;
   Mendelian randomization; Smoking
ID LIFE-STYLE FACTORS; CIGARETTE-SMOKING; ALZHEIMERS-DISEASE; TOBACCO
   SMOKING; RISK; INFLAMMATION; CATARACT
AB Background The causal association between cigarette smoking and several diseases remains equivocal. The purpose of this study was to appraise the causal role of smoking in a wide range of diseases by summarizing the evidence from Mendelian randomization (MR) studies. Methods MR studies on genetic liability to smoking initiation or lifetime smoking (composite of smoking initiation, heaviness, duration, and cessation) in relation to circulatory system, digestive system, nervous system, musculoskel-etal system, endocrine, metabolic, and eye diseases, and neoplasms published until February 15, 2022, were identi-fied in PubMed. De novo MR analyses were performed using summary statistics data from genome-wide association studies. Meta-analysis was applied to combine study-specific estimates. Findings Meta-analyses of findings of 29 published MR studies and 123 de novo MR analyses of 57 distinct primary outcomes showed that genetic liability to smoking (smoking initiation or lifetime smoking) was associated with increased risk of 13 circulatory system diseases, several digestive system diseases (including diverticular, gallstone, gastroesophageal reflux, and Crohn's disease, acute pancreatitis, and periodontitis), epilepsy, certain musculoskele-tal system diseases (including fracture, osteoarthritis, and rheumatoid arthritis), endocrine (polycystic ovary syn-drome), metabolic (type 2 diabetes) and eye diseases (including age-related macular degeneration and senile cataract) as well as cancers of the lung, head and neck, esophagus, pancreas, bladder, kidney, cervix, and ovaries, and myeloid leukemia. Smoking liability was associated with decreased risk of Parkinson's disease and prostate cancer. Interpretation This study found robust evidence that cigarette smoking causes a wide range of diseases. Funding This work was supported by research grants from the Swedish Cancer Society (Cancerfonden), the Swedish Heart Lung Foundation (Hjaeurort-Lungfonden, 20210351), the Swedish Research Council for Health, Working Life and Welfare (Forte, 2018-00123), and the Swedish Research Council (Vetenskapsra?det, 2019-00977). Stephen Burgess is supported by Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623/Z/ 16/Z) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. Copyright (C) 2022 The Author(s). Published by Elsevier B.V.
C1 [Larsson, Susanna C.] Uppsala Univ, Dept Surg Sci, Unit Med Epidemiol, Uppsala, Sweden.
   [Larsson, Susanna C.] Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden.
   [Burgess, Stephen] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, Cambs, England.
   [Burgess, Stephen] Univ Cambridge, MRC Biostat Unit, Cambridge, Cambs, England.
C3 Uppsala University; Karolinska Institutet; University of Cambridge; MRC
   Biostatistics Unit; University of Cambridge
RP Larsson, SC (通讯作者)，Uppsala Univ, Dept Surg Sci, Unit Med Epidemiol, Uppsala, Sweden.
EM susanna.larsson@surgsci.uu.se
OI Larsson, Susanna/0000-0003-0118-0341; Burgess,
   Stephen/0000-0001-5365-8760
FU Swedish Cancer Society (Cancerfonden); Swedish Heart Lung Foundation
   [204623/Z/16/Z]; Swedish Research Council for Health, Working Life and
   Welfare [20210351]; Swedish Research Council for Health, Working Life
   and Welfare [2019-00977]; Swedish Research Council [2018-00123];
   Wellcome Trust; Royal Society [2019-00977]; National Institute for
   Health Research Cambridge Biomedical Research Centre [204623/Z/16/Z];
   Sir Henry Dale Fellowship;  [BRC-1215-20014]
FX This work was supported by research grants from the Swedish Cancer
   Society (Cancerfonden) , the Swedish Heart Lung Foundation
   (Hjart-Lungfonden, 20210351) , the Swedish Research Council for Health,
   Working Life and Welfare (Forte, 2018-00123) , and the Swedish Research
   Council (Vetenskapsra det, 2019-00977) . Stephen Burgess is supported by
   Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the
   Royal Society (204623/Z/16/Z) and the National Institute for Health
   Research Cambridge Biomedical Research Centre (BRC-1215-20014) . The
   views expressed are those of the authors and not necessarily those of
   the National Institute for Health Research or the Department of Health
   and Social Care.
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NR 74
TC 2
Z9 2
U1 7
U2 7
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD AUG
PY 2022
VL 82
AR 104154
DI 10.1016/j.ebiom.2022.104154
PG 11
WC Medicine, General & Internal; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Research & Experimental Medicine
GA 3E1NG
UT WOS:000829756300004
PM 35816897
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Saldanha, IJ
   Lindsley, K
   Do, DV
   Chuck, RS
   Meyerle, C
   Jones, LS
   Coleman, AL
   Jampel, HD
   Dickersin, K
   Virgili, G
AF Saldanha, Ian J.
   Lindsley, Kristina
   Do, Diana V.
   Chuck, Roy S.
   Meyerle, Catherine
   Jones, Leslie S.
   Coleman, Anne L.
   Jampel, Henry D.
   Dickersin, Kay
   Virgili, Gianni
TI Comparison of Clinical Trial and Systematic Review Outcomes for the 4
   Most Prevalent Eye Diseases
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID VISUAL FUNCTION QUESTIONNAIRE; RANDOMIZED CONTROLLED-TRIALS;
   PATIENT-REPORTED OUTCOMES; SETS; GLAUCOMA; RESPONSIVENESS; CONSENSUS;
   DELPHI; ACUITY
AB IMPORTANCE Suboptimal overlap in outcomes reported in clinical trials and systematic reviews compromises efforts to compare and summarize results across these studies.
   OBJECTIVES To examine the most frequent outcomes used in trials and reviews of the 4 most prevalent eye diseases (age-related macular degeneration [AMD], cataract, diabetic retinopathy [DR], and glaucoma) and the overlap between outcomes in the reviews and the trials included in the reviews.
   DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study examined all Cochrane reviews that addressed AMD, cataract, DR, and glaucoma; were published as of July 20, 2016; and included at least 1 trial and the trials included in the reviews. For each disease, a pair of clinical experts independently classified all outcomes and resolved discrepancies. Outcomes (outcome domains) were then compared separately for each disease.
   MAIN OUTCOMES AND MEASURES Proportion of review outcomes also reported in trials and vice versa.
   RESULTS This study included 56 reviews that comprised 414 trials. Although the median number of outcomes per trial and per review was the same (n = 5) for each disease, the trials included a greater number of outcomes overall than did the reviews, ranging from 2.9 times greater (89 vs 30 outcomes for glaucoma) to 4.9 times greater (107 vs 22 outcomes for AMD). Most review outcomes, ranging from 14 of 19 outcomes (73.7%) (for DR) to 27 of 29 outcomes (93.1%) (for cataract), were also reported in the trials. For trial outcomes, however, the proportion also named in reviews was low, ranging from 19 of 107 outcomes (17.8%) (for AMD) to 24 of 89 outcomes (27.0%) (for glaucoma). Only 1 outcome (visual acuity) was consistently reported in greater than half the trials and greater than half the reviews.
   CONCLUSIONS AND RELEVANCE Although most review outcomes were reported in the trials, most trial outcomes were not reported in the reviews. The current analysis focused on outcome domains, which might underestimate the problem of inconsistent outcomes. Other important elements of an outcome (ie, specific measurement, specific metric, method of aggregation, and time points) might have differed even though the domains overlapped. Inconsistency in trial outcomesmay impede research synthesis and indicates the need for disease-specific core outcome sets in ophthalmology.
C1 [Saldanha, Ian J.; Lindsley, Kristina; Dickersin, Kay] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Room E6035, Baltimore, MD 21205 USA.
   [Do, Diana V.] Stanford Univ, Sch Med, Byers Eye Inst, Palo Alto, CA 94304 USA.
   [Chuck, Roy S.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Ophthalmol & Visual Sci, Bronx, NY 10467 USA.
   [Meyerle, Catherine; Jampel, Henry D.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
   [Jones, Leslie S.] Howard Univ Hosp, Dept Ophthalmol, Washington, DC USA.
   [Coleman, Anne L.] Univ Calif Los Angeles, David Geffen Sch Med, Frank & Ray Stark Fdn, Los Angeles, CA 90095 USA.
   [Virgili, Gianni] Univ Florence, Careggi Hosp, Dept Translat Surg & Med, Eye Clin, Florence, Italy.
C3 Johns Hopkins University; Johns Hopkins Bloomberg School of Public
   Health; Stanford University; Montefiore Medical Center; Yeshiva
   University; Albert Einstein College of Medicine; Johns Hopkins
   University; Johns Hopkins Medicine; Howard University; University of
   California System; University of California Los Angeles; University of
   California Los Angeles Medical Center; David Geffen School of Medicine
   at UCLA; University of Florence; Azienda Ospedaliero Universitaria
   Careggi
RP Saldanha, IJ (通讯作者)，Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Room E6035, Baltimore, MD 21205 USA.
EM isaldan1@jhmi.edu
RI Virgili, Gianni/P-6607-2014
OI Virgili, Gianni/0000-0002-9960-2989
FU National Institutes of Health [EY020140]; Cochrane Eyes and Vision
   [EY020522]; NATIONAL EYE INSTITUTE [U01EY020522] Funding Source: NIH
   RePORTER
FX This study was funded by grant EY020140 from the National Institutes of
   Health and grant EY020522 from Cochrane Eyes and Vision (Dr Dickersin).
CR Benstoem C, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0122204
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NR 37
TC 19
Z9 20
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD SEP
PY 2017
VL 135
IS 9
BP 933
EP 940
DI 10.1001/jamaophthalmol.2017.2583
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FG8HA
UT WOS:000410669300013
PM 28772305
OA Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Kutty, RK
   Samuel, W
   Boyce, K
   Cherukuri, A
   Duncan, T
   Jaworski, C
   Nagineni, CN
   Redmond, TM
AF Kutty, R. Krishnan
   Samuel, William
   Boyce, Kaifa
   Cherukuri, Aswini
   Duncan, Todd
   Jaworski, Cynthia
   Nagineni, Chandrasekharam N.
   Redmond, T. Michael
TI Proinflammatory cytokines decrease the expression of genes critical for
   RPE function
SO MOLECULAR VISION
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; MESENCHYMAL
   TRANSITION; E-CADHERIN; IN-VITRO; OXIDATIVE STRESS; INTERFERON-GAMMA;
   VISUAL CYCLE; CELL-LINE; ARPE-19
AB Purpose: Proinflammatory cytokines interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) secreted by infiltrating lymphocytes or macrophages may play a role in triggering RPE dysfunction associated with age-related macular degeneration (AMD). Binding of these proinflammatory cytokines to their specific receptors residing on the RPE cell surface can activate signaling pathways that, in turn, may dysregulate cellular gene expression. The purpose of the present study was to investigate whether IFN-gamma, TNF-alpha, and IL-1 beta have an adverse effect on the expression of genes essential for RPE function, employing the RPE cell line ARPE-19 as a model system.
   Methods: ARPE-19 cells were cultured for 3-4 months until they exhibited epithelial morphology and expressed mRNAs for visual cycle genes. The differentiated cells were treated with IFN-gamma, TNF-alpha, and/or IL-1 beta, and gene expression was analyzed with real-time PCR analysis. Western immunoblotting was employed for the detection of proteins.
   Results: Proinflammatory cytokines (IFN-gamma + TNF-alpha + IL-1 beta) greatly increased the expression of chemokines and cytokines in cultured ARPE-19 cells that exhibited RPE characteristics. However, this response was accompanied by markedly decreased expression of genes important for RPE function, such as CDH1, RPE65, RDH5, RDH10, TYR, and MERTK. This was associated with decreased expression of the genes MITF, TRPM1, and TRPM3, as well as microRNAs miR-204 and miR-211, which are known to regulate RPE-specific gene expression. The decreased expression of the epithelial marker gene CDH1 was associated with increased expression of mesenchymal marker genes (CDH2, VIM, and CCND1) and epithelial-mesenchymal transition (EMT) promoting transcription factor genes (ZEB1 and SNAI1).
   Conclusions: RPE cells exposed to proinflammatory cytokines IFN-gamma, TNF-alpha, and IL-1 beta showed decreased expression of key genes involved in the visual cycle, epithelial morphology, and phagocytosis. This adverse effect of proinflammatory cytokines, which could be secreted by infiltrating lymphocytes or macrophages, on the expression of genes indispensable for RPE function may contribute to the RPE dysfunction implicated in AMD pathology.
C1 [Kutty, R. Krishnan; Samuel, William; Boyce, Kaifa; Cherukuri, Aswini; Duncan, Todd; Jaworski, Cynthia; Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, NIH, Bldg 6,Room 112,6 Ctr Dr,MSC 0608, Bethesda, MD 20892 USA.
   [Nagineni, Chandrasekharam N.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); National Institutes of Health (NIH) - USA; NIH National Cancer
   Institute (NCI)
RP Kutty, RK (通讯作者)，NEI, Lab Retinal Cell & Mol Biol, NIH, Bldg 6,Room 112,6 Ctr Dr,MSC 0608, Bethesda, MD 20892 USA.
EM kuttyk@nei.nih.gov
OI Redmond, T. Michael/0000-0002-1813-5291
FU Intramural Research Program, NIH, NEI [1ZIAEY000444-09]; NATIONAL EYE
   INSTITUTE [ZIAEY000444] Funding Source: NIH RePORTER
FX The authors thank Dr. C. Vijayasarathy (National Institute on Deafness
   and Other Communication Disorders) for his contribution and critical
   reading of the manuscript. This study was supported by the Intramural
   Research Program, NIH, NEI (1ZIAEY000444-09).
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NR 53
TC 32
Z9 33
U1 0
U2 4
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD OCT 8
PY 2016
VL 22
BP 1156
EP 1168
PG 13
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA EK4NQ
UT WOS:000393904200001
PM 27733811
DA 2022-11-30
ER

PT J
AU Ahmad, I
   Del Debbio, CB
   Das, AV
   Parameswaran, S
AF Ahmad, Iqbal
   Del Debbio, Carolina B.
   Das, Ani V.
   Parameswaran, Sowmya
TI Muller Glia: A Promising Target for Therapeutic Regeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL STEM CELLS/PROGENITORS; NEURAL REGENERATION; MAMMALIAN RETINA;
   GOLDFISH RETINA; MOLECULAR CHARACTERIZATION; CELL PROPERTIES; LET-7
   MICRORNA; ADULT GOLDFISH; CHICKEN RETINA; IN-VITRO
AB In the past 10 years, there has been a paradigm shift in our understanding of brain development and approaches to treat degenerative diseases, including those that affect the retina. The latest knowledge includes (1) the discovery that the adult brain harbors proliferating progenitors and that neurons are born throughout life, particularly in the subventricular zone (SVZ) of the lateral ventricle and the subgranular layer (SGL) of the dentate gyrus of the hippocampus(1) and (2) the observation that glia perform dual functions, providing homeostatic support and serving as the source of stem cells in the embryonic brain and the adult SVZ and SGL.(2) In contrast to the SVZ and SGL, active neurogenesis has not been detected in adult mammalian retina. However, neurogenic changes have been observed in injured retina, and the source of injury-induced neurogenesis is traced to Muller glia, the sole glial cells generated by multipotential retinal progenitors. Recent evidence that a subset of Muller glia possesses an evolutionarily conserved stem cell potential has posited these cells as a viable target for replacing degenerating neurons in diseases such as age-related macular degeneration, retinitis pigmentosa, and glaucoma, where vision loss is due to the degeneration of specific types of neurons. This approach has the potential to effectively address significant barriers, such as the lack of a renewable source of cells that are nonimmunogenic and nonteratogenic, which currently makes ex vivo cell therapy approach impractical.
   This review describes the recent progress made in our understanding of the stem cell properties and regenerative potential of Muller glia and includes a discussion of (1) the development of Muller glia; (2) the neurogenic potential of Muller glia across species; (3) the characterization of Muller glia as stem cells; (4) the facile activation of Muller glia; and (5) the molecular mechanisms underlying the stemness (i.e., stem-like properties) of Muller glia. This information is critical in making potential therapeutic approaches effective, efficient, predictable, and safe. This review does not include the homeostatic functions of Muller glia; readers are referred to an excellent review on the topic by Bringmann et al.(3)
C1 [Ahmad, Iqbal; Del Debbio, Carolina B.; Das, Ani V.; Parameswaran, Sowmya] Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, Omaha, NE 68918 USA.
C3 University of Nebraska System; University of Nebraska Medical Center
RP Ahmad, I (通讯作者)，Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, Durham Res Ctr 1,98-5840 Nebraska Med Ctr, Omaha, NE 68918 USA.
EM iahmad@unmc.edu
RI Sowmya, Parameswaran/GZK-8635-2022
FU Lincy Foundation
FX Supported by the Lincy Foundation.
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NR 59
TC 41
Z9 44
U1 0
U2 16
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2011
VL 52
IS 8
BP 5758
EP 5764
DI 10.1167/iovs.11-7308
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800QC
UT WOS:000293377400096
PM 21803967
DA 2022-11-30
ER

PT J
AU Kothapalli, KSD
   Anthony, JC
   Pan, BS
   Hsieh, AT
   Nathanielsz, PW
   Brenna, JT
AF Kothapalli, Kumar S. D.
   Anthony, Joshua C.
   Pan, Bruce S.
   Hsieh, Andrea T.
   Nathanielsz, Peter W.
   Brenna, J. Thomas
TI Differential Cerebral Cortex Transcriptomes of Baboon Neonates Consuming
   Moderate and High Docosahexaenoic Acid Formulas
SO PLOS ONE
LA English
DT Article
ID POLYUNSATURATED FATTY-ACIDS; KERATAN SULFATE PROTEOGLYCAN; GLYCINE
   N-ACYLTRANSFERASE; SORSBYS FUNDUS DYSTROPHY; ALPHA CONVERTING-ENZYME;
   BREAST-MILK COMPOSITION; CENTRAL-NERVOUS-SYSTEM; BRAIN GENE-EXPRESSION;
   ANION CHANNEL VDAC; PROTEIN-KINASE-C
AB Background. Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6) are the major long chain polyunsaturated fatty acids (LCPUFA) of the central nervous system (CNS). These nutrients are present in most infant formulas at modest levels, intended to support visual and neural development. There are no investigations in primates of the biological consequences of dietary DHA at levels above those present in formulas but within normal breastmilk levels. Methods and Findings. Twelve baboons were divided into three formula groups: Control, with no DHA-ARA; "L", LCPUFA, with 0.33% DHA-0.67% ARA; "L3", LCPUFA, with 1.00% DHA-0.67% ARA. All the samples are from the precentral gyrus of cerebral cortex brain regions. At 12 weeks of age, changes in gene expression were detected in 1,108 of 54,000 probe sets (2.05%), with most showing < 2-fold change. Gene ontology analysis assigns them to diverse biological functions, notably lipid metabolism and transport, G-protein and signal transduction, development, visual perception, cytoskeleton, peptidases, stress response, transcription regulation, and 400 transcripts having no defined function. PLA2G6, a phospholipase recently associated with infantile neuroaxonal dystrophy, was downregulated in both LCPUFA groups. ELOVL5, a PUFA elongase, was the only LCPUFA biosynthetic enzyme that was differentially expressed. Mitochondrial fatty acid carrier, CPT2, was among several genes associated with mitochondrial fatty acid oxidation to be downregulated by high DHA, while the mitochondrial proton carrier, UCP2, was upregulated. TIMM8A, also known as deafness/dystonia peptide 1, was among several differentially expressed neural development genes. LUM and TIMP3, associated with corneal structure and age-related macular degeneration, respectively, were among visual perception genes influenced by LCPUFA. TIA1, a silencer of COX2 gene translation, is upregulated by high DHA. Ingenuity pathway analysis identified a highly significant nervous system network, with epidermal growth factor receptor (EGFR) as the outstanding interaction partner. Conclusions. These data indicate that LCPUFA concentrations within the normal range of human breastmilk induce global changes in gene expression across a wide array of processes, in addition to changes in visual and neural function normally associated with formula LCPUFA.
C1 [Kothapalli, Kumar S. D.; Pan, Bruce S.; Hsieh, Andrea T.; Brenna, J. Thomas] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
   [Anthony, Joshua C.] Mead Johnson & Co, Evansville, IN USA.
   [Nathanielsz, Peter W.] Univ Texas Hlth Sci Ctr San Antonio, Ctr Pregnancy & Newborn Res, San Antonio, TX 78229 USA.
C3 Cornell University; University of Texas System; University of Texas
   Health San Antonio
RP Brenna, JT (通讯作者)，Cornell Univ, Div Nutr Sci, Savage Hall, Ithaca, NY 14853 USA.
EM jtb4@cornell.edu
OI Nathanielsz, Peter/0000-0001-8410-6280; Brenna, James
   Thomas/0000-0001-9494-4245
FU Mead Johnson and Company, Evansville; NIH [NIH Training Grant DK07158];
   EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN
   DEVELOPMENT [P01HD021350] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [T32DK007158]
   Funding Source: NIH RePORTER
FX Funding: Mead Johnson and Company, Evansville, IN. BSP acknowledges
   support from NIH Training Grant DK07158.
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NR 188
TC 43
Z9 45
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 11
PY 2007
VL 2
IS 4
AR e370
DI 10.1371/journal.pone.0000370
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA V10DT
UT WOS:000207445400010
PM 17426818
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Liang, CS
   Wang, N
AF Liang, Changsen
   Wang, Ning
TI Subretinal Drusenoid Deposits and Lower Serum High-Density Lipoprotein
   Cholesterol Levels Possess Latent Relation to Cardiovascular Disease and
   Can Be a Feasible Predictor
SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE
LA English
DT Article
ID MACULAR DEGENERATION
AB Objective. To ascertain whether lipid-related subretinal drusenoid deposits (SDD) are correlated with coexisting cardiovascular disease (CVD), as well as to reveal latent serum markers of CVD. Methods. Patients older than 50 years and plagued by age-related macular degeneration (AMD) were included. Subjects with other retinal degenerations and vascular diseases, any recent treatment at other medical care institutions, and any previous oculopathy or ophthalmic surgery were excluded. All subjects were examined to ascertain whether they possess SDD, to analyze serum cholesterols, including low-density lipoprotein cholesterol (LDL), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and total cholesterol (TC). Subjects were divided into SDD and non-SDD groups and further divided into subgroups by assessment of pump defect, valve defect, and carotid defect. Finally, logistic model trees and random forest algorithm analysis were performed. Results. A total of 85 AMD patients including 43 with and 42 without SDD were involved. The 42 AMD (97.67%, 42/43) patients with SDD showed CVD, including 3 subjects presenting valve defect, 3 subjects presenting carotid defect, 8 subjects presenting pump defect, 14 subjects presenting both pump and valve defects, and 14 subjects presenting pump, valve, and carotid defects. By contrast, 5 AMD (11.90%, 5/42) patients without SDD showed CVD. Cholesterol level of SDD subjects presented significant higher TC (5.66 +/- 1.01 vs. 5.58 +/- 0.72, p = 0.032, Wilcoxon test) and lower HDL cholesterol (61 +/- 17 vs. 70 +/- 21, p = 0.031, Wilcoxon test) than that of non-SDD. The cases with HDL < 62 mg/dL were significantly related to CVD (p = 0.013, Wilcoxon test), and the cases with HDL < 40 mg/dL were not (p = 0.659, Wilcoxon test). Through machine learning based on the image from color fundus photography, the accuracy of predicting CVD was 95%. Conclusions. The presence of SDD of AMD and lower serum HDL cholesterol level can predict certain CVD for AMD patients. The machine learning based on the SDD image and serum HDL cholesterol may open new avenue for the detection of CVD as a noninvasive approach.
C1 [Liang, Changsen] Jinan Seventh Peoples Hosp, Dept Ophthalmol, Jinan 250132, Peoples R China.
   [Wang, Ning] Jinan Seventh Peoples Hosp, Dept Cardiovascularol, Jinan 250132, Peoples R China.
RP Wang, N (通讯作者)，Jinan Seventh Peoples Hosp, Dept Cardiovascularol, Jinan 250132, Peoples R China.
EM senlvning@163.com; ningowdb835713@163.com
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NR 25
TC 0
Z9 0
U1 1
U2 1
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1748-670X
EI 1748-6718
J9 COMPUT MATH METHOD M
JI Comput. Math. Method Med.
PD JUL 1
PY 2022
VL 2022
AR 3135100
DI 10.1155/2022/3135100
PG 6
WC Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Mathematical & Computational Biology
GA 3A7VY
UT WOS:000827464600015
PM 35813439
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Lennikov, A
   Mukwaya, A
   Saddala, MS
   Huang, H
AF Lennikov, Anton
   Mukwaya, Anthony
   Saddala, Madhu Sudhana
   Huang, Hu
TI Deficiency of C-X-C chemokine receptor type 5 (CXCR5) gene causes
   dysfunction of retinal pigment epithelium cells
SO LABORATORY INVESTIGATION
LA English
DT Article
ID PROTEIN; ACTIVATION; EXPRESSION; CULTURE
AB Homeostasis of the retinal pigment epithelium (RPE) is essential for the health and proper function of the retina. Regulation of RPE homeostasis is, however, largely unexplored, yet dysfunction of this process may lead to retinal degenerative diseases, including age-related macular degeneration (AMD). Here, we report that chemokine receptor CXCR5 regulates RPE homeostasis through PI3K/AKT signaling and by suppression of FOXO1 activation. We used primary RPE cells isolated from CXCR5-deficient mice and wild type controls, as well as ex vivo RPE-choroidal-scleral complexes (RCSC) to investigate the regulation of homeostasis. CXCR5 expression in mouse RPE cells was diminished by treatment with hydrogen peroxide. Lack of CXCR5 expression leads to an abnormal cellular shape, pigmentation, decreased expression of the RPE differentiation marker RPE65, an increase in the undifferentiated progenitor marker MITF, and compromised RPE barrier function, as well as compromised cell-to-cell interaction. An increase in epithelial-mesenchymal transition (EMT) markers (alpha SMA, N-cadherin, and vimentin) was noted in CXCR5-deficient RPE cells both in vitro and in age-progression specimens of CXCR5(-/-)mice (6, 12, 24-months old). Deregulated autophagy in CXCR5-deficient RPE cells was observed by decreased LC3B-II, increased p62, abnormal autophagosomes, and impaired lysosome enzymatic activity as shown by GFP-LC3-RFP reporter plasmid. Mechanistically, deficiency in CXCR5 resulted in the downregulation of PI3K and AKT signaling, but upregulation and nuclear localization of FOXO1. Additionally, inhibition of PI3K in RPE cells resulted in an increased expression of FOXO1. Inhibition of FOXO1, however, reverts the degradation of ZO-1 caused by CXCR5 deficiency. Collectively, these findings suggest that CXCR5 maintains PI3K/AKT signaling, which controls FOXO1 activation, thereby regulating the expression of genes involved in RPE EMT and autophagy deregulation.
   C-X-C chemokine receptor type 5 (CXCR5) regulates retinal pigment epithelium (RPE) homeostasis through PI3K/AKT signaling and by suppression of FOXO1 activation. CXCR5-deficency leads to decreased RPE differentiation, compromised barrier function, and increase in epithelial-mesenchymal transition markers (alpha SMA, N-cadherin, and vimentin) in CXCR5-deficient RPE cells in vitro and in CXCR5(-/-)mice.
C1 [Lennikov, Anton; Saddala, Madhu Sudhana; Huang, Hu] Univ Missouri, Sch Med, Dept Ophthalmol, Columbia, MO 65211 USA.
   [Mukwaya, Anthony] Linkoping Univ, Dept Ophthalmol, Inst Clin & Expt Med, Fac Hlth Sci, Linkoping, Sweden.
C3 University of Missouri System; University of Missouri Columbia;
   Linkoping University
RP Huang, H (通讯作者)，Univ Missouri, Sch Med, Dept Ophthalmol, Columbia, MO 65211 USA.
EM huangh1@missouri.edu
RI Mukwaya, Anthony/K-2335-2019
OI Mukwaya, Anthony/0000-0002-9645-8942
FU NIH [R01 EY027824]; Missouri University start-up funds
FX HH's research was supported by NIH grant R01 EY027824 and Missouri
   University start-up funds. The content is solely the responsibility of
   the authors and does not necessarily represent the official views of the
   National Institutes of Health.
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NR 36
TC 3
Z9 3
U1 0
U2 3
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2021
VL 101
IS 2
BP 228
EP 244
DI 10.1038/s41374-020-00491-4
EA SEP 2020
PG 17
WC Medicine, Research & Experimental; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pathology
GA PU0KC
UT WOS:000573751900002
PM 32994482
DA 2022-11-30
ER

PT J
AU Zhang, Y
   Zhao, L
   Wang, LJ
   Yang, XT
   Zhou, AY
   Wang, JM
AF Zhang, Yi
   Zhao, Lin
   Wang, Lijun
   Yang, Xiting
   Zhou, Aiyi
   Wang, Jianming
TI Placental growth factor promotes epithelial-mesenchymal transition-like
   changes in ARPE-19 cells under hypoxia
SO MOLECULAR VISION
LA English
DT Article
ID RETINAL ENDOTHELIAL-CELLS; MACULAR DEGENERATION; FACTOR CONTRIBUTES;
   FIBROSIS; VEGF; RANIBIZUMAB; ACTIVATION; PIGF; ANGIOGENESIS; MECHANISMS
AB Purpose: To investigate the role of placental growth factor (PGF) in the epithelial-mesenchymal transition (EMT) of ARPE-19 cells under hypoxia, and whether the NF-kappa B signaling pathway is involved in this process.
   Methods: ARPE-19 cells were treated in five groups: a control group, hypoxia group, PGF group, hypoxia+PGF group, and NF-kappa B-blocked group. A chemical hypoxia model was established in the ARPE-19 cells by adding CoCl2 to the culture medium. The morphological changes after treatment were observed. The proliferation rates were measured with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The migration abilities were measured with scratch assay. The EMT biomarkers were measured with quantitative real-time PCR (qRT-PCR), western blotting, and immunofluorescence. The relative protein expression of components of the NF-kappa B signaling pathway was measured with western blotting and immunofluorescence.
   Results: Cells treated with PGF under hypoxia exhibited morphological changes consistent with the transition from an epithelial to a mesenchymal phenotype. In the ARPE-19 cells, exogenous PGF under hypoxia increased the proliferation rate compared to the rate under hypoxia alone (p<0.05) and increased the migration rate (p<0.05). Treatment of hypoxiaexposed cells with PGF caused decreased expression of the epithelial biomarkers E-cadherin and ZO-1 (both p<0.05) and increased expression of the mesenchymal marker alpha-SMA (p<0.05) by enhancing the phosphorylation of NF-kappa B p65 of the total protein, promoting the translocation of p65 to the nucleus, and inducing the degradation of I kappa B-alpha (a negative regulator of the NF-kappa B pathway) in the ARPE-19 cells. Additionally, the effect of PGF-induced EMT in the ARPE-19 cells under hypoxia was counteracted with BAY 11-7082 (a selective NF-kappa B inhibitor).
   Conclusions: Exogenous PGF promotes EMT-like changes in ARPE-19 cells under hypoxia by activating the NF-kappa B signaling pathway. The study results suggest that PGF may play a role in scar formation in neovascular age-related macular degeneration (AMD) and that the inhibition of PGF may be a promising target for the prevention and treatment of AMD.
C1 [Zhang, Yi; Zhao, Lin; Wang, Lijun; Yang, Xiting; Zhou, Aiyi; Wang, Jianming] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Ophthalmol, Xian 71000, Shaanxi, Peoples R China.
C3 Xi'an Jiaotong University
RP Wang, JM (通讯作者)，Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Ophthalmol, Xian 71000, Shaanxi, Peoples R China.
EM sandy_chow@126.com; xajdwjm@163.com
FU Shaanxi Province [2017SF-266]
FX This study was supported by the key research and development project of
   Shaanxi Province (2017SF-266). The authors declare no competing
   financial interests. Dr. Jianming Wang (xajdwjm@163.com) and Dr. Aiyi
   Zhou (sandy_chow@126.com) are co-corresponding authors on this paper.
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NR 52
TC 11
Z9 12
U1 0
U2 7
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD APR 26
PY 2018
VL 24
BP 340
EP 352
PG 13
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA GF1FN
UT WOS:000431679100002
PM 29769799
DA 2022-11-30
ER

PT J
AU Cislo-Pakuluk, A
   Marycz, K
AF Cislo-Pakuluk, Anna
   Marycz, Krzysztof
TI A Promising Tool in Retina Regeneration: Current Perspectives and
   Challenges When Using Mesenchymal Progenitor Stem Cells in Veterinary
   and Human Ophthalmological Applications
SO STEM CELL REVIEWS AND REPORTS
LA English
DT Review
DE Human retinal diseases; Glaucoma neuroprotection; Stem cell therapy;
   Retinal vascular diseases retinal pigment epithelium regeneration
ID RAT MODEL; SUBRETINAL TRANSPLANTATION; DIFFERENTIATION; GLAUCOMA;
   NEUROPROTECTION; DEGENERATION; REPAIR
AB Visual impairment is a common ailment of the current world population, with more exposure to CCD screens and fluorescent lighting, approximately 285 billion people suffer from this deficiency and 13% of those are considered clinically blind. More common causes for visual impairment include age-related macular degeneration (AMD), glaucoma and diabetic retinopathy (Zhu et al. Molecular Medicine Reports, 2015; Kolb et al. 2007; MachaliA"ska et al. Current Eye Research, 34(9),748-760, 2009) among a few. As cases of retinal and optic nerve diseases rise, it is vital to find a treatment, which has led to investigation of the therapeutic potential of various stem cells types (Bull et al. Investigative Opthalmology & Visual Science, 50(9), 4244, 2009; Bull et al. Investigative Opthalmology & Visual Science, 49(8), 3449, 2008; Yu et al. Biochemical and Biophysical Research Communications, 344(4), 1071-1079, 2006; Na et al. Graefe's Archive for Clinical and Experimental Ophthalmology, 247(4), 503-514, 2008). In previous studies, some of the stem cell variants used include human Muller SCs and bone marrow derived SCs. Some of the regenerative potential characteristics of mesenchymal progenitor stem cells (MSCs) include their multilineage differentiation potential, their immunomodulatory effects, their high proliferative activity, they can be easily cultured in vitro, and finally their potential to synthesize and secrete membrane derived vesicles rich in growth factors, mRNA and miRNA which possibly aid in regulation of tissue damage regeneration. These facts alone, explain why MSCs are so widely used in clinical trials, 350 up to date (Switonski, Reproductive Biology, 14(1), 44-50, 2014). Animal studies have demonstrated that sub-retinal transplantation of MSCs delays retinal degeneration and preserves retinal function through trophic response (Inoue et al. Experimental Eye Research, 85(2), 234-241, 2007). Umbilical cord derived MSCs (UC/MSCs) have also been shown to contain neuroprotective features of ganglion cells in rat studies (Zwart et al. Experimental Neurology, 216(2), 439-448, 2009). This review aims to present current MSC therapies in practice, as well as their retinal regeneration potential in animal models, and their innovative prospects for treatment of human retinal diseases.
C1 [Cislo-Pakuluk, Anna] Vet Clin Trzebnicka, Kosciuszki 18, PL-55100 Trzebnica, Poland.
   [Marycz, Krzysztof] Wroclaw Univ Environm & Life Sci, Dept Expt Biol, CK Norwida 25, PL-50375 Wroclaw, Poland.
C3 Wroclaw University of Environmental & Life Sciences
RP Marycz, K (通讯作者)，Wroclaw Univ Environm & Life Sci, Dept Expt Biol, CK Norwida 25, PL-50375 Wroclaw, Poland.
EM krzysztof.marycz@upwr.edu.pl
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NR 43
TC 40
Z9 44
U1 0
U2 30
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 2629-3269
EI 2629-3277
J9 STEM CELL REV REP
JI Stem Cell Rev. Rep.
PD OCT
PY 2017
VL 13
IS 5
BP 598
EP 602
DI 10.1007/s12015-017-9750-4
PG 5
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA FH0IQ
UT WOS:000410823500004
PM 28643176
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Jones, MK
   Lu, B
   Saghizadeh, M
   Wang, SM
AF Jones, Melissa K.
   Lu, Bin
   Saghizadeh, Mehrnoosh
   Wang, Shaomei
TI Gene expression changes in the retina following subretinal injection of
   human neural progenitor cells into a rodent model for retinal
   degeneration
SO MOLECULAR VISION
LA English
DT Article
ID MICROARRAY EXPERIMENT MIAME; STEM-CELLS; MACULAR DEGENERATION;
   DIABETIC-RETINOPATHY; ALPHA-V-BETA-5 INTEGRIN; MINIMUM INFORMATION;
   PIGMENT-EPITHELIUM; DIFFERENTIAL GENE; OUTER SEGMENTS; POTENTIAL ROLE
AB Purpose: Retinal degenerative diseases (RDDs) affect millions of people and are the leading cause of vision loss. Although treatment options for RDDs are limited, stem and progenitor cell-based therapies have great potential to halt or slow the progression of vision loss. Our previous studies have shown that a single subretinal injection of human forebrain derived neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) retinal degenerate rat offers long-term preservation of photoreceptors and visual function. Furthermore, neural progenitor cells are currently in clinical trials for treating age-related macular degeneration; however, the molecular mechanisms of stem cell-based therapies are largely unknown. This is the first study to analyze gene expression changes in the retina of RCS rats following subretinal injection of hNPCs using high-throughput sequencing.
   Methods: RNA-seq data of retinas from RCS rats injected with hNPCs (RCShNPCs) were compared to sham surgery in RCS (RCSsham) and wild-type Long Evans (LEsham) rats. Differential gene expression patterns were determined with in silico analysis and confirmed with qRT-PCR. Function, biologic, cellular component, and pathway analyses were performed on differentially expressed genes and investigated with immunofluorescent staining experiments.
   Results: Analysis of the gene expression data sets identified 1,215 genes that were differentially expressed between RCSsham and LEsham samples. Additionally, 283 genes were differentially expressed between the RCShNPCs and RCSsham samples. Comparison of these two gene sets identified 68 genes with inverse expression (termed rescue genes), including Pdc, Rp1, and Cdc42ep5. Functional, biologic, and cellular component analyses indicate that the immune response is enhanced in RCSsham. Pathway analysis of the differential expression gene sets identified three affected pathways in RCShNPCs, which all play roles in phagocytosis signaling. Immunofluorescent staining detected the increased presence of macrophages and microglia in RCSsham retinas, which decreased in RCShNPCs retinas similar to the patterns detected in LEsham.
   Conclusions: The results from this study provide evidence of the gene expression changes that occur following treatment with hNPCs in the degenerating retina. This information can be used in future studies to potentially enhance or predict responses to hNPC and other stem cell therapies for retinal degenerative diseases.
C1 [Jones, Melissa K.; Lu, Bin; Saghizadeh, Mehrnoosh; Wang, Shaomei] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA.
   [Jones, Melissa K.; Lu, Bin; Saghizadeh, Mehrnoosh; Wang, Shaomei] Cedars Sinai Med Ctr, Board Governors Regenerat Med Inst, Eye Program, Los Angeles, CA 90048 USA.
   [Saghizadeh, Mehrnoosh; Wang, Shaomei] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
C3 Cedars Sinai Medical Center; Cedars Sinai Medical Center; University of
   California System; University of California Los Angeles; University of
   California Los Angeles Medical Center; David Geffen School of Medicine
   at UCLA
RP Wang, SM (通讯作者)，Cedars Sinai Med Ctr, Board Governors Regenerat Med Inst, 8700 Beverly Blvd, Los Angeles, CA 90048 USA.
EM shaomei.wang@cshs.org
FU NEI [R01EY020488]; California Institute for Regenerative Medicine
   [LSP1-08235]; Cedars-Sinai Medical Center Board of Governors
   Regenerative Medicine Institute; NATIONAL EYE INSTITUTE [R01EY020488]
   Funding Source: NIH RePORTER
FX The authors thank Lindsay Spurka and Dr. Vincent Funari from the
   Cedars-Sinai Genomics Core for support with the RNA-seq. The authors
   also acknowledge the laboratories of Dr. Clive Svendsen and Dr. Barry
   Stripp for assistance, and Lin Shen for technical support. This work was
   supported by funding from the NEI (R01EY020488), California Institute
   for Regenerative Medicine (LSP1-08235), and Cedars-Sinai Medical Center
   Board of Governors Regenerative Medicine Institute. A portion of this
   study was submitted for presentation at the 2016 Association for
   Research in Vision and Ophthalmology annual meeting in Seattle, WA.
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NR 109
TC 12
Z9 12
U1 0
U2 15
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD MAY 16
PY 2016
VL 22
BP 472
EP 490
PG 19
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA DM1YI
UT WOS:000376142400002
PM 27217715
DA 2022-11-30
ER

PT J
AU Bretillon, L
   Thuret, G
   Gregoire, S
   Acar, N
   Joffre, C
   Bron, AM
   Gain, P
   Creuzot-Garcher, CP
AF Bretillon, Lionel
   Thuret, Gilles
   Gregoire, Stephane
   Acar, Niyazi
   Joffre, Corinne
   Bron, Alain M.
   Gain, Philippe
   Creuzot-Garcher, Catherine P.
TI Lipid and fatty acid profile of the retina, retinal pigment
   epithelium/choroid, and the lacrimal gland, and associations with
   adipose tissue fatty acids in human subjects
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE lipid; nutrition; retina; retinal pigment epithelium; Bruch's membrane;
   lacrimal gland
ID AGE-RELATED MACULOPATHY; LIPOPROTEIN-LIKE PARTICLES; HUMAN BRUCHS
   MEMBRANE; BASAL LINEAR DEPOSIT; ROD OUTER SEGMENTS; DOCOSAHEXAENOIC
   ACID; MACULAR DEGENERATION; CHOLESTERYL ESTERS; OXIDATIVE STRESS;
   CELL-SURVIVAL
AB Accumulation of lipids within Bruch's membrane (BrM) and between BrM and retinal pigment epithelium (RPE) accounts for one of the biological changes associated with normal aging and may contribute to the development of age-related maculopathies. The origin of these lipids is still being actively investigated. The relative contribution of plasma lipids and lipids coming from the neural retina remains a matter of controversy. Low-density lipoproteins (LDLs) have been reported to significantly participate in the retina's lipid supply, after active remodeling within RPE. Meanwhile, RPE expresses the enzymatic machinery for synthesizing lipoprotein-like particles. The objective of this study was to establish associations between the fatty acid profile of the ocular structures and adipose tissue as a surrogate for the subjects' past dietary intake. Lipids and fatty acids were analyzed from the neural retina, retinal pigment epithelium (RPE)/choroid, the lacrimal gland, and adipose tissue, collected from 27 human donors (19 women, eight men) aged 59-95 years. DNA concentrations in the neural retina were positively associated with the concentrations in cholesteryl esters (CEs) from RPE/choroid and negatively associated with DHA concentrations in phospholipids (PLs) from RPE/choroid. DHA in orbital fat was positively associated with DHA in the lacrimal gland. No significant association was observed in the other ocular structures. Linoleic acid in orbital fat was positively associated with linoleic acid in the lacrimal gland, followed by the neural retina and CEs from RPE/choroid; it was slightly correlated with PLs from RPE/choroid. Other fatty acids that originate exclusively from the diet such as trans fatty acids were detected in orbital fat, the lacrimal gland, PLs, and CEs from RPE/choroid. DHA in the neural retina was poorly associated with its dietary intake, contrary to other fatty acids such as linoleic acid. Within this context, CEs may be important carriers of fatty acids entering the retina. Although epidemiological studies have reported the benefit of DHA in the prevention of age-related macular degeneration, the leading cause of blindness in Western countries, the relevance of supplementing patients with DHA is questioned. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Bretillon, Lionel; Gregoire, Stephane; Acar, Niyazi; Joffre, Corinne] INRA, FLAVIC, Eye & Nutr Res Grp, UMR1129, F-21065 Dijon, France.
   [Thuret, Gilles; Gain, Philippe] Fac Med, Dept Ophthalmol Biol Imaging & Engn Corneal Graft, St Etienne, France.
   [Bron, Alain M.; Creuzot-Garcher, Catherine P.] Univ Burgundy, Eye & Nutr Res Grp, UMR1129, FLAVIC, Dijon, France.
   [Bron, Alain M.; Creuzot-Garcher, Catherine P.] Univ Hosp, Dept Ophthalmol, Dijon, France.
C3 INRAE; Institut Agro; AgroSup Dijon; Universite de Bourgogne; Universite
   de Franche-Comte; Institut Agro; AgroSup Dijon; Universite de Bourgogne;
   CHU Dijon Bourgogne
RP Bretillon, L (通讯作者)，INRA, FLAVIC, Eye & Nutr Res Grp, UMR1129, 17 Rue Sully,BP 86510, F-21065 Dijon, France.
EM lionel.bretillon@dijon.inra.fr
RI wei, chi/H-5730-2011; Bron, Alain/AAP-8010-2020
OI Bron, Alain/0000-0002-7265-931X; JOFFRE, Corinne/0000-0001-8327-3554;
   Bretillon, Lionel/0000-0002-6957-100X
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   [No title captured]
NR 59
TC 75
Z9 75
U1 1
U2 14
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD DEC
PY 2008
VL 87
IS 6
BP 521
EP 528
DI 10.1016/j.exer.2008.08.010
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 385OQ
UT WOS:000261823900005
PM 18801361
DA 2022-11-30
ER

PT J
AU Yang, P
   Peairs, JJ
   Tano, R
   Zhang, NF
   Tyrell, J
   Jaffe, GJ
AF Yang, Ping
   Peairs, James J.
   Tano, Ryotaro
   Zhang, Nanfei
   Tyrell, Jillian
   Jaffe, Glenn J.
TI Caspase-8-mediated apoptosis in human RPE cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID NF-KAPPA-B; TRAIL-INDUCED APOPTOSIS; CHOROIDAL NEOVASCULAR MEMBRANES;
   ADENOVIRUS-MEDIATED TRANSFER; ENDOTHELIAL GROWTH-FACTOR; ALPHA-INDUCED
   APOPTOSIS; AGE-RELATED MACULOPATHY; CYTOCHROME-C RELEASE; PROLIFERATIVE
   VITREORETINOPATHY; EPITHELIAL-CELLS
AB PURPOSE. Tumor necrosis factor (TNF)-alpha is an important cytokine associated with age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). TNF-alpha activates the extrinsic apoptotic pathway. In many cells, nuclear transcription factor (NF)-kappa B upregulates antiapoptotic proteins and prevents TNF-alpha-mediated apoptosis. However, retinal pigment epithelial (RPE) cells are resistant to TNF-alpha-induced apoptosis, even after specific NF-kappa B blockade. Herein, the authors investigated the role of caspase-8 in RPE cell resistance to TNF-alpha-mediated cell death.
   METHODS. Caspase-8 mRNA and protein expression were measured in human RPE cells, human lens epithelial cells, human trabecular meshwork (TM) cells, human choroidal endothelial cells, human uveal melanoma cells (OCM-1, 92.1 and MKT-BR), T-98G, OVCAR-3, HCT116, and Jurkat cancer cells by real-time reverse transcription-polymerase chain reaction and Western blot, respectively. RPE cells were coinfected with adenovirus encoding caspase-8 and Cre. RPE and T-98G cells were infected with adenovirus encoding mutant inhibitory (I)-kappa B and then were treated with media alone or with TNF-alpha. Cell viability was determined by WST-1 assay, and apoptosis was evaluated with DNA fragmentation assay and M30 assay. Caspase-3, -7, -9 expression and Bid protein expression after caspase-8 overexpression were examined by Western blot.
   RESULTS. Human RPE cell caspase-8 mRNA and protein levels were low compared with levels in nonneoplastic ocular cells and cancer cells. Overexpression of caspase- 8 significantly decreased cell number, caused caspase-8 and caspase-3 activation, decreased full-length Bid, caspase-9, and caspase-7, and significantly increased DNA fragmentation and M30-positive RPE cells. Without TNF-alpha treatment, NF-kappa B blockade had no effect on caspase-8-mediated RPE cell death. In the presence of TNF-alpha, NF-kappa B blockade slightly but significantly enhanced caspase-8-mediated RPE cell death.
   CONCLUSIONS. RPE cell caspase-8 protein levels are low compared with levels for other cell types and may be regulated posttranscriptionally. Low caspase-8 levels may protect RPE cells from apoptosis normally and in diseases such as AMD and may promote the survival of abnormal cells in PVR. Introduction of caspase-8 into RPE cells may be a potential strategy to treat PVR.
C1 Duke Univ, Ctr Eye, Dept Ophthalmol, Durham, NC 27710 USA.
C3 Duke University
RP Jaffe, GJ (通讯作者)，Duke Univ, Ctr Eye, Dept Ophthalmol, Box 3802, Durham, NC 27710 USA.
EM jaffe001@mc.duke.edu
FU NEI NIH HHS [930EY05722, R01 EY9106] Funding Source: Medline; NATIONAL
   EYE INSTITUTE [R01EY009106] Funding Source: NIH RePORTER
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NR 53
TC 37
Z9 38
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2007
VL 48
IS 7
BP 3341
EP 3349
DI 10.1167/iovs.06-1340
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 187NT
UT WOS:000247855600050
PM 17591907
DA 2022-11-30
ER

PT J
AU Frohlich, SJ
AF Frohlich, SJ
TI Age-related macula degeneration and diabetic retinopathy - Differences
   in optic rehabilitation
SO KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE
LA English
DT Article
DE optic rehabilitation; age-related macular degeneration; diabetic
   retinopathy; magnifying devices; low vision
AB Background: Age-related macular degeneration (AMD) and diabetes mellitus are the major contributing causes of visual impairment in the industrial nations. This study shows how far visual acuity (VA) and magnification demand (MD) influence the selection of suitable low vision aids. Based on this information, differences regarding the spectrum of prescribed magnifying devices between both patient groups will be presented. Materials and Methods: Between January 2003 and October 2004, a total of 2500 patients was seen in our Low Vision Department. Among them were 1198 patients with AMD (48%) and 296 visually impaired patients because of diabetic ocular involvement (12%). In every patient, best corrected distance and near VA as well as the required MD were measured. Finally, matching of magnifying aids and discussing aspects of professional and social rehabilitation were the main parts of our interdisciplinary Low Vision Service. Results: In AMD patients, the average of best corrected distance VA at the better eye was 0.24, the best corrected near VA was 0.19. In diabetes patients, the average of best corrected distance VA at the better eye was 0.28, the best corrected near VA was 0.22. The required mean MD was 4.0 x (related to the reading of newspaper text) compared to 7.6 x in patients with AMD. In 94% of the visually impaired diabetes patients, optical magnifiers could be prescribed (e. g. magnifying eyeglasses, telescopes, monoculars, Galelean and Keplerian systems), whereas electronic devices were necessary in only 6%. In comparison, 14.8% of the patients with AMD had to be provided with electronic systems. Conclusions: In 94% of the visually impaired patients caused by diabetes, reading ability could be restored using optical low vision aids. In AMD patients, this could be achieved in only 85.2%. This fact can mainly be explained with the negative effect of absolute central scotomas on reading speed in AMD patients which leads, compared to diabetes patients, to elevated magnification factors. Therefore, the choice of certain magnifying devices depends not only on VA, but has mainly to be evaluated based on the individual MD.
C1 LMU, Augenklin, Ambulanz Vergrossernde Sehhilfen, D-80336 Munich, Germany.
C3 University of Hamburg; University Medical Center Hamburg-Eppendorf;
   University of Munich
RP Frohlich, SJ (通讯作者)，LMU, Augenklin, Ambulanz Vergrossernde Sehhilfen, Mathildenstr 8, D-80336 Munich, Germany.
EM Stephan.Froehlich@med.uni-muenchen.de
CR FROHLICH SJ, 2004, AUGENHEILKD, V25, P87
   FROHLICH SJ, 2004, EUR J OPHTHALMOL, V14, P179
   FROHLICH SJ, 2004, Z PRAKT AUGENHEILKD, V25, P333
   Grein H, 2002, OPHTHALMOLOGE, V99, P884, DOI 10.1007/s00347-002-0704-z
   Grein HJ, 2002, OPHTHALMOLOGE, V99, P794, DOI 10.1007/s00347-002-0703-0
NR 5
TC 6
Z9 6
U1 0
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0023-2165
J9 KLIN MONATSBL AUGENH
JI Klinische Monatsblat. Augenheilkunde
PD APR
PY 2005
VL 222
IS 4
BP 337
EP 341
DI 10.1055/s-2005-858089
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 923TV
UT WOS:000228933100008
PM 15844045
DA 2022-11-30
ER

PT J
AU Tsukahara, I
   Ninomiya, S
   Castellarin, A
   Yagi, F
   Sugino, IK
   Zarbin, MA
AF Tsukahara, I
   Ninomiya, S
   Castellarin, A
   Yagi, F
   Sugino, IK
   Zarbin, MA
TI Early attachment of uncultured retinal pigment epithelium from aged
   donors onto Bruch's membrane explants
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retinal pigment epithelium; Bruch's membrane; age-related macular
   degeneration; RPE transplantation
ID SUBFOVEAL NEOVASCULAR MEMBRANES; BLUE MOUNTAINS EYE; MACULAR
   DEGENERATION; CLINICOPATHOLOGICAL CORRELATION; CHOROIDAL
   NEOVASCULARIZATION; SURGICAL REMOVAL; SUBRETINAL SPACE; CELL
   TRANSPLANTATION; RPE ALLOGRAFTS; SUBMACULAR MEMBRANECTOMY
AB Retinal pigment epithelium (RPE) transplantation might replace cells lost as a consequence of choroidal neovascular membrane excision in patients with age-related macular degeneration (AMD). Autologous transplantation of RPE cells harvested from a peripheral biopsy may overcome problems of immune rejection. To study the feasibility of autologous RPE cell transplantation, the authors examined the attachment of freshly harvested RPE cells from aged donors onto Bruch's membrane explants, debrided to (1) remove or (2) preserve the RPE basement membrane. Human retinal pigment epithelial sheets were harvested from adult donor eyes (N = 12, mean age 79-00 +/- 9.40 years) and, following incubation in collagenase, were mechanically fragmented into micro aggregates, Microaggregates (approximately 120 000 cells) were seeded onto the paired explants (7 mm diameter) and incubated for 20 min, 1, 4, or 24 hr at 37degreesC. The percent coverage of the debrided surface by microaggregates was determined by sampling the center of the explants with scanning electron microscopy. RPE microaggregate attachment to Bruch's membrane was significantly greater at all time points analysed in samples with intact basement membrane versus those with an exposed inner collagenous layer. Coverage of debridements retaining intact RPE basement membrane was 1.83 +/- 1.10% at 20 min, 3.54 +/- 2.14 % at 1 hr, and 8.68 +/- 2.63 % at 4 hr. Coverage of debridements lacking basement membrane was 0.10 +/- 0.04% at 20 min, 0.39 +/- 0.25 % at I hr, and 0.63 +/- 0.42% at 4 hr. Based on their morphologic appearance, many cells were dying as early as 1 hr following seeding. To increase surface coverage, the authors seeded four times the above number of cells and incubated the specimens for 1 hr. Coverage on explants lacking RPE basement membrane showed no increase in the number of cells attached to the inner collagenous layer. There was a significant approximately three-fold increase in the number of cells attached in the presence of basement membrane. These results indicate that if RPE cells from aged human donors are used for transplantation, some modification of the Bruch's membrane surface or the cells must be considered for cell attachment and eventual cell survival. (C) 2002 Elsevier Science Ltd.
C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Ophthalmol, Newark, NJ 07103 USA.
C3 Rutgers State University New Brunswick; Rutgers State University Medical
   Center
RP Zarbin, MA (通讯作者)，Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Ophthalmol, Newark, NJ 07103 USA.
OI Zarbin, Marco/0000-0002-7811-7132
FU NEI NIH HHS [R01 EY 07950-07] Funding Source: Medline
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NR 83
TC 38
Z9 41
U1 0
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2002
VL 74
IS 2
BP 255
EP 266
DI 10.1006/exer.2001.1123
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 551AT
UT WOS:000175537800011
PM 11950236
DA 2022-11-30
ER

PT J
AU Singh, CSB
   Choi, KB
   Munro, L
   Wang, HY
   Pfeifer, CG
   Jefferies, WA
AF Singh, Chaahat S. B.
   Choi, Kyung Bok
   Munro, Lonna
   Wang, Hong Yue
   Pfeifer, Cheryl G.
   Jefferies, Wilfred A.
TI Reversing pathology in a preclinical model of Alzheimer's disease by
   hacking cerebrovascular neoangiogenesis with advanced cancer
   therapeutics
SO EBIOMEDICINE
LA English
DT Article
DE Alzheimer's disease (AD); Angiogenesis; Amyloid-beta(Ab); Axitinib;
   Blood-brain barrier (BBB); Cognitive restoration; Anti-angiogenic drug
   treatment; Tg2576 mouse model
ID CEREBRAL AMYLOID ANGIOPATHY; RENAL-CELL CARCINOMA; TG2576 MOUSE MODEL;
   A-BETA; VASCULAR DYSFUNCTION; AXITINIB; MEMORY; BRAIN; ANTIANGIOGENESIS;
   DEGENERATION
AB Background: Cognitive decline leading to dementia, accompanied by the accumulation of amyloid-beta (A beta) in neuritic plaques together with the appearance of neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein (tau), are previously noted hallmarks of Alzheimer's disease (AD). We previously discovered hypervascularity in brain specimens from AD patients and consistent with this observation, we demonstrated that overexpression of A beta drives cerebrovascular neoangiogenesis leading to hypervascularity and coincident tight-junction disruption and blood-brain barrier (BBB) leakiness in animal models of AD. We subsequently demonstrated that amyloid plaque burden and cerebrovascular pathogenesis subside when pro-angiogenic A beta levels are reduced. Based on these data, we propose a paradigm of AD etiology where, as a compensatory response to impaired cerebral blood flow (CBF), A beta triggers pathogenic cerebrovascular neoangiogenesis that underlies the conventional hallmarks of AD. Consequently, here we present evidence that repurposing anti-cancer drugs to modulate cerebrovascular neoangiogenesis, rather than directly targeting the amyloid cascade, may provide an effective treatment for AD and related vascular diseases of the brain.
   Methods: We explored whether the anti-cancer drug, Axitinib, a small molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR) can inhibit aberrant cerebrovascular neoangiogenic changes, reduce A beta deposits and reverse cognitive decline in an animal model of AD. One month post-treatment with Axitinib, we employed a battery of tests to assess cognition and memory in aged Tg2576 AD mice and used molecular analysis to demonstrate reduction of amyloid plaques, BBB leakage, hypervascularity and associated disease pathology.
   Findings: Targeting the pro-angiogenic pathway in AD using the cancer drug, Axitinib, dramatically reduced cerebrovascular neoangiogenesis, restored BBB integrity, resolved tight-junction pathogenesis, diminishes A beta depositions in plaques and effectively restores memory and cognitive performance in a preclinical mouse model of AD.
   Interpretation: Modulation of neoangiogenesis, in an analogous approach to those used to treat aberrant vascularization in cancer and also in the wet form of age-related macular degeneration (AMD), provides an alternative therapeutic strategy for intervention in AD that warrants clinical investigation. (C) 2021 Published by Elsevier B.V.
C1 [Singh, Chaahat S. B.; Choi, Kyung Bok; Munro, Lonna; Wang, Hong Yue; Pfeifer, Cheryl G.; Jefferies, Wilfred A.] Univ British Columbia, Dept Med Genet, 2350 Hlth Sci Mall, Vancouver, BC V6T 1Z4, Canada.
   [Singh, Chaahat S. B.; Choi, Kyung Bok; Munro, Lonna; Wang, Hong Yue; Pfeifer, Cheryl G.; Jefferies, Wilfred A.] Univ British Columbia, Michael Smith Labs, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada.
   [Singh, Chaahat S. B.; Choi, Kyung Bok; Munro, Lonna; Pfeifer, Cheryl G.; Jefferies, Wilfred A.] Univ British Columbia, Ctr Blood Res, 2350 Hlth Sci Mall, Vancouver, BC V6T 1Z4, Canada.
   [Singh, Chaahat S. B.; Choi, Kyung Bok; Munro, Lonna; Pfeifer, Cheryl G.; Jefferies, Wilfred A.] Univ British Columbia, Djavad Mowafaghian Ctr Brain Hlth, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada.
   [Choi, Kyung Bok; Munro, Lonna; Pfeifer, Cheryl G.; Jefferies, Wilfred A.] Univ British Columbia, Dept Microbiol & Immunol, 2350 Hlth Sci Mall, Vancouver, BC V6T 1Z4, Canada.
   [Choi, Kyung Bok; Munro, Lonna; Pfeifer, Cheryl G.; Jefferies, Wilfred A.] Univ British Columbia, Dept Zool, 6270 Univ Blvd, Vancouver, BC V6T 1Z4, Canada.
   [Singh, Chaahat S. B.; Choi, Kyung Bok; Munro, Lonna; Pfeifer, Cheryl G.; Jefferies, Wilfred A.] Vancouver Gen Hosp, Vancouver Prostate Ctr, 2660 Oak St, Vancouver, BC V6T 1Z4, Canada.
   [Jefferies, Wilfred A.] Univ British Columbia, Gordon & Leslie Diamond Hlth Care Ctr, Dept Urol Sci, Level 6,2775 Laurel St, Vancouver, BC V5Z 1M9, Canada.
C3 University of British Columbia; University of British Columbia;
   University of British Columbia; University of British Columbia;
   University of British Columbia; University of British Columbia;
   University of British Columbia; University of British Columbia
RP Jefferies, WA (通讯作者)，Univ British Columbia, Michael Smith Labs, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada.
EM wilf@msl.ubc.ca
FU UBC Centre for Blood Research Graduate Student Award; William and
   Dorothy Gilbert Graduate Scholarship in Biomedical Sciences; Canadian
   Institutes of Health Research [MOP-133635]; W. Garfield Weston
   Foundation [RR161038]; Pearson (University of Victoria)
FX Funding: CSBS was the recipient of a UBC Centre for Blood Research
   Graduate Student Award and the William and Dorothy Gilbert Graduate
   Scholarship in Biomedical Sciences; WAJ was supported by grants from the
   Canadian Institutes of Health Research (MOP-133635) and by the W.
   Garfield Weston Foundation (RR161038). The funding sources had no role
   in the study design, data collection, analysis or interpretation of
   data, or in the writing of the paper. The authors wish to acknowledge
   the very helpful editorial comments on this manuscript by Professor
   TerryW. Pearson (University of Victoria).
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NR 56
TC 6
Z9 6
U1 2
U2 6
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD SEP
PY 2021
VL 71
AR 103503
DI 10.1016/j.ebiom.2021.103503
EA SEP 2021
PG 14
WC Medicine, General & Internal; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Research & Experimental Medicine
GA WD5KU
UT WOS:000704980100009
PM 34534764
OA Green Published
DA 2022-11-30
ER

PT J
AU Mulfaul, K
   Giacalone, JC
   Voigt, AP
   Riker, MJ
   Ochoa, D
   Han, IC
   Stone, EM
   Mullins, RF
   Tucker, BA
AF Mulfaul, Kelly
   Giacalone, Joseph C.
   Voigt, Andrew P.
   Riker, Megan J.
   Ochoa, Dalyz
   Han, Ian C.
   Stone, Edwin M.
   Mullins, Robert F.
   Tucker, Budd A.
TI Stepwise differentiation and functional characterization of human
   induced pluripotent stem cell-derived choroidal endothelial cells
SO STEM CELL RESEARCH & THERAPY
LA English
DT Article
DE Induced pluripotent stem cells (iPSCs); Choroid; Choroidal endothelial
   cells (CECs); Age-related macular degeneration (AMD); Connective tissue
   growth factor (CTGF)
ID TISSUE GROWTH-FACTOR; MACULAR-DEGENERATION; EXPRESSION; EYES
AB BackgroundEndothelial cells (ECs) are essential regulators of the vasculature, lining arteries, veins, and capillary beds. While all ECs share a number of structural and molecular features, heterogeneity exists depending on their resident tissue. ECs lining the choriocapillaris in the human eye are lost early in the pathogenesis of age-related macular degeneration (AMD), a common and devastating form of vision loss. In order to study the mechanisms leading to choroidal endothelial cell (CEC) loss and to develop reagents for repairing the choroid, a reproducible in vitro model, which closely mimic CECs, is needed. While a number of protocols have been published to direct induced pluripotent stem cells (iPSCs) into ECs, the goal of this study was to develop methods to differentiate iPSCs into ECs resembling those found in the human choriocapillaris specifically.MethodsWe transduced human iPSCs with a CDH5p-GFP-ZEO lentiviral vector and selected for transduced iPSCs using blasticidin. We generated embryoid bodies (EBs) from expanded iPSC colonies and transitioned from mTESR (TM) 1 to EC media. One day post-EB formation, we induced mesoderm fate commitment via addition of BMP-4, activin A, and FGF-2. On day 5, EBs were adhered to Matrigel-coated plates in EC media containing vascular endothelial cell growth factor (VEGF) and connective tissue growth factor (CTGF) to promote CEC differentiation. On day 14, we selected for CECs using either zeocin resistance or anti-CD31 MACS beads. We expanded CECs post-selection and performed immunocytochemical analysis of CD31, carbonic anhydrase IV (CA4), and RGCC; tube formation assays; and transmission electron microscopy to access vascular function.ResultsWe report a detailed protocol whereby we direct iPSC differentiation toward mesoderm and utilize CTGF to specify CECs. The CDH5p-GFP-ZEO lentiviral vector facilitated the selection of iPSC-derived ECs that label with antibodies directed against CD31, CA4, and RGCC; form vascular tubes in vitro; and migrate into empty choroidal vessels. CECs selected using either antibiotic selection or CD31 MACS beads showed similar characteristics, thereby making this protocol easily reproducible with or without lentiviral vectors.ConclusionECs generated following this protocol exhibit functional and biochemical characteristics of CECs. This protocol will be useful for developing in vitro models toward understanding the mechanisms of CEC loss early in AMD.
C1 [Mulfaul, Kelly; Giacalone, Joseph C.; Voigt, Andrew P.; Riker, Megan J.; Ochoa, Dalyz; Han, Ian C.; Stone, Edwin M.; Mullins, Robert F.; Tucker, Budd A.] Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.
   [Mulfaul, Kelly; Giacalone, Joseph C.; Voigt, Andrew P.; Riker, Megan J.; Ochoa, Dalyz; Han, Ian C.; Stone, Edwin M.; Mullins, Robert F.; Tucker, Budd A.] Univ Iowa, Inst Vis Res, Iowa City, IA 52242 USA.
C3 University of Iowa; University of Iowa
RP Tucker, BA (通讯作者)，Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.; Tucker, BA (通讯作者)，Univ Iowa, Inst Vis Res, Iowa City, IA 52242 USA.
EM Budd-Tucker@uiowa.edu
RI Mullins, Robert F/I-6717-2013
OI Han, Ian/0000-0002-2371-727X; Stone, Edwin M./0000-0003-3343-4414;
   Giacalone, Joseph/0000-0003-4404-9749; Tucker, Budd/0000-0003-2178-1742;
   Mullins, Robert/0000-0002-5006-0891
FU National Institutes of Health [EY-024605, EY-025580]; Elmer and Sylvia
   Sramek Charitable Foundation
FX This research was funded by the National Institutes of Health, grants
   EY-024605 and EY-025580, and the Elmer and Sylvia Sramek Charitable
   Foundation.
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NR 32
TC 9
Z9 9
U1 0
U2 5
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1757-6512
J9 STEM CELL RES THER
JI Stem Cell Res. Ther.
PD SEP 23
PY 2020
VL 11
IS 1
AR 409
DI 10.1186/s13287-020-01903-4
PG 10
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA NV9RL
UT WOS:000574648900002
PM 32967716
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Fan, JW
   Shen, WY
   Lee, SR
   Mathai, AE
   Zhang, R
   Xu, GZ
   Gillies, MC
AF Fan, Jiawen
   Shen, Weiyong
   Lee, So-Ra
   Mathai, Ashish Easow
   Zhang, Rui
   Xu, Gezhi
   Gillies, Mark C.
TI Targeting the Notch and TGF-beta signaling pathways to prevent retinal
   fibrosis in vitro and in vivo
SO THERANOSTICS
LA English
DT Article
DE Notch; transforming growth factor beta; signalling pathway; Muller
   cells; retina; fibrosis
ID EPITHELIAL-MESENCHYMAL TRANSITION; SODIUM IODATE; GROWTH-FACTOR; CARDIAC
   FIBROSIS; MULLER CELLS; RPE CELLS; VEGF-A; NEOVASCULARIZATION;
   PROLIFERATION; DEGENERATION
AB Rationale: The Notch and transforming growth factor-beta (TGF beta) signaling pathways are two intracellular mechanisms that control fibrosis in general but whether they play a major role in retinal fibrosis is less clear. Here we study how these two signaling pathways regulate Muller cell-dominated retinal fibrosis in vitro and in vivo.
   Methods: Human MIO-M1 Muller cells were treated with Notch ligands and TGF beta 1, either alone or in combination. Western blots were performed to study changes in gamma-secretase proteases, Notch downstream effectors, endogenous TGF beta 1, phosphorylated Smad3 (p-Smad3) and extracellular matrix (ECM) proteins. We also studied the effects of RO4929097, a selective gamma-secretase inhibitor, on expression of ECM proteins after ligand stimulation. Muller cell viability was studied by AlamarBlue and cytotoxicity by lactate cytotoxicity assays. Finally, we studied changes in Notch and TGF beta signaling and tested the effect of intravitreal injections of the Notch pathway inhibitor RO4929097 on retinal fibrosis resulted from Sodium iodate (NaIO3)-induced retinal injury in mice. We also studied the safety of intravitreal injections of RO4929097 in normal mice.
   Results: Treatment of Muller cells with Notch ligands upregulated gamma-secretase proteases and Notch downstream effectors, with increased expression of endogenous TGF beta 1, TGF beta receptors and p-Smad3. TGF beta 1 upregulated the expression of proteins associated with both signaling pathways in a similar manner. Notch ligands and TGF beta 1 had additive effects on overexpression of ECM proteins in Muller cells which were inhibited by RO4929097. Notch and TGF beta ligands stimulated Muller cell proliferation which was inhibited by RO4929097 without damaging the cells. NaIO3-induced retinal injury activated both Notch and TGF beta signaling pathways in vivo. Intravitreal injection of RO4929097 prevented Muller cell gliosis and inhibited overexpression of ECM proteins in this murine model. We found no safety concerns for up to 17 days after an intravitreal injection of RO4929097.
   Conclusions: Inhibiting Notch signaling might be an effective way to prevent retinal fibrosis. This study is of clinical significance in developing a treatment for preventing fibrosis in proliferative vitreoretinopathy, proliferative diabetic retinopathy and wet age-related macular degeneration.
C1 [Fan, Jiawen; Shen, Weiyong; Lee, So-Ra; Mathai, Ashish Easow; Zhang, Rui; Gillies, Mark C.] Univ Sydney, Sydney Med Sch, Save Sight Inst, Discipline Ophthalmol, Sydney, NSW, Australia.
   [Fan, Jiawen; Xu, Gezhi] Fudan Univ, Dept Ophthalmol & Vis Sci, Eye & ENT Hosp, Shanghai Med Coll,State Hlth Minist, Shanghai, Peoples R China.
   [Fan, Jiawen; Xu, Gezhi] Fudan Univ, Key Lab Myopia, Eye & ENT Hosp, Shanghai Med Coll,State Hlth Minist, Shanghai, Peoples R China.
C3 University of Sydney; Fudan University; Fudan University
RP Shen, WY; Gillies, MC (通讯作者)，Univ Sydney, Save Sight Inst, Sydney, NSW 2000, Australia.
EM weiyongshen1@gmail.com; mark.gillies@sydney.edu.au
FU Ophthalmic Research Institute of Australia; Commercial Development
   Innovation Partnership, the University of Sydney; Australia Endeavour
   Cheung Kong Research Fellowship; National Health and Medical Research
   Council (Australia) Practitioner Fellowship
FX The study was supported by grants from the Ophthalmic Research Institute
   of Australia and Commercial Development Innovation Partnership, the
   University of Sydney. Jiawen Fan was supported by an Australia Endeavour
   Cheung Kong Research Fellowship. Mark Gillies is a fellow of Sydney
   Medical School Foundation and supported by a National Health and Medical
   Research Council (Australia) Practitioner Fellowship.
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NR 71
TC 22
Z9 22
U1 1
U2 3
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2020
VL 10
IS 18
BP 7956
EP 7973
DI 10.7150/thno.45192
PG 18
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA MK1AE
UT WOS:000548517800002
PM 32724452
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Vo, TA
   Abedi, S
   Schneider, K
   Chwa, M
   Kenney, MC
AF Vo, Thomas A.
   Abedi, Sina
   Schneider, Kevin
   Chwa, Marilyn
   Kenney, M. Cristina
TI Effects of bevacizumab, ranibizumab, and aflibercept on phagocytic
   properties in human RPE cybrids with AMD versus normal mitochondria
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Phagocytosis; Latex beads; Bevacizumab; Ranibizumab; Aflibercept;
   Anti-VEGF; Cybrids; Retinal pigment epithelium; Mitochondria;
   Age-related macular degeneration
ID RETINAL-PIGMENT EPITHELIUM; AGE; CELLS; DYSFUNCTION; INHIBITION
AB Purpose: A critical biological function of retina pigment epithelium (RPE) cells is phagocytosis of photoreceptor outer segment (POS) disc membranes. Mitochondrial damage and dysfunction are associated with RPE cells of age-related macular degeneration (AMD) retinas. In this study, we use a transmitochondrial cybrid model to compare the phagocytic properties of RPE cells that contain AMD mitochondria versus age-matched normal mitochondria and their response to treatment with anti-vascular endothelial growth factor (VEGF) drugs: bevacizumab, ranibizumab, and aflibercept.
   Methods: Cybrids, which are cell lines with identical nuclei but mitochondria (mt) from different subjects, are created by fusing mtDNA depleted ARPE-19 cells with platelets from AMD or age-matched normal patients. AMD (n = 5) and normal (n = 5) cybrids were treated with 1 run fluorescent latex beads (1.52 x 10(7) beads/mL) and either 2.09 mu M of bevacizumab, 2.59 mu M of ranibizumab, or 5.16 mu M of aflibercept. These doses of anti-VEGF drugs are equivalent to intravitreal injections given to AMD patients with choroidal neovascularization. Flow cytometry was performed using the ImageStreamX Mark II to assess phagocytic bead-uptake. The average fold values for bead-uptake and SEM were calculated using GraphPad Prism software.
   Results: Normal cybrids showed decreased bead-uptake with a fold value of 0.65 +/- 0.103 (p = 0.01) after treatment with bevacizumab, 0.80 +/- 0.034 (p = 0.0003) with ranibizumab, and 0.81 +/- 0.053 (p = 0.007) with aflibercept compared to the untreated normal cybrids (baseline fold of 1). The bevacizumab-treated, ranibizumab-treated, and aflibercept-treated AMD cybrids had decreased bead-uptake with a fold value of 0.71 +/- 0.061 (p = 0.001), 0.70 +/- 0.101 (p = 0.02), and 0.74 +/- 0.125 (p = 0.07), respectively, compared to the untreated AMD cybrids (baseline fold of 1).
   Conclusions: Our initial findings showed that when treated with bevacizumab and ranibizumab, both AMD cybrids and age-matched normal cybrids had a significant decrease in bead-uptake. A similar decrease in bead-uptake was found in normal cybrids treated with aflibercept and while the AMD values trended lower, they were not significant. This data suggests that anti-VEGF drugs can cause loss of phagocytic function.
C1 [Vo, Thomas A.; Abedi, Sina; Schneider, Kevin; Chwa, Marilyn; Kenney, M. Cristina] Univ Calif Irvine, Gavin Herbert Eye Inst, Hewitt Hall,Room 2028,843 Hlth Sci Rd, Irvine, CA 92697 USA.
   [Kenney, M. Cristina] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA.
C3 University of California System; University of California Irvine;
   University of California System; University of California Irvine
RP Kenney, MC (通讯作者)，Univ Calif Irvine, Gavin Herbert Eye Inst, Hewitt Hall,Room 2028,843 Hlth Sci Rd, Irvine, CA 92697 USA.
EM mkenney@uci.edu
RI Abedi, Sina/AFQ-5495-2022
FU Research to Prevent Blindness (RPB) Medical Student Eye Research
   Fellowship; Gavin Herbert Eye Institute; Discovery Eye Foundation; Polly
   and Michael Smith, Iris and B. Gerald Cantor Foundation; Max Factor
   Family Foundation; Research to Prevent Blindness; Institute for Clinical
   and Translational Science (ICTS) at University of California Irvine;
   NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001414]
   Funding Source: NIH RePORTER
FX This work was supported by the Research to Prevent Blindness (RPB)
   Medical Student Eye Research Fellowship (awarded to TAV) and the Gavin
   Herbert Eye Institute, which is an institutional RPB grant recipient.
   The research was supported by the Discovery Eye Foundation, Polly and
   Michael Smith, Iris and B. Gerald Cantor Foundation and Max Factor
   Family Foundation. Supported in part by an Unrestricted Grant from
   Research to Prevent Blindness to Gavin Herbert Eye Institute. We
   acknowledge the support of the Institute for Clinical and Translational
   Science (ICTS) at University of California Irvine.
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NR 36
TC 5
Z9 5
U1 0
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD DEC
PY 2018
VL 177
BP 112
EP 116
DI 10.1016/j.exer.2018.07.025
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HE7OO
UT WOS:000453628000013
PM 30071215
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Kleiner, J
   Hollborn, M
   Wiedemann, P
   Bringmann, A
AF Kleiner, Jana
   Hollborn, Margrit
   Wiedemann, Peter
   Bringmann, Andreas
TI Activator protein-1 contributes to the NaCl-induced expression of VEGF
   and PlGF in RPE cells
SO MOLECULAR VISION
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; AGE-RELATED MACULOPATHY; EXPERIMENTAL
   CHOROIDAL NEOVASCULARIZATION; PATHOGENIC T(H)17 CELLS; PLACENTAL
   GROWTH-FACTOR; MACULAR DEGENERATION; RISK-FACTORS; C-JUN;
   CARDIOVASCULAR-DISEASE; DIETARY SALT
AB Purpose: Systemic hypertension is a risk factor of neovascular age-related macular degeneration; consumption of dietary salt resulting in extracellular hyperosmolarity is a main cause of hypertension. Extracellular hyperosmolarity was shown to induce expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), in RPE cells. The aim of the present study was to determine whether the hyperosmotic expression of growth factor genes in RPE cells is mediated by activator protein-1 (AP-1), and whether c-Fos and c-Jun genes are regulated by extracellular osmolarity.
   Methods: Hyperosmotic media were made up with the addition of NaCl or sucrose. Gene expression was quantified with real-time reverse transcription (RT)-PCR, and protein secretion was investigated with enzyme-linked immunosorbent assay (ELISA). Nuclear factor of activated T cell 5 (NFAT5) was depleted with siRNA. DNA binding of AP-1 protein was evaluated with electrophoretic mobility shift assay (EMSA).
   Results: High NaCl and the addition of sucrose triggered expression of the c-Fos gene, but not of the c-Jun gene. High NaCl also increased the levels of c-Fos and phosphorylated c-Jun proteins and the level of DNA binding of AP-1. Hypoosmolarity decreased the expression of the c-Fos and c-Jun genes. NaCl-induced expression of the c-Fos gene was in part mediated by NFAT5. Autocrine/paracrine activation of fibroblast growth factor and adenosine A(1) receptors is involved in mediating NaCl-induced expression of the c-Fos gene. Pharmacological inhibition of the AP-1 activity decreased the NaCl-induced expression of the HIF-1 alpha, NFAT5, VEGF, PlGF, and TGF-beta 2 genes, and prevented the NaCl-induced secretion of PlGF but not of VEGF.
   Conclusions: The data indicate that AP-1 is activated in RPE cells in response to extracellular hyperosmolarity and mediates in part via the NaCl-induced expression of VEGF and PlGF, and secretion of PlGF. It is suggested that high consumption of dietary salt may exacerbate the angiogenic response of RPE cells in part via activation of AP-1.
C1 [Bringmann, Andreas] Univ Leipzig, Dept Ophthalmol, Liebigstr 10-14, D-04103 Leipzig, Germany.
   [Bringmann, Andreas] Univ Leipzig, Eye Hosp, Liebigstr 10-14, D-04103 Leipzig, Germany.
C3 Leipzig University; Leipzig University
RP Bringmann, A (通讯作者)，Univ Leipzig, Dept Ophthalmol, Liebigstr 10-14, D-04103 Leipzig, Germany.; Bringmann, A (通讯作者)，Univ Leipzig, Eye Hosp, Liebigstr 10-14, D-04103 Leipzig, Germany.
EM bria@medizin.uni-leipzig.de
FU Geschwister Freter Stiftung (Hannover, Germany)
FX The authors thank Ute Weinbrecht for excellent technical assistance.
   This work was supported by a grant from the Geschwister Freter Stiftung
   (Hannover, Germany).
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NR 55
TC 6
Z9 6
U1 0
U2 0
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD OCT 9
PY 2018
VL 24
BP 647
EP 666
PG 20
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA GW5LS
UT WOS:000446976800001
PM 30310263
DA 2022-11-30
ER

PT J
AU Atchison, EA
   Wood, KM
   Mattox, CG
   Barry, CN
   Lum, F
   MacCumber, MW
AF Atchison, Elizabeth A.
   Wood, Kevin M.
   Mattox, Cynthia G.
   Barry, Catherine N.
   Lum, Flora
   MacCumber, Mathew W.
TI The Real-World Effect of Intravitreous Anti-Vascular Endothelial Growth
   Factor Drugs on Intraocular Pressure An Analysis Using the IRIS Registry
SO OPHTHALMOLOGY
LA English
DT Article
ID DIABETIC MACULAR EDEMA; RANIBIZUMAB INJECTIONS; DEGENERATION;
   BEVACIZUMAB; TRIAL; AFLIBERCEPT
AB Purpose: To identify sustained differences in intraocular pressure (IOP) after intravitreous injections of antievascular endothelial growth factor (VEGF) drugs.
   Design: Database study.
   Participants: Patients seeing an ophthalmic provider who contributes to the database.
   Methods: We identified a total of 23 776 unique patients who received only a single type of anti-VEGF medication (bevacizumab, aflibercept, or ranibizumab) by injection in the right eye in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Subgroups included patients with age-related macular degeneration only and patients who had not received an anti-VEGF injection for at least 1 year before the study. We examined those with at least 12, 18, and 25 injections for each of these 3 medications. For all groups, we used fellow, untreated eyes for comparison.
   Main Outcome Measures: The mean change in IOP from baseline at a minimum of 1 year of follow-up and the proportion of eyes with a clinically significant IOP increase (defined as sustained rise of at least 6 mmHg to an IOP of more than 21 mmHg).
   Results: All patients in all groups receiving all drugs showed a decrease in IOP from baseline, with a mean of 0.9 mmHg in treated eyes compared with an average decrease of 0.2 mmHg in fellow untreated eyes, a statistically significant difference. A generalized linear model accounting for confounders associated bevacizumab with slightly less lowering of IOP than aflibercept and ranibizumab in most subgroups. A clinically significant IOP increase was seen in 2.6% of eyes receiving injections compared with 1.5% in the associated untreated fellow eyes. Clinically significant IOP increases occurred at a rate of 1.9%, 2.8%, and 2.8% for aflibercept, ranibizumab, and bevacizumab, respectively, which was significantly higher than untreated fellow eyes for bevacizumab and ranibizumab, but not for aflibercept.
   Conclusions: These analyses from real-world data indicate that anti-VEGF intravitreous injections are associated with a small but statistically significant decrease in IOP over time. A proportion of patients, on average 2.6%, experienced a sustained clinically significant IOP rise with these drugs overall compared with 1.5% in the fellow untreated eyes. However, such an increase was not seen with aflibercept. (C) 2018 by the American Academy of Ophthalmology
C1 [Atchison, Elizabeth A.; MacCumber, Mathew W.] Rush Univ, Med Ctr, Dept Ophthalmol, Chicago, IL 60612 USA.
   [Wood, Kevin M.; Barry, Catherine N.; Lum, Flora] Amer Acad Ophthalmol, San Francisco, CA USA.
   [Mattox, Cynthia G.] Tufts Univ, Sch Med, New England Eye Ctr, Boston, MA 02111 USA.
C3 Rush University; Tufts University
RP MacCumber, MW (通讯作者)，Rush Univ, Illinois Retina Associates, 2847 North Sheridan Rd,Suite 900, Chicago, IL 60657 USA.
EM mmaccumber@illinoisretina.com
OI Atchison, Elizabeth/0000-0002-5848-9836
FU Allergan; Alcon; Aerie; Genentech; Regeneron
FX The author(s) have made the following disclosure(s): C.G.M.: Consulting
   fees and grants - Allergan, Alcon, Aerie.; M.W.M.: Consulting fees and
   grants - Genentech, Regeneron.
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NR 26
TC 35
Z9 36
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAY
PY 2018
VL 125
IS 5
BP 676
EP 682
DI 10.1016/j.ophtha.2017.11.027
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GD5PL
UT WOS:000430558800016
PM 29336897
DA 2022-11-30
ER

PT J
AU Dolz-Marco, R
   Litts, KM
   Tan, ACS
   Freund, KB
   Curcio, CA
AF Dolz-Marco, Rosa
   Litts, Katie M.
   Tan, Anna C. S.
   Freund, K. Bailey
   Curcio, Christine A.
TI The Evolution of Outer Retinal Tubulation, a Neurodegeneration and
   Gliosis Prominent in Macular Diseases
SO OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL-COHERENCE-TOMOGRAPHY; PIGMENT-EPITHELIUM; GEOGRAPHIC ATROPHY;
   GLIAL-CELLS; CHOROIDAL NEOVASCULARIZATION; FUNDUS AUTOFLUORESCENCE;
   PHOTORECEPTOR ROSETTES; FEMALE CARRIER; MULLER CELLS; DEGENERATION
AB Purpose: To document outer retinal tubulation (ORT) formation in advanced retinal disorders.
   Design: Retrospective, observational study.
   Participants: Consecutive cases with retinal diseases showing outer retinal disruption and atrophy of the retinal pigment epithelium (RPE) associated with ORT on spectral-domain (SD) optical coherence tomography (OCT) at the final available visit.
   Methods: Cross-sectional SD OCT scans showing ORT at the last available visit were compared with eye-tracked baseline scans. Only patients showing the formation of ORT over time with absence of ORT at baseline were analyzed.
   Main Outcome Measures: Steps in ORT formation based on shapes of the external limiting membrane (ELM) descent (flat, curved, reflected, and scrolled) at the border of outer retinal and RPE atrophy, ORT characteristics (open, closed), and time between steps through a long-term follow-up.
   Results: From 170 eyes of 86 patients with ORT, 38 eyes of 30 patients (11 men, 19 women) with a mean age of 78.87 years (range, 56-96 years) met inclusion criteria. Of these 38 eyes, 23 (60%) had geographic atrophy secondary to age-related macular degeneration (AMD) and 2 eyes (5%) had geographic atrophy secondary to pattern dystrophy. Twelve eyes (32%) had neovascular AMD and 1 eye (3%) had neovascularization secondary to pseudoxanthoma elasticum, all showing similar ORT formative steps. Seventy-three different retinal areas (1434 cross-sectional images) were analyzed over a mean follow-up of 69.5 months (range, 21-93 months). At 73 borders, grading of eye-tracked follow-up SD OCT line scans showed a flat ELM descent at least once at 34 borders (47%), a curved ELM at 47 borders (64%), a reflected ELM at 37 borders (51%), and a scrolled ELM at 24 borders (33%). Of 81 ORTs, 73 (90%) were closed and 8 (10%) were open. The mean time for ORT formation was 14.9 months (range, 1.4-71.3 months).
   Conclusions: We propose progressive steps in the development of ORT and analyze the time of progression between these steps. Analyzing the borders of atrophy to determine the origin of ORT provides new insights into the pathophysiology of advanced retinal disease highlighting a role for Muller cells and may inform future therapeutic strategies. (C) 2017 by the American Academy of Ophthalmology
C1 [Dolz-Marco, Rosa; Tan, Anna C. S.; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, 460 Pk Ave, New York, NY 10022 USA.
   [Dolz-Marco, Rosa; Tan, Anna C. S.; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA.
   [Dolz-Marco, Rosa] Univ & Polytech La Hosp Fe, Unit Macula, Hlth Res Inst, Valencia, Spain.
   [Litts, Katie M.; Curcio, Christine A.] Univ Alabama Birmingham, Sch Med, Dept Ophthalmol, Birmingham, AL USA.
   [Tan, Anna C. S.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Freund, K. Bailey] Columbia Univ Coll Phys & Surg, Dept Ophthalmol, Edward S Harkness Eye Inst, New York, NY 10032 USA.
   [Freund, K. Bailey] NYU, Dept Ophthalmol, Sch Med, 550 1St Ave, New York, NY 10016 USA.
C3 Vitreous Retina Macula Consultants of New York; Manhattan Eye Ear &
   Throat Hospital; University of Alabama System; University of Alabama
   Birmingham; National University of Singapore; Singapore National Eye
   Center; Columbia University; New York University
RP Freund, KB (通讯作者)，Vitreous Retina Macula Consultants New York, 460 Pk Ave, New York, NY 10022 USA.
EM kbfnyf@aol.com
RI Litts, Katie M/AAK-1564-2021; Freund, K. Bailey/V-7488-2018
OI Litts, Katie M/0000-0001-6707-8273; Dolz-Marco,
   Rosa/0000-0002-2963-2541; Freund, K. Bailey/0000-0002-7888-9773
FU LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and
   Throat Hospital, New York, New York; Macula Foundation, Inc., New York,
   New York; National Institutes of Health, Bethesda, Maryland
   [R01EY06019]; EyeSight Foundation of Alabama; International Retinal
   Research Foundation; Edward N. and Della L. Thome Foundation; Arnold and
   Mabel Beckman Initiative for Macular Research; Research to Prevent
   Blindness, Inc., New York, New York; Vision Science Training Program at
   University of Alabama at Birmingham, Birmingham, Alabama
FX Supported by the LuEsther T. Mertz Retinal Research Center, Manhattan
   Eye, Ear, and Throat Hospital, New York, New York; and The Macula
   Foundation, Inc., New York, New York; the National Institutes of Health,
   Bethesda, Maryland (grant no.: R01EY06019 [C.A.C.]); EyeSight Foundation
   of Alabama; International Retinal Research Foundation; Edward N. and
   Della L. Thome Foundation; the Arnold and Mabel Beckman Initiative for
   Macular Research; Research to Prevent Blindness, Inc., New York, New
   York; and the Vision Science Training Program at University of Alabama
   at Birmingham, Birmingham, Alabama (K.M.L.).
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   [No title captured]
NR 72
TC 41
Z9 42
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD SEP
PY 2017
VL 124
IS 9
BP 1353
EP 1367
DI 10.1016/j.ophtha.2017.03.043
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FD8RT
UT WOS:000407792500019
PM 28456420
DA 2022-11-30
ER

PT J
AU Pozet, A
   Lejeune, C
   Bonnet, M
   Dabakuyo, S
   Dion, M
   Fagnoni, P
   Gaimard, M
   Imbert, G
   Nerich, V
   Foubert, A
   Chotard, M
   Bonin, M
   Anota, A
   Bonnetain, F
AF Pozet, Astrid
   Lejeune, Catherine
   Bonnet, Magalie
   Dabakuyo, Sandrine
   Dion, Michele
   Fagnoni, Philippe
   Gaimard, Maryse
   Imbert, Genevieve
   Nerich, Virginie
   Foubert, Audrey
   Chotard, Morgane
   Bonin, Marie
   Anota, Amelie
   Bonnetain, Franck
TI Evaluation of efficacy and efficiency of a pragmatic intervention by a
   social worker to support informal caregivers of elderly patients (The
   ICE Study): study protocol for a randomized controlled trial
SO TRIALS
LA English
DT Article
DE Informal caregivers; Elderly; Health-related quality of life;
   Cost-utility; Randomized study; Longitudinal cohort study; Cancer;
   Chronic disease
ID QUALITY-OF-LIFE; SF-36 HEALTH SURVEY; SHORT-FORM; SURVEY QUESTIONNAIRE;
   VALIDATION; DEMENTIA; TRANSLATION; RELIABILITY; ADAPTATION; DEPRESSION
AB Background: Medical progress and the lifestyle modification have prolonged life expectancy, despite the development of chronic diseases. Support and care for older subjects are often provided by a network of informal caregivers composed of family, friends and neighbors, who are essential in helping older persons to continue living at home. It has been shown that the extent and diversity of informal tasks may jeopardize the physical, mental and social wellbeing of caregivers.
   Methods/design: The aim of the Informal Carers of Elderly cohort is to define, through a longitudinal study, profiles of caregivers of older patients with a diagnosis of one of the following diseases: cancer (breast, prostate, colorectal), neurodegenerative diseases (Parkinson's disease, Alzheimer's disease and similar diseases), neurovascular diseases (stroke), sensory diseases (age-related macular degeneration (AMD)) and heart disease (heart failure). Patients must be at least 60 years old and living in the region of Burgundy-Franche-Comte (France). By following the different phases of the caregiving relationship from the announcement of the diagnosis, it will be possible to assess the quality of life of caregivers, coping strategies, levels of anxiety and depression, social support and the extent of their burden. We will also evaluate the efficacy and efficiency of the implementation of a pragmatic intervention by a social worker to help informal caregivers, through a randomized interventional trial nested in the cohort. Qualitative approaches aimed at studying the caregiver/patient relationship, and situations leading to breakdown of the caregiver relationship will be also undertaken.
   Discussion: Through an analytical and longitudinal definition of profiles of informal caregivers, this study will gather detailed information on their life courses and their health trajectory by identifying consequences associated with the concept of their role as carers. In addition, the randomized interventional trial will explore the relevance of the implementation of a supportive intervention by a social worker to help caregivers. These data will help to identify strategies that could be used to improve the existing sources of aid and to propose new approaches to help caregivers. This study will provide the opportunity to identify the most relevant means of support adapted to caregivers, and provide an impulse for new health care policies.
C1 [Pozet, Astrid; Imbert, Genevieve; Foubert, Audrey; Chotard, Morgane; Anota, Amelie; Bonnetain, Franck] Univ Hosp Besancon, Methodol & Qual Life Oncol Unit, INSERM, UMR 1098, Besancon, France.
   [Lejeune, Catherine] Univ Burgundy, INSERM, Epidemiol & Rech Clin Oncol Digest U866, Dijon, France.
   [Bonnet, Magalie] Univ Franche Comte, UFR Sci Langage Homme & Soc, Besancon, France.
   [Dabakuyo, Sandrine] Ctr Georges Francois Leclerc, EA 4184, Dijon, France.
   [Dion, Michele; Gaimard, Maryse] CNRS, UFR Sci Humaines & Soci, UMR 7366, Ctr Georges Chevrier, Dijon, France.
   [Fagnoni, Philippe] Univ Burgundy, Fac Pharm, EA 4184, Dijon, France.
   [Nerich, Virginie] INSERM, U1098, Interact Hote Greffon & Ingn Cellulaire & Genique, Besancon, France.
   [Bonin, Marie] Pole Gerontol Interreg Bourgogne & Franche Comte, Besancon, France.
   [Anota, Amelie; Bonnetain, Franck] French Natl Platform Qual Life & Canc, Besancon, France.
   [Pozet, Astrid] Univ Hosp Jean Minjoz, Methodol & Qual Life Oncol Unit, Blvd Fleming, F-25030 Besancon, France.
C3 CHU Besancon; Institut National de la Sante et de la Recherche Medicale
   (Inserm); Universite de Franche-Comte; Institut Agro; AgroSup Dijon;
   Institut National de la Sante et de la Recherche Medicale (Inserm);
   Universite de Bourgogne; Universite de Franche-Comte; UNICANCER; Centre
   Georges-Francois Leclerc; Universite de Bourgogne; Centre National de la
   Recherche Scientifique (CNRS); CNRS - Institute for Humanities & Social
   Sciences (INSHS); Universite de Bourgogne; Universite de Bourgogne;
   Universite de Franche-Comte; Institut National de la Sante et de la
   Recherche Medicale (Inserm); Universite de Franche-Comte; CHU Besancon
RP Pozet, A (通讯作者)，Univ Hosp Besancon, Methodol & Qual Life Oncol Unit, INSERM, UMR 1098, Besancon, France.; Pozet, A (通讯作者)，Univ Hosp Jean Minjoz, Methodol & Qual Life Oncol Unit, Blvd Fleming, F-25030 Besancon, France.
EM apozet@chu-besancon.fr
RI Janson, Patrick/AAC-7581-2022; Dabakuyo - Yonli, Tienhan
   Sandrine/Q-2150-2018
OI NERICH, Virginie/0000-0002-0351-6040; Dabakuyo - Yonli, Tienhan
   Sandrine/0000-0002-8191-1222; Magalie, Bonnet
   Llompart/0000-0002-0898-4935; Lejeune, Catherine/0000-0001-7351-0798;
   POZET, Astrid/0000-0003-4371-1112
FU InCA (Institut National du CAncer); ANR (Agence Nationale de la
   Recherche); La Ligue Contre le Cancer; Roche Foundation; CNSA (Caisse
   Nationale de Solidarite pour l'Autonomie); Novartis Pharma
FX The study is funded through grants provided by the InCA (Institut
   National du CAncer), the ANR (Agence Nationale de la Recherche), La
   Ligue Contre le Cancer, Roche Foundation, the CNSA (Caisse Nationale de
   Solidarite pour l'Autonomie) and Novartis Pharma. Funders had no
   involvement in the design and were not involved in any aspect of
   manuscript development or approval.
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   [No title captured]
NR 51
TC 9
Z9 9
U1 1
U2 56
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD NOV 3
PY 2016
VL 17
AR 531
DI 10.1186/s13063-016-1622-8
PG 12
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Research & Experimental Medicine
GA ED0LX
UT WOS:000388535100001
PM 27881145
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Stiles, M
   Moiseyev, GP
   Budda, ML
   Linens, A
   Brush, RS
   Qi, H
   White, GL
   Wolf, RF
   Ma, JX
   Floyd, R
   Anderson, RE
   Mandal, NA
AF Stiles, Megan
   Moiseyev, Gennadiy P.
   Budda, Madeline L.
   Linens, Annette
   Brush, Richard S.
   Qi, Hui
   White, Gary L.
   Wolf, Roman F.
   Ma, Jian-xing
   Floyd, Robert
   Anderson, Robert E.
   Mandal, Nawajes A.
TI PBN (Phenyl-N-Tert-Butylnitrone)-Derivatives Are Effective in Slowing
   the Visual Cycle and Rhodopsin Regeneration and in Protecting the Retina
   from Light-Induced Damage
SO PLOS ONE
LA English
DT Article
ID TERT-BUTYLNITRONE PROTECTS; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   ISOMEROHYDROLASE ACTIVITY; CONGENITAL AMAUROSIS; PIGMENT EPITHELIUM;
   RPE65 MUTATIONS; GLIOMA MODELS; VITAMIN-A; LIPOFUSCIN
AB A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE) cells in eyes affected by Stargardt's disease, age-related macular degeneration (AMD), and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN) inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs) such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP) administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG) and histological analysis showed that rats treated with PBNDs retained similar to 90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75-80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control). In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE) by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat retina from light damage. There is potential in developing these compounds as preventative therapeutics for the treatment of human retinal degenerations in which the accumulation of lipofuscin may be pathogenic.
C1 [Stiles, Megan; Linens, Annette; Brush, Richard S.; Qi, Hui; Anderson, Robert E.; Mandal, Nawajes A.] OUHSC, Dept Ophthalmol, Oklahoma City, OK 73104 USA.
   [Moiseyev, Gennadiy P.; Ma, Jian-xing] OUHSC, Dept Physiol, Oklahoma City, OK USA.
   [Budda, Madeline L.; Mandal, Nawajes A.] OUHSC, Dept Cell Biol, Oklahoma City, OK USA.
   [White, Gary L.; Wolf, Roman F.; Anderson, Robert E.] OUHSC, Dept Pathol, Oklahoma City, OK USA.
   [Ma, Jian-xing; Mandal, Nawajes A.] OUHSC, Dept Endocrinol & Diabet, Oklahoma City, OK USA.
   [Mandal, Nawajes A.] OUHSC, Oklahoma Ctr Neurosci, Oklahoma City, OK USA.
   [Stiles, Megan; Linens, Annette; Brush, Richard S.; Qi, Hui; Anderson, Robert E.; Mandal, Nawajes A.] Dean McGee Eye Inst, Oklahoma City, OK USA.
   [Floyd, Robert] Oklahoma Med Res Fdn, Expt Therapeut, Oklahoma City, OK 73104 USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; University of Oklahoma System; University of Oklahoma Health
   Sciences Center; University of Oklahoma System; University of Oklahoma
   Health Sciences Center; University of Oklahoma System; University of
   Oklahoma Health Sciences Center; University of Oklahoma System;
   University of Oklahoma Health Sciences Center; University of Oklahoma
   System; University of Oklahoma Health Sciences Center; Oklahoma Medical
   Research Foundation
RP Mandal, NA (通讯作者)，OUHSC, Dept Ophthalmol, Oklahoma City, OK 73104 USA.
EM mmandal@ouhsc.edu
FU Foundation Fighting Blindness (United States); Beckman Initiative for
   Macular Research; RPB; National Institutes of Health; NATIONAL EYE
   INSTITUTE [P30EY021725] Funding Source: NIH RePORTER
FX The research is conducted by the fundings from The Foundation Fighting
   Blindness (United States), Beckman Initiative for Macular Research, RPB
   and National Institutes of Health fundings. The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 50
TC 7
Z9 7
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 22
PY 2015
VL 10
IS 12
AR e0145305
DI 10.1371/journal.pone.0145305
PG 17
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CZ4SH
UT WOS:000367092500038
PM 26694648
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Aki, K
   Fujii, N
   Saito, T
   Fujii, N
AF Aki, Kenzo
   Fujii, Norihiko
   Saito, Takeshi
   Fujii, Noriko
TI Characterization of an antibody that recognizes peptides containing
   D-beta-aspartyl residues
SO MOLECULAR VISION
LA English
DT Article
ID ALPHA-A-CRYSTALLIN; ACID RACEMIZATION; HUMAN LENS; SIMULTANEOUS
   STEREOINVERSION; ISOMERIZATION; PROTEIN; SKIN; LOCALIZATION; ELASTIN
AB Purpose: Biologically uncommon D-beta-aspartyl (D-beta-Asp) residues have been detected in proteins from various human tissues from elderly donors and are connected with cataract, age-related macular degeneration, Alzheimer disease and UV-irradiated skin. In a previous study, we prepared a highly specific antibody against the peptide Gly-Leu-D-beta-Asp-Ala-Thr-Gly-Leu-D-beta-Asp-Ala-Thr-Gly-Leu-D-beta-Asp-Ala-Thr (designated peptide 3R) that corresponds to three repeats of positions 149-153 of human lens alpha A-crystallin. This antibody clearly distinguishes between the different configurations of the Asp residue in that it reacted strongly with the D-beta-Asp-containing peptides but did not react with L-alpha-Asp-, L-Asp-, L-beta-Asp-, or D-alpha-Asp-containing peptides. However, it remains unclear whether the antibody recognizes the amino acid sequences surrounding the D-beta-Asp residue. The purpose of the present study is to elucidate the sequence dependency of the epitope of the antigen.
   Methods: To clarify the properties of the anti-peptide 3R antibody, we used F-moc (9-fluorenylmethoxycarbonyl) solid phase chemistry to synthesize various peptides and analogs based on the peptides T18 (I(146)QTGLDATHAER(157)) and T6 (T(55)VLDAGISEVR(65)) which correspond to amino acid sequences 146-157 and 55-65, respectively of human alpha A-crystallin. The specificity of antibody was confirmed by ELISA (enzyme-linked immunosorbent assay) using these peptides.
   Results: The anti peptide 3R antibody specifically recognized D-alpha-Asp residues and does not react with other configurations of Asp such as the L-alpha, L-beta, D-alpha isomers in peptides. When the Ala in the peptide was replaced by other amino acid residues, the antibody did not react with the antigen. The antibody requires the sequence Leu-D-alpha-Asp-Ala to detect D-alpha-Asp containing proteins in living tissue.
   Conclusions: The anti peptide 3R antibody is a powerful and easy tool for detection of D-beta-Asp containing proteins in living tissues from patients with age-related diseases. However, to detect the D-beta-Asp containing proteins in the living tissues using the anti-peptide 3R antibody, the protein must contain the sequence Leu-D-beta-Asp-Ala.
C1 [Aki, Kenzo; Fujii, Norihiko; Saito, Takeshi; Fujii, Noriko] Kyoto Univ, Inst Res Reactor, Kumatori, Osaka 5900494, Japan.
C3 Kyoto University
RP Fujii, N (通讯作者)，Kyoto Univ, Inst Res Reactor, Kumatori, Osaka 5900494, Japan.
EM nfujii@rri.kyoto-u.ac.jp; nfujii@rri.kyoto-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan
FX This work was supported by a grant from the Ministry of Education,
   Culture, Sports, Science and Technology of Japan.
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NR 16
TC 2
Z9 2
U1 0
U2 1
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD APR 21
PY 2012
VL 18
IS 104-07
BP 996
EP 1003
PG 8
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 947MM
UT WOS:000304434100002
PM 22550393
DA 2022-11-30
ER

PT J
AU Campochiaro, PA
   Choy, DF
   Do, DV
   Hafiz, G
   Shah, SM
   Nguyen, QD
   Rubio, R
   Arron, JR
AF Campochiaro, Peter A.
   Choy, David F.
   Do, Diana V.
   Hafiz, Gulnar
   Shah, Syed Mahmood
   Nguyen, Quart D.
   Rubio, Roman
   Arron, Joseph R.
TI Monitoring Ocular Drug Therapy by Analysis of Aqueous Samples
SO OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MULTIPLEX BEAD ANALYSIS; RETINAL VEIN
   OCCLUSION; MACULAR EDEMA; DIABETIC-RETINOPATHY; VITREOUS LEVELS; HUMOR
   LEVELS; RANIBIZUMAB; NEOVASCULARIZATION; INTERLEUKIN-6
AB Objective: To assess the value of sampling aqueous humor for measurement of potential molecular targets and for pharmacokinetic analysis.
   Design: Substudy within the context of clinical trials.
   Participants: Forty patients with macular edema caused by central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO), 11 patients with diabetic macular edema (DME), and 8 patients with neovascular age-related macular degeneration (NVAMD).
   Methods: Assays for potential molecular targets were performed on aqueous samples from patients participating in drug studies (CRVO, BRVO, and DME) or patients receiving standard care (NVAMD). Ranibizumab levels were measured in patients with CRVO or BRVO after the first and second injections of ranibizumab.
   Main Outcome Measures: Aqueous levels of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, and ranibizumab.
   Results: Aqueous levels of VEGF were significantly higher in patients with DME than in patients with CRVO, which were significantly higher than those in patients with BRVO. Patients with NVAMD had aqueous VEGF levels in an intermediate range, significantly higher than those in patients with BRVO. One month after the second injection of ranibizumab, 27 of 39 patients with vein occlusions had no residual edema; mean aqueous levels of IL-6, IL-1 beta, and TNF-alpha were not greater in patients with residual edema; this provides a blueprint for definitive studies with larger cohorts. There was no significant difference in aqueous ranibizumab levels 1 month after the first injection of 0.5 mg versus injection of 0.3 mg, but 1 month after the second injection ranibizumab levels were significantly higher in eyes injected with 0.5 mg. There were substantial differences in levels among patients, but levels in the same patient at months 1 and 2 were highly correlated. No significant difference in aqueous ranibizumab levels was detected between phakic and pseudophakic patients who received the same dose.
   Conclusions: These data suggest that aqueous samples are useful for investigating potential involvement of molecular targets in various disease processes and for pharmacokinetic or pharmacodynamic studies.
   Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2009; 116:2158 -2164 (C) 2009 by the American Academy of Ophthalmology.
C1 [Campochiaro, Peter A.] Johns Hopkins Univ, Wilmer Eye Inst, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA.
   [Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
   [Choy, David F.; Rubio, Roman; Arron, Joseph R.] Genentech Inc, Ophthalm Med Immunol Tissue Growth & Repair Dept, San Francisco, CA 94080 USA.
   [Shah, Syed Mahmood] Univ Maryland Med Syst, Maryland Gen Hosp, Baltimore, MD USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins
   University; Roche Holding; Genentech; University System of Maryland;
   University of Maryland Baltimore
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ, Wilmer Eye Inst, Sch Med, Dept Ophthalmol, Maumenee 719,600 N Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhmi.edu
RI Shah, Syed/K-2672-2018
OI Arron, Joseph/0000-0001-7677-9979; Choy, David/0000-0003-1351-6113
FU Genentech, Inc.; Alimera, Inc.; CoMentis. Inc.; Regeneron, Inc.;
   NATIONAL EYE INSTITUTE [R01EY012609] Funding Source: NIH RePORTER
FX PAC and QDN have served as members of Expert Panels for Genentech, Inc.,
   without receiving an honorarium during the time of this study, but JHU
   recently negotiated a contract through which JHU receives compensation.
   PAC, QDN, and DVD receive grant funding from Genentech, Inc. PAC
   receives grant funding front Alimera, Inc., and CoMentis. Inc., and
   serves on the DSMC for the View 1 trial sponsored by Regeneron, Inc. QDN
   and DVD receive grant funding from Regeneron, Inc. These activites are
   being managed by the Conflict of Interest Committee of the Johns Hopkins
   University School of Medicine. DFC, RR, and JRA are employees of
   Genentech, Inc.
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NR 15
TC 55
Z9 60
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2009
VL 116
IS 11
BP 2158
EP 2164
DI 10.1016/j.ophtha.2009.04.038
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 512ZQ
UT WOS:000271291600017
PM 19700195
DA 2022-11-30
ER

PT J
AU Jonas, JB
AF Jonas, JB
TI Intravitreal triamcinolone acetonide for treatment of intraocular
   oedematous and neovascular diseases
SO ACTA OPHTHALMOLOGICA SCANDINAVICA
LA English
DT Review
DE intravitreal triamcinolone acetonide; diabetic macular oedema;
   age-related macular degeneration; intraocular pressure; intraocular
   steroids
ID CYSTOID MACULAR EDEMA; RETINAL VEIN OCCLUSION; PARS-PLANA VITRECTOMY;
   CENTRAL SEROUS CHORIORETINOPATHY; INTERNAL LIMITING MEMBRANE; CHOROIDAL
   NEOVASCULARIZATION; PHOTODYNAMIC THERAPY; CRYSTALLINE CORTISONE;
   PANRETINAL PHOTOCOAGULATION; ADJUNCTIVE TREATMENT
AB Intravitreal triamcinolone acetonide (IVTA) has increasingly been applied as treatment for various intraocular neovascular and oedematous diseases. Comparing the various diseases with respect to effect and side-effects of the treatment, the best response in terms of gain in visual acuity (VA) has been achieved for intraretinal oedematous diseases such as diffuse diabetic macular oedema, branch retinal vein occlusion, central retinal vein occlusion and pseudophakic cystoid macular oedema. In eyes with various types of non-infectious uveitis, including acute or chronic sympathetic ophthalmia and Adamantiadis-Behcet's disease, VA increased and the degree of intraocular inflammation decreased. Some studies have suggested that intravitreal triamcinolone may be useful as angiostatic therapy in eyes with iris neovascularization and proliferative ischaemic retinopathies. Intravitreal triamcinolone may possibly be helpful as adjunct therapy for exudative age-related macular degeneration (AMD), particularly in combination with photodynamic therapy. In eyes with chronic, therapy-resistant ocular hypotony, intravitreal triamcinolone can induce an increase in intraocular pressure (IOP) and may stabilize the eye. The complications of intravitreal triamcinolone therapy include: secondary ocular hypertension in about 40% of the eyes injected; medically uncontrollable high IOP leading to antiglaucomatous surgery in about 1-2% of the eyes; posterior subcapsular cataract and nuclear cataract leading to cataract surgery in about 15-20% of elderly patients within 1 year of injection; postoperative infectious endophthalmitis occurring at a rate of about one per 1000; non-infectious endophthalmitis, perhaps due to a reaction to the solvent agent, and pseudo-endophthalmitis with triamcinolone acetonide crystals appearing in the anterior chamber. Intravitreal triamcinolone injection can be combined with other intraocular surgeries, including cataract surgery, particularly in eyes with iris neovascularization. Cataract surgery performed some months after the injection does not show a markedly elevated complication rate. The injection may be repeated if the resultant benefits decrease after the initial IVTA injection. In non-vitrectomized eyes, the duration of the effect and side-effects of a single intravitreal injection of triamcinolone is about 6-9 months for a dosage of about 20 mg, and about 2-4 months for a dosage of 4 mg. So far, it has remained unclear whether the solvent agent should be removed, and if so, how.
C1 Heidelberg Univ, Fac Clin Med Mannheim, Dept Ophthalmol, Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg
RP Jonas, JB (通讯作者)，Heidelberg Univ, Fac Clin Med Mannheim, Dept Ophthalmol, Heidelberg, Germany.
EM Jost.Jonas@augen.ma.uni-heidelberg.de
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NR 235
TC 100
Z9 109
U1 1
U2 9
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1395-3907
J9 ACTA OPHTHALMOL SCAN
JI Acta Ophthalmol. Scand.
PD DEC
PY 2005
VL 83
IS 6
BP 645
EP 663
DI 10.1111/j.1600-0420.2005.00592.x
PG 19
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 987FL
UT WOS:000233503700003
PM 16396641
DA 2022-11-30
ER

PT J
AU Leung, IYF
   Sandstrom, MM
   Zucker, CL
   Neuringer, M
   Snodderly, DM
AF Leung, IYF
   Sandstrom, MM
   Zucker, CL
   Neuringer, M
   Snodderly, DM
TI Nutritional manipulation of primate retinas. IV. Effects of n-3 fatty
   acids, lutein, and zeaxanthin on S-cones and rods in the foveal region
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE macular pigment; carotenoid; lutein; zeaxanthin; essential fatty acids;
   unbiased counting; photoreceptor; xanthophyll
ID MACULAR PIGMENT DENSITY; AGE-RELATED MACULOPATHY; RHESUS-MONKEYS;
   DIETARY-FAT; PHOTORECEPTOR TOPOGRAPHY; LIGHT DAMAGE; FISH INTAKE;
   DEGENERATION; MACAQUE; CAROTENOIDS
AB Lutein and zeaxanthin are xanthophylls selectively accumulated by primate retinas that may protect the macula from age-related macular degeneration. In this project, we manipulated n-3 fatty acids, lutein and/or zeaxanthin levels in the diet and studied their possible outcome on S-cone and rod cell density in the foveal region. Rhesus monkeys (7-16 year, n = 17) were fed from birth xanthophyll-free semipurified diets with either adequate or low n-3 fatty acids. Five monkeys were supplemented with lutein and six with zeaxanthin for 6-24 months, while six remained xanthophyll-free until sacrifice. Retinas were embedded in methacrylate and serial 2 mu m sections were cut along the vertical meridian. Rod nuclei, and immunolabelled outer segments of S-cones and rods, were reconstructed and counted in an 8 mu m strip. The density profiles were compared with data from control monkeys (n = 7) fed a standard laboratory diet.
   S-cone density profiles were symmetrical along the vertical meridian and the densities decreased rapidly with retinal eccentricity. Rod densities were higher in the superior region than the inferior region in most of the control and experimental animals. Unlike the significant effects observed for retinal pigment epithelial cells of these same monkeys (Leung, I.Y-F., Sandstrom, M.M., Zucker, C.L., Neuringer, M., Snodderly, D.M., 2004. Nutritional manipulation of primate retinas. II. Effects of age, n-3 fatty acids, lutein, and zeaxanthin on retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 45, 3244-3256), neither xanthophyll supplementation nor low dietary n-3 fatty acids produced consistent effects on S-cone or rod density profiles of the experimental animals. However, monkeys low in n-3 fatty acids had increased variability of S-cone density in the fovea and low density of foveal rod outer segments. The high variability suggests that the photoreceptors of some animals were resistant to the nutritional manipulations, while others may have been affected. Thus, the photoreceptors appear less sensitive than the retinal pigment epithelium to these nutritional manipulations. However, it is possible that more consistent effects would emerge at a later age or after exposure to stressors such as high light levels. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Schepens Eye Res Inst, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
   Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA.
   Oregon Hlth & Sci Univ, Dept Med, Beaverton, OR 97006 USA.
   Oregon Hlth & Sci Univ, Dept Ophthalmol, Beaverton, OR 97006 USA.
   Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA.
   Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
C3 Harvard University; Schepens Eye Research Institute; Harvard University;
   Harvard Medical School; Boston University; Oregon Health & Science
   University; Oregon Health & Science University; Oregon Health & Science
   University; Oregon National Primate Research Center; Harvard University;
   Harvard Medical School
RP Leung, IYF (通讯作者)，Johns Hopkins Univ, Wilmer Eye Inst, 477 Woods Bldg,600 N Wolfe St, Baltimore, MD 21287 USA.
EM ivanleung@jhu.edu
OI Snodderly, Donald/0000-0002-3428-609X; Zucker,
   Charles/0000-0002-2373-7481
FU NATIONAL CENTER FOR RESEARCH RESOURCES [P51RR000163] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [P30EY003790] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY
   DISEASES [R01DK029930] Funding Source: NIH RePORTER; NCRR NIH HHS
   [RR-00163] Funding Source: Medline; NEI NIH HHS [P30 EY03790] Funding
   Source: Medline; NIDDK NIH HHS [DK-29930] Funding Source: Medline
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NR 61
TC 22
Z9 23
U1 1
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2005
VL 81
IS 5
BP 513
EP 529
DI 10.1016/j.exer.2005.03.009
PG 17
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 993MB
UT WOS:000233957100003
PM 15916761
DA 2022-11-30
ER

PT J
AU Hikichi, T
AF Hikichi, Taiichi
TI Sub-Tenon's capsule triamcinolone acetonide injection to prevent
   brolucizumab-associated intraocular inflammation
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Anti-vascular endothelial growth factor therapy; Brolucizumab;
   Intraocular inflammation; Neovascular age-related macular degeneration;
   Triamcinolone acetonide
ID DIABETIC MACULAR EDEMA; SUBTENON TRIAMCINOLONE; INTRAVITREAL;
   DEGENERATION
AB Purpose To investigate the efficacy of sub-Tenon's capsule triamcinolone acetonide (STTA) injections for preventing development of intraocular inflammation (IOI) related to intravitreal injection (IVI) of brolucizumab for neovascular age-related macular degeneration (nAMD).
   Methods Consecutive patients with nAMD treated with brolucizumab IVIs were studied retrospectively. All eyes treated with brolucizumab in the clinic were switched from another anti-vascular endothelial growth factor agent. After the fourth case of IOI related to brolucizumab IVI, all eyes treated with brolucizumab received a STTA injection. The patients were divided into two groups: brolucizumab alone and brolucizumab combined with a STTA injection.
   Results Forty-four eyes (44 patients) treated with at least one brolucizumab IVI were studied: 14 eyes received brolucizumab IVI alone and 30 eyes received the combination therapy. IOI related to brolucizumab IVIs developed in four (28.6%) of 14 eyes in the brolucizumab group; IOI was severe in one eye, moderate in two eyes, and mild in one eye according to the HAWK and HARRIER trial definition; IOI did not develop in the 30 eyes that received combination therapy, the difference of which reached significance (p = 0.012). Regarding combination therapy, the intraocular pressure in three (10%) eyes increased to 22 to about 26 mmHg after the STTA injection and returned to normal range within 2 months without medication; no cataracts developed during this short mean follow-up period follow-up period of 7.1 +/- 0.4 months.
   Conclusion The results indicated the possible preventative effect of a STTA injection on development of brolucizumab-associated IOI.
   Key messages
   Since the approval of brolucizumab, a number of post-marketing cases of severe visual acuity loss resulting from severe intraocular inflammation (IOI) and retinal vasculitis and/or retinal artery occlusion have been reported after brolucizumab injections;
   This preliminary paper revealed that a sub-Tenon's capsule triamcinolone acetonide (STTA) injection combined with a brolucizumab intravitreal injection (IVI) may prevent the IOI associated with brolucizumab;
   The combination therapy of a brolucizumab IVI with a STTA injection may be recommended for the selective patients such asa poor or no response to other anti-VEGF agents or for those who require frequent IVIs of anti VEGF agents, especially in the dominant eye.
C1 [Hikichi, Taiichi] Hikichi Eye Clin, Kita Ku, Kita 7 Nishi 5 7-1 Kita Sky Bldg 14 Floor, Sapporo, Hokkaido 0600807, Japan.
RP Hikichi, T (通讯作者)，Hikichi Eye Clin, Kita Ku, Kita 7 Nishi 5 7-1 Kita Sky Bldg 14 Floor, Sapporo, Hokkaido 0600807, Japan.
EM thikichi@hikichi-eye.jp
CR Abd El-Razik AH, 2014, MENOUFIA MED J, V27, P636
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NR 34
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD AUG
PY 2022
VL 260
IS 8
BP 2529
EP 2535
DI 10.1007/s00417-022-05611-y
EA MAR 2022
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3F5UF
UT WOS:000763202200001
PM 35235038
DA 2022-11-30
ER

PT J
AU Tang, D
   Dinh, H
   Almansour, H
   Burlutsky, G
   Bussing, J
   Eisenhauer, B
   Gopinath, B
   Flood, VM
   Saini, B
AF Tang, Diana
   Dinh, Helen
   Almansour, Hadi
   Burlutsky, George
   Bussing, Jocelyn
   Eisenhauer, Bronwyn
   Gopinath, Bamini
   Flood, Victoria M.
   Saini, Bandana
TI Evaluation of educational interventions on eye health for dietetic and
   pharmacy professions: a pre-post study
SO BMC MEDICAL EDUCATION
LA English
DT Article
DE Age-related macular degeneration; Eye health; Pharmacist; Dietitian
ID MACULAR DEGENERATION; SUPPLEMENTATION; INDEX
AB Background We piloted an educational intervention that aimed to enhance awareness about nutrition-age-related macular degeneration (AMD) links among practising and student dietitians then expanded the scope of this intervention to include general eye health, which was delivered to pharmacy students. Methods A pilot intervention was conducted in 2019 at the Dietitians Australia Conference (Gold Coast, Australia) where practising and student dietitians underwent a 2-hour small group educational workshop on nutrition and AMD links. Pre-post questionnaires were administered to participants, with voluntary completion of both questionnaires an indicator of consent to participate in the intervention. The primary intervention outcome was a change in AMD-related nutrition knowledge pre-post intervention. A larger intervention was then conducted at the University of Sydney (Sydney, Australia) where pharmacy students underwent a 4-hour educational module to improve general eye health knowledge, as well as student perceptions and attitudes towards a pharmacists' role in low vision care. Similarly, pre-post questionnaires were administered, with voluntary completion of both questionnaires an indicator of consent to participate in the intervention. The primary intervention outcomes were changes in total knowledge, total perception and total attitude scores pre-post intervention. Results (1) Among 10 accredited and 5 student dietitians, there was significant overall knowledge improvement (mean pre-post score: 7.07 +/- 1.94 vs. 10.8 +/- 1.01, p = 0.001) specifically around appropriate dietary advice, food sources of key AMD-related nutrients, and awareness of supplements. (2) Among 179 second-year pharmacy students enrolled in the 'Pharmacy Practice' Unit of Study (Bachelor of Pharmacy, University of Sydney), total eye health knowledge (6.25 +/- 1.93 vs. 6.64 +/- 2.0; p = 0.011) significantly improved, along with total perception scores (41.54 +/- 5.26 vs. 42.45 +/- 4.95; p = 0.004). Total attitude scores were not significantly different. Conclusions The pilot intervention improved relevant nutrition-AMD knowledge among practising/student dietitians. The modified intervention for pharmacy students also significantly improved general eye health knowledge as well as students' perception of a pharmacists' role in low vision care.
C1 [Tang, Diana; Burlutsky, George] Univ Sydney, Ctr Vis Res, Dept Ophthalmol, 176 Hawkesbury Rd, Sydney, NSW 2145, Australia.
   [Tang, Diana; Burlutsky, George] Univ Sydney, Westmead Inst Med Res, 176 Hawkesbury Rd, Sydney, NSW 2145, Australia.
   [Tang, Diana; Gopinath, Bamini] Macquarie Univ, Macquarie Univ Hearing, N Ryde, NSW, Australia.
   [Dinh, Helen; Almansour, Hadi; Bussing, Jocelyn; Saini, Bandana] Univ Sydney, Fac Med & Hlth, Sydney Pharm Sch, Camperdown, NSW, Australia.
   [Eisenhauer, Bronwyn] Food & Nutr Australia, Sydney, NSW, Australia.
   [Flood, Victoria M.] Univ Sydney, Fac Med & Hlth, Sydney Sch Hlth Sci, Sydney, NSW, Australia.
   [Flood, Victoria M.] Westmead Hosp, Western Sydney Local Hlth Dist, Westmead, NSW, Australia.
C3 University of Sydney; University of Sydney; Westmead Institute for
   Medical Research; Macquarie University; University of Sydney; University
   of Sydney; University of Sydney
RP Tang, D (通讯作者)，Univ Sydney, Ctr Vis Res, Dept Ophthalmol, 176 Hawkesbury Rd, Sydney, NSW 2145, Australia.; Tang, D (通讯作者)，Univ Sydney, Westmead Inst Med Res, 176 Hawkesbury Rd, Sydney, NSW 2145, Australia.; Tang, D (通讯作者)，Macquarie Univ, Macquarie Univ Hearing, N Ryde, NSW, Australia.
EM diana.tang@sydney.edu.au
OI Tang, Diana/0000-0003-2007-9054; Bussing, Jocelyn/0000-0003-3726-8062
CR Biggs J., 2011, TEACHING QUALITY LEA, V4, P86
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   United States Department of Agriculture (USDA), NAT NUTR DAT
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NR 28
TC 0
Z9 0
U1 2
U2 5
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1472-6920
J9 BMC MED EDUC
JI BMC Med. Educ.
PD SEP 7
PY 2021
VL 21
IS 1
AR 478
DI 10.1186/s12909-021-02905-3
PG 10
WC Education & Educational Research; Education, Scientific Disciplines
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Education & Educational Research
GA UM9OT
UT WOS:000693654500001
PM 34493275
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Cai, H
   Gong, J
   Abriola, L
   Hoyer, D
   Noggle, S
   Paull, D
   Del Priore, LV
   Fields, MA
AF Cai, Hui
   Gong, Jie
   Abriola, Laura
   Hoyer, Denton
   Noggle, Scott
   Paull, Daniel
   Del Priore, Lucian V.
   Fields, Mark A.
CA NYSCF Global Stem Cell Array Team
TI High-throughput screening identifies compounds that protect RPE cells
   from physiological stressors present in AMD
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelial cells;
   Induced pluripotent stem cells; Oxidative stress; Ciclopirox olamine
ID RETINAL-PIGMENT EPITHELIUM; MITOCHONDRIAL-DNA DAMAGE; PLURIPOTENT
   STEM-CELLS; B-INDUCED DAMAGE; OXIDATIVE STRESS; BUTYL HYDROPEROXIDE;
   CIGARETTE-SMOKING; INDUCED APOPTOSIS; BRUCHS MEMBRANE; CICLOPIROX
AB Dysfunction and eventual loss of retinal pigment epithelial (RPE) cells is a hallmark of atrophic age-related macular degeneration (AMD), and linked to oxidative and nitrosative damage. Herein, we use a high-throughput screen (HTS) to identify compounds that protect human RPE cells from oxidative stress-induced cell death and elucidate the possible mechanism of action. HTS was used to identify compounds that protect RPE cells from oxidative damage. We tested the identified compound(s) in models of RPE stress, including tert-butyl hydro peroxide (TBHP) exposure, ultraviolet-B (UV-B)-mediated light damage and nitrosative stress to the basement membrane using ARPE-19 cells, primary human RPE cells and induced-pluripotent stem cell (iPSC)-derived RPE cells from patients with AMD. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect gene expression of oxidative stress- and apoptosis-related genes and mitochondrial function was measured using a Seahorse XF96 analyzer to elucidate possible mechanisms of action. Five thousand and sixty-five compounds were screened, and of these, 12 compounds were active based on their ability to improve cell viability after exposure to TBHP. After chemical structure review, we identified ciclopirox olamine as a potent inhibitor of oxidative damage to RPE cells. Ciclopirox olamine increased cell viability in ARPE-19 cells treated with TBHP, UV-B light or on nitrite-modified extracellular matrix (ECM) by 1.68-fold, 1.54-fold and 4.3-fold, respectively (p < 0.01). Treatment with TBHP altered expression of genes related to oxidative stress and apoptosis, which was reversed by pretreatment with ciclopirox olamine. Ciclopirox olamine improved mitochondrial function in TBHP-exposed ARPE-19 cells and iPSC-derived RPE cells. Ciclopirox olamine protected primary human RPE cells and iPSC-derived RPE cells from the oxidative stress or damaged basement membrane. HTS of bioactive Food and Drug Administration (FDA)-approved libraries and follow-up studies can be used to identify small molecules (including ciclopirox olamine) that protect RPE cells exposed to various stressors associated with disease progression of AMD. This strategy can be used to identify potential compounds for treatment and prevention of AMD.
C1 [Cai, Hui; Gong, Jie; Del Priore, Lucian V.; Fields, Mark A.] Yale Sch Med, Dept Ophthalmol & Visual Sci, 300 George Sc,Suite 8100, New Haven, CT 06511 USA.
   [Abriola, Laura; Hoyer, Denton] Yale Ctr Mol Discovery, 600 West Campus Dr, West Haven, CT 06516 USA.
   [Noggle, Scott; Paull, Daniel; NYSCF Global Stem Cell Array Team] NYSCF, Res Inst, 619 West 54th St, New York, NY 10019 USA.
C3 Yale University; The New York Stem Cell Foundation
RP Fields, MA (通讯作者)，Yale Sch Med, Dept Ophthalmol & Visual Sci, 300 George Sc,Suite 8100, New Haven, CT 06511 USA.
EM mark.fields@yale.edu
OI Noggle, Scott/0000-0002-0374-2240
FU Research to Prevent Blindness (RPB), Inc., New York, NY, USA; Foundation
   Fighting Blindness (FFB), Columbia, MD, USA
FX This work has been supported in part by an unrestricted challenge award
   to the Yale Eye Center from Research to Prevent Blindness (RPB), Inc.,
   New York, NY, USA and the Foundation Fighting Blindness (FFB), Columbia,
   MD, USA.
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NR 76
TC 7
Z9 7
U1 2
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD AUG
PY 2019
VL 185
AR 107641
DI 10.1016/j.exer.2019.04.009
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IT8NU
UT WOS:000483140000019
PM 30980814
DA 2022-11-30
ER

PT J
AU Park, C
   Lee, H
   Hong, SH
   Kim, JH
   Park, SK
   Jeong, JW
   Kim, GY
   Hyun, JW
   Yun, SJ
   Kim, BW
   Kim, WJ
   Choi, YH
AF Park, Cheol
   Lee, Hyesook
   Hong, Su Hyun
   Kim, Jeong-Hwan
   Park, Seh-Kwang
   Jeong, Ji-Won
   Kim, Gi-Young
   Hyun, Jin Won
   Yun, Seok Joong
   Kim, Byung Woo
   Kim, Wun-Jae
   Choi, Yung Hyun
TI Protective effect of diphlorethohydroxycarmalol against oxidative
   stress-induced DNA damage and apoptosis in retinal pigment epithelial
   cells
SO CUTANEOUS AND OCULAR TOXICOLOGY
LA English
DT Article
DE Diphlorethohydroxycarmalol; ARPE19 retinal pigment epithelial cells;
   oxidative stress; DNA damage; apoptosis; age-related macular
   degeneration
ID ENERGY-METABOLISM; ARPE-19 CELLS; DEATH; DEGENERATION; RADIATION;
   MECHANISMS; EXPRESSION
AB Purpose: Reactive oxygen species (ROS) contribute to the onset and progression of disease pathogenesis in a variety of organs, including age-related macular degeneration (AMD). Diphlorethohydroxycarmalol (DPHC), a phlorotannin compound, is one of the major components of the brown alga Ishige okamurae Yendo, and has been shown to have strong antioxidant capacity. The purpose of this study was to evaluate the protective effects of DPHC against oxidative stress (hydrogen peroxide, H2O2)-induced DNA damage and apoptosis in cultured ARPE19 retinal pigment epithelial (RPE) cells. Materials and methods: Cell viability was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay. Intracellular ROS generation was measured by flow cytometer using 2 ',7 '-dichlorofluorescin diacetate. The magnitude of apoptosis was measured by flow cytometry using the annexin V/propidium iodide double staining. DNA damage was evaluated by DNA fragmentation assay, comet assay and 8-hydroxy-2 '-deoxyguanosine (8-OHdG) analysis. To observe the mitochondrial membrane potential, 5,5 ',6,6 '-tetrachloro-1,1 ',3,3 '-tetraethyl-imidacarbocyanine iodide staining was performed. In order to identify the underling mechanism of DPHC against H2O2-induced cellular alteration, we performed immune blotting. Results: The results of this study showed that the decreased survival rate brought about by H2O2 could be attributed to the induction of DNA damage and apoptosis accompanied by the increased production of ROS, which was remarkably reversed by DPHC. In addition, the loss of H2O2-induced mitochondrial membrane potential was significantly attenuated in the presence of DPHC. The inhibitory effect of DPHC on H2O2-induced apoptosis was associated with a reduced Bax/Bcl-2 ratio, the protection of the activation of caspase-9 and -3 and the inhibition of poly (ADP-ribose) polymerase cleavage, which was associated with the blockage of cytochrome c release to the cytoplasm. Conclusions: Our data proved that DPHC protects ARPE19 cells against H2O2-induced DNA damage and apoptosis by scavenging ROS and thus suppressing the mitochondrial-dependent apoptosis pathway. Therefore, this study suggests that DPHC has the therapeutic potential to prevent AMD by inhibiting oxidative stress-induced injury in RPE cells.
C1 [Park, Cheol] Dong Eui Univ, Dept Mol Biol, Coll Nat Sci, Busan, South Korea.
   [Lee, Hyesook; Hong, Su Hyun; Choi, Yung Hyun] Dong Eui Univ, Dept Biochem, Coll Korean Med, 52-57 Yangjeong Ro, Busan 47227, South Korea.
   [Lee, Hyesook; Hong, Su Hyun; Choi, Yung Hyun] Dong Eui Univ, Antiaging Res Ctr, Busan, South Korea.
   [Kim, Jeong-Hwan; Park, Seh-Kwang; Jeong, Ji-Won] BGN Eye Clin, BGN Care Co Ltd, Res Team, Busan, South Korea.
   [Kim, Gi-Young] Jeju Natl Univ, Dept Marine Life Sci, Sch Marine Biomed Sci, Jeju, South Korea.
   [Hyun, Jin Won] Jeju Natl Univ, Dept Biochem, Sch Med, Jeju, South Korea.
   [Yun, Seok Joong; Kim, Wun-Jae] Chungbuk Natl Univ, Dept Urol, Coll Med, 776 1 Sunhwan Ro, Cheongju 28644, South Korea.
   [Kim, Byung Woo] Dong Eui Univ, Biopharmaceut Engn Major, Div Appl Bioengn, Coll Engn, Busan, South Korea.
C3 Dong-Eui University; Dong-Eui University; Dong-Eui University; Jeju
   National University; Jeju National University; Chungbuk National
   University; Dong-Eui University
RP Choi, YH (通讯作者)，Dong Eui Univ, Dept Biochem, Coll Korean Med, 52-57 Yangjeong Ro, Busan 47227, South Korea.; Kim, WJ (通讯作者)，Chungbuk Natl Univ, Dept Urol, Coll Med, 776 1 Sunhwan Ro, Cheongju 28644, South Korea.; Kim, WJ (通讯作者)，Chungbuk Natl Univ, Inst Tumor Res, 776 1 Sunhwan Ro, Cheongju 28644, South Korea.
EM wjkim@chungbuk.ac.kr; choiyh@deu.ac.kr
OI Kim, Jeong-Hwan/0000-0003-2219-5649; Lee, Hyesook/0000-0003-3546-9370;
   Jeong, Ji-Won/0000-0001-9182-0132
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NR 58
TC 20
Z9 20
U1 1
U2 10
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1556-9527
EI 1556-9535
J9 CUTAN OCUL TOXICOL
JI Cutan. Ocul. Toxicol.
PD JUL 3
PY 2019
VL 38
IS 3
BP 298
EP 308
DI 10.1080/15569527.2019.1613425
PG 11
WC Ophthalmology; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Toxicology
GA IR6BF
UT WOS:000481523800015
PM 31060395
DA 2022-11-30
ER

PT J
AU Hsu, HJ
   Huang, RF
   Kao, TH
   Inbaraj, BS
   Chen, BH
AF Hsu, H. J.
   Huang, R. F.
   Kao, T. H.
   Inbaraj, B. S.
   Chen, B. H.
TI Preparation of carotenoid extracts and nanoemulsions from Lycium
   barbarum L. and their effects on growth of HT-29 colon cancer cells
SO NANOTECHNOLOGY
LA English
DT Article
DE Lycium barbarum L.; carotenoid nanoemulsion; colon cancer cell HT-29;
   cell cycle
ID PROSTATE-CANCER; DERMAL DELIVERY; DRUG-DELIVERY; APOPTOSIS; INHIBITION;
   ZEAXANTHIN; STABILITY; LINNAEUS; ARREST; LUTEIN
AB Lycium barbarum L., a traditional Chinese herb widely used in Asian countries, has been demonstrated to be protective against chronic diseases such as age-related macular degeneration. The objectives of this study were to determine the carotenoid content in L. barbarum by highperformance liquid chromatography-mass spectrometry, followed by preparation of a carotenoid nanoemulsion to evaluate the mechanism. of inhibition on HT-29 colon cancer cells. The highest extraction yield of carotenoids was attained by employing a solvent system of hexane-ethanolacetone (1: 1: 1, v/v/v). Nine carotenoids, including neoxanthin (4.47 mu g g(-1)), all-transzeaxanthin and its cis-isomers (1666.3 mu g g-1), all-trans-a-cryptoxanthin (51.69 mu g g(-1)), alltrans- a-carotene and its cis-isomers (20.11 mu g g(-1)), were separated within 45 min and quantified using a YMC C-30 column and a gradient mobile phase of methanol-water (9: 1, v/v) (A) and methylene chloride (B). A highly stable carotenoid nanoemulsion composed of Capryol (TM) 90, Transcutol (R) HP, Tween 80 and deionized water was prepared with a mean particle size of 15.1 nm. Characterization of zeaxanthin standard, blank nanoemulsion, carotenoid extract and carotenoid nanoemulsion by differential scanning calorimetry curves and Fourier transform infrared spectra revealed a good dispersion of zeaxanthin-dominated carotenoid extract with no significant chemical change after incorporation into nanoemulsion. The in vitro release kinetic study showed a higher release profile at pH 5.2 than at physiological pH 7.4, suggesting a rapid release of carotenoids in the acidic environment (pH 4.5-6.5) characteristic of tumors. Both the carotenoid nanoemulsion and the extract were effective at inhibiting growth of HT-29. colon cancer cells, with an IC50 of 4.5 and 4.9 mu g ml(-1), respectively. Also, both treatments could upregulate p53 and p21 expression and down-regulate CDK2, CDK1, cyclin A and cyclin B expression and arrest the cell cycle at G(2)/M. The study may form a basis for further exploration of L. barbarum nanoemulsion in cancer treatment.
C1 [Hsu, H. J.; Kao, T. H.; Inbaraj, B. S.; Chen, B. H.] Fu Jen Catholic Univ, Dept Food Sci, New Taipei 242, Taiwan.
   [Huang, R. F.] Fu Jen Catholic Univ, Dept Nutr Sci, New Taipei 242, Taiwan.
C3 Fu Jen Catholic University; Fu Jen Catholic University
RP Chen, BH (通讯作者)，Fu Jen Catholic Univ, Dept Food Sci, New Taipei 242, Taiwan.
EM 002622@mail.fju.edu.tw
RI Stephen Inbaraj, Baskaran/AEM-6809-2022; Inbaraj, Baskaran
   Stephen/AAW-2077-2021; Inbaraj, Baskaran Stephen/Q-9419-2019
OI Stephen Inbaraj, Baskaran/0000-0003-4301-7614; Inbaraj, Baskaran
   Stephen/0000-0003-4301-7614; 
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NR 58
TC 28
Z9 29
U1 3
U2 58
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0957-4484
EI 1361-6528
J9 NANOTECHNOLOGY
JI Nanotechnology
PD MAR 31
PY 2017
VL 28
IS 13
AR 135103
DI 10.1088/1361-6528/aa5e86
PG 16
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
   Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics; Materials Science; Physics
GA EN7OK
UT WOS:000396191900001
PM 28266352
DA 2022-11-30
ER

PT J
AU Acharya, UR
   Mookiah, MRK
   Koh, JEW
   Tan, JH
   Bhandary, SV
   Rao, AK
   Fujita, H
   Hagiwara, Y
   Chua, CK
   Laude, A
AF Acharya, U. Rajendra
   Mookiah, Muthu Rama Krishnan
   Koh, Joel E. W.
   Tan, Jen Hong
   Bhandary, Sulatha V.
   Rao, A. Krishna
   Fujita, Hamido
   Hagiwara, Yuki
   Chua, Chua Kuang
   Laude, Augustinus
TI Automated screening system for retinal health using bi-dimensional
   empirical mode decomposition and integrated index
SO COMPUTERS IN BIOLOGY AND MEDICINE
LA English
DT Article
DE Retina; Fundus imaging; Posterior segment eye diseases; Bi-dimensional
   empirical mode decomposition; Energy; Entropy; Computer aided diagnosis
ID DECISION-SUPPORT-SYSTEM; DISCRETE WAVELET TRANSFORM; MACULAR
   DEGENERATION; DIABETIC-RETINOPATHY; VISUAL IMPAIRMENT; DIAGNOSIS;
   FEATURES; CLASSIFICATION; EXTRACTION; ENTROPY
AB Posterior Segment Eye Diseases (PSED) namely Diabetic Retinopathy (DR), glaucoma and Age-related Macular Degeneration (AMD) are the prime causes of vision loss globally. Vision loss can be prevented, if these diseases are detected at an early stage. Structural abnormalities such as changes in cup-to-disc ratio, Hard Exudates (HE), drusen, Microaneurysms (MA), Cotton Wool Spots (CWS), Haemorrhages (HA), Geographic Atrophy (GA) and Choroidal Neovascularization (CNV) in PSED can be identified by manual examination of fundus images by clinicians. However, manual screening is labour-intensive, tiresome and time consuming. Hence, there is a need to automate the eye screening. In this work Bi-dimensional Empirical Mode Decomposition (BEMD) technique is used to decompose fundus images into 2D Intrinsic Mode Functions (IMFs) to capture variations in the pixels due to morphological changes. Further, various entropy namely Renyi, Fuzzy, Shannon, Vajda, Kapur and Yager and energy features are extracted from IMFs. These extracted features are ranked using Chernoff Bound and Bhattacharyya Distance (CBBD), Kullback-Leibler Divergence (KLD), Fuzzy-minimum Redundancy Maximum Relevance (FmRMR), Wilcoxon, Receiver Operating Characteristics Curve (ROC) and t-test methods. Further, these ranked features are fed to Support Vector Machine (SVM) classifier to classify normal and abnormal (DR, AMD and glaucoma) classes. The performance of the proposed eye screening system is evaluated using 800 (Normal=400 and Abnormal=400) digital fundus images and 10-fold cross validation method. Our proposed system automatically identifies normal and abnormal classes with an average accuracy of 88.63%, sensitivity of 86.25% and specificity of 91% using 17 optimal features ranked using CBBD and SVM-Radial Basis Function (RBF) classifier. Moreover, a novel Retinal Risk Index (RRI) is developed using two significant features to distinguish two classes using single number. Such a system helps to reduce eye screening time in polyclinics or community-based mass screening. They will refer the patients to main hospitals only if the diagnosis belong to the abnormal class. Hence, the main hospitals will not be unnecessarily crowded and doctors can devote their time for other urgent cases. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Acharya, U. Rajendra; Mookiah, Muthu Rama Krishnan; Koh, Joel E. W.; Tan, Jen Hong; Hagiwara, Yuki; Chua, Chua Kuang] Ngee Ann Polytech, Dept Elect & Comp Engn, Singapore 599489, Singapore.
   [Acharya, U. Rajendra] SIM Univ, Sch Sci & Technol, Dept Biomed Engn, Singapore 599491, Singapore.
   [Acharya, U. Rajendra] Univ Malaya, Fac Engn, Dept Biomed Engn, Kuala Lumpur 50603, Malaysia.
   [Bhandary, Sulatha V.; Rao, A. Krishna] Kasturba Med Coll & Hosp, Dept Ophthalmol, Manipal 576104, India.
   [Fujita, Hamido] Iwate Prefectural Univ, Fac Software & Informat Sci, Takizawa, Iwate 0200693, Japan.
   [Laude, Augustinus] Tan Tock Seng Hosp, Inst Eye, Natl Healthcare Grp, Singapore 308433, Singapore.
C3 Singapore University of Social Sciences (SUSS); Universiti Malaya;
   Manipal Academy of Higher Education (MAHE); Kasturba Medical College,
   Manipal; Iwate Prefectural University; Tan Tock Seng Hospital
RP Mookiah, MRK (通讯作者)，Ngee Ann Polytech, Dept Elect & Comp Engn, Singapore 599489, Singapore.
EM mkm2@np.edu.sg
RI Mookiah, Muthu Rama Krishnan/G-4033-2011; Tan, Jen Hong/ABE-6525-2020;
   Tan, Jenhong/AAD-3664-2020; Acharya, Rajendra U/E-3791-2010; Fujita,
   Hamido/D-6249-2012
OI Mookiah, Muthu Rama Krishnan/0000-0001-6437-1482; Acharya, Rajendra
   U/0000-0003-2689-8552; Fujita, Hamido/0000-0001-5256-210X; Bhandary,
   Sulatha/0000-0002-3150-707X; Hagiwara, Yuki/0000-0002-5418-738X
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NR 71
TC 50
Z9 50
U1 0
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0010-4825
EI 1879-0534
J9 COMPUT BIOL MED
JI Comput. Biol. Med.
PD AUG 1
PY 2016
VL 75
BP 54
EP 62
DI 10.1016/j.compbiomed.2016.04.015
PG 9
WC Biology; Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Computer Science;
   Engineering; Mathematical & Computational Biology
GA DS2OJ
UT WOS:000380623100007
PM 27253617
DA 2022-11-30
ER

PT J
AU Sloan, FA
   Yashkin, AP
   Chen, YQ
AF Sloan, Frank A.
   Yashkin, Arseniy P.
   Chen, Yiqun
TI Gaps in Receipt of Regular Eye Examinations among Medicare Beneficiaries
   Diagnosed with Diabetes or Chronic Eye Diseases
SO OPHTHALMOLOGY
LA English
DT Article
ID CARE UTILIZATION; UNITED-STATES; VISION IMPAIRMENT; MANAGED CARE;
   OLDER-ADULTS; US ADULTS; INSURANCE; GLAUCOMA; HEALTH; AGE
AB Objective: To examine a wide range of factors associated with regular eye examination receipt among elderly individuals diagnosed with glaucoma, age-related macular degeneration, or diabetes mellitus (DM).
   Design: Retrospective analysis of Medicare claims linked to survey data from the Health and Retirement Study (HRS).
   Participants: The sample consisted of 2151 Medicare beneficiaries who responded to the HRS.
   Methods: Medicare beneficiaries with >= 1 of the 3 study diagnoses were identified by diagnosis codes and merged with survey information. The same individuals were followed for 5 years divided into four 15-month periods. Predictors of the number of periods with an eye examination evaluated were beneficiary demographic characteristics, income, health, cognitive and physical function, health behaviors, subjective beliefs about longevity, the length of the individual's financial planning horizon, supplemental health insurance coverage, eye disease diagnoses, and low vision/blindness at baseline. We performed logit analysis of the number of 15-month periods in which beneficiaries received an eye examination.
   Main Outcome Measures: The primary outcome measure was the number of 15-month periods with an eye examination.
   Results: One third of beneficiaries with the study's chronic diseases saw an eye care provider in all 4 followup periods despite having Medicare. One quarter only obtained an eye examination at most during 1 of the four 15-month follow-up periods. Among the 3 groups of patients studied, utilization was particularly low for persons with diagnosed DM and no eye complications. Age, marriage, education, and a higher score on the Charlson index were associated with more periods with an eye examination. Male gender, being limited in instrumental activities of daily living at baseline, distance to the nearest ophthalmologist, and low cognitive function were associated with a reduction in frequency of eye examinations.
   Conclusions: Rates of eye examinations for elderly persons with DM or frequently occurring eye diseases, especially for DM, remain far below recommended levels in a nationally representative sample of persons with health insurance coverage. Several factors, including limited physical and cognitive function and greater distance to an ophthalmologist, but not health insurance coverage, account for variation in regular use. (C) 2014 by the American Academy of Ophthalmology.
C1 [Sloan, Frank A.; Yashkin, Arseniy P.; Chen, Yiqun] Duke Univ, Dept Econ, Durham, NC 27708 USA.
C3 Duke University
RP Sloan, FA (通讯作者)，Duke Univ, Dept Econ, 213 Social Sci Bldg,Box 90097, Durham, NC 27708 USA.
EM fsloan@duke.edu
RI Yashkin, Arseniy/AAT-4613-2020
FU National Institute on Aging (NIA) [R01-AG017473]; NATIONAL INSTITUTE ON
   AGING [R01AG017473] Funding Source: NIH RePORTER
FX Research for this article was supported in part by the National
   Institute on Aging (NIA) to Duke University (R01-AG017473). The funding
   organizations had no role in the design or conduct of this research.
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NR 41
TC 35
Z9 35
U1 1
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD DEC
PY 2014
VL 121
IS 12
BP 2452
EP 2460
DI 10.1016/j.ophtha.2014.07.020
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA AU3JR
UT WOS:000345509500030
PM 25208856
OA Green Accepted, Green Submitted
DA 2022-11-30
ER

PT J
AU Guha, S
   Coffey, EE
   Lu, WN
   Lim, JC
   Beckel, JM
   Laties, AM
   Boesze-Battaglia, K
   Mitchell, CH
AF Guha, Sonia
   Coffey, Erin E.
   Lu, Wennan
   Lim, Jason C.
   Beckel, Jonathan M.
   Laties, Alan M.
   Boesze-Battaglia, Kathleen
   Mitchell, Claire H.
TI Approaches for detecting lysosomal alkalinization and impaired
   degradation in fresh and cultured RPE cells: Evidence for a role in
   retinal degenerations
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retinal pigmented epithelium; lysosome; autophagy; Alzheimer's disease;
   lipofuscin; cathepsin D; aging
ID PIGMENTED EPITHELIAL-CELLS; LIPOFUSCIN FLUOROPHORE;
   RHEUMATOID-ARTHRITIS; OCULAR COMPLICATIONS; ALZHEIMERS-DISEASE; OUTER
   SEGMENTS; ATP RELEASE; CHLOROQUINE; AUTOPHAGY; PH
AB Lysosomes contribute to a multitude of cellular processes, and the pH of the lysosomal lumen plays a central mechanistic role in many of these functions. In addition to controlling the rate of enzymatic degradation for material delivered through autophagic or phagocytotic pathways, lysosomal pH regulates events such as lysosomal fusion with autophagosomes and the release of lysosomal calcium into the cytoplasm. Disruption of either the steady state lysosomal pH or of the regulated manipulations to lysosomal pH may be pathological. For example, chloroquine elevates the lysosomal pH of retinal pigmented epithelial (RPE) cells and triggers a retinopathy characterized by the accumulation of lipofuscin-like material in both humans and animals. Compensatory responses to restore lysosomal pH are observed; new data illustrate that chronic chloroquine treatment increases mRNA expression of the lysosomal/autophagy master transcription factor TcFEB and of the vesicular proton pump vHATPase in the RPE/choroid of mice. An elevated lysosomal pH with upregulation of TcFEB and vHATPase resembles the pathology in fibroblasts of patients with mutant presenilin 1 (PSI), suggesting a common link between age-related macular degeneration (AMD) and Alzheimer's disease. While the absolute rise in pH is often small in these disorders, elevations of only a few tenths of a pH unit can have a major impact on both lysosomal function and the accumulation of waste over decades. Accurate measurement of lysosomal pH can be complex, and imprecise measurements have clouded the field. Protocols to optimize pH measurement from fresh and cultured cells are discussed, and indirect measurements to confirm changes in lysosomal pH and degradative capacity are addressed. The ability of reacidifying treatments to restore degradative function confirms the central role of lysosomal pH in these disorders and identifies potential approaches to treat diseases of lysosomal accumulation like AMD and Alzheimer's disease. In summary, various approaches to determine lysosomal pH in fresh and cultured cells, as well as the potential to restore pH levels to an optimal range, can help identify and repair pathologies associated with lysosomal defects in RPE cells and perhaps also suggest new approaches to treat lysosomal storage diseases throughout the body. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Guha, Sonia; Coffey, Erin E.; Lu, Wennan; Lim, Jason C.; Beckel, Jonathan M.; Mitchell, Claire H.] Univ Penn, Dept Anat, Philadelphia, PA 19104 USA.
   [Guha, Sonia; Coffey, Erin E.; Lu, Wennan; Lim, Jason C.; Beckel, Jonathan M.; Mitchell, Claire H.] Univ Penn, Dept Cell Biol, Philadelphia, PA 19104 USA.
   [Mitchell, Claire H.] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA.
   [Laties, Alan M.] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Boesze-Battaglia, Kathleen] Univ Penn, Dept Biochem, Philadelphia, PA 19104 USA.
   [Guha, Sonia] Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA USA.
   [Beckel, Jonathan M.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15260 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of
   Pennsylvania; University of Pennsylvania; University of Pennsylvania;
   University of California System; University of California Los Angeles;
   Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh
RP Mitchell, CH (通讯作者)，Univ Penn, Dept Anat & Cell Biol, 440 Levy Bldg,240 S 40th St, Philadelphia, PA 19104 USA.
EM chm@exchange.upenn.edu
RI Beckel, Jonathan/A-6758-2008
OI Beckel, Jonathan/0000-0003-1390-2292; Guha, Sonia/0000-0002-7585-8381
FU NIH [R01EY013434, R01EY015537, R01EY10420, P30EY001583, T32GM075770];
   Paul and Evanina Bell Mackall Foundation Trust; Jody Sack Fund; NATIONAL
   EYE INSTITUTE [P30EY001583, R01EY010420, R01EY013434, R01EY015537]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL
   SCIENCES [T32GM075770] Funding Source: NIH RePORTER
FX The authors would like to thank Ji Liu for help with the early studies
   that went into this work. This work is supported by grants from the NIH
   R01EY013434 (CHM), R01EY015537 (CHM), R01EY10420 (KBB), P30EY001583 (CHM
   & KBB), T32GM075770 (JMB), Research to Prevent Blindness (AML), the Paul
   and Evanina Bell Mackall Foundation Trust (AML) and the Jody Sack Fund
   (WL).
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NR 80
TC 55
Z9 56
U1 0
U2 20
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD SEP
PY 2014
VL 126
SI SI
BP 68
EP 76
DI 10.1016/j.exer.2014.05.013
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AO2CA
UT WOS:000341121900009
PM 25152362
OA Green Accepted, Green Published
DA 2022-11-30
ER

PT J
AU Koprowski, R
   Rzendkowski, M
   Wrobel, Z
AF Koprowski, Robert
   Rzendkowski, Marek
   Wrobel, Zygmunt
TI Automatic method of analysis of OCT images in assessing the severity
   degree of glaucoma and the visual field loss
SO BIOMEDICAL ENGINEERING ONLINE
LA English
DT Article
DE Image processing; Measurement automation; OCT; Segmentation; BGA;
   Biomorphological glaucoma advancement; Glaucoma
ID RETINAL LAYER SEGMENTATION; COHERENCE; THICKNESS; IDENTIFICATION
AB Introduction: In many practical aspects of ophthalmology, it is necessary to assess the severity degree of glaucoma in cases where, for various reasons, it is impossible to perform a visual field test - static perimetry. These are cases in which the visual field test result is not reliable, e. g. advanced AMD (Age-related Macular Degeneration). In these cases, there is a need to determine the severity of glaucoma, mainly on the basis of optic nerve head (ONH) and retinal nerve fibre layer (RNFL) structure. OCT is one of the diagnostic methods capable of analysing changes in both, ONH and RNFL in glaucoma.
   Material and method: OCT images of the eye fundus of 55 patients (110 eyes) were obtained from the SOCT Copernicus (Optopol Tech. SA, Zawiercie, Poland). The authors proposed a new method for automatic determination of the RNFL (retinal nerve fibre layer) and other parameters using: mathematical morphology and profiled segmentation based on morphometric information of the eye fundus. A quantitative ratio of the quality of the optic disk and RNFL - BGA (biomorphological glaucoma advancement) was also proposed. The obtained results were compared with the results obtained from a static perimeter.
   Results: Correlations between the known parameters of the optic disk as well as those suggested by the authors and the results obtained from static perimetry were calculated. The result of correlation with the static perimetry was 0.78 for the existing methods of image analysis and 0.86 for the proposed method. Practical usefulness of the proposed ratio BGA and the impact of the three most important features on the result were assessed. The following results of correlation for the three proposed classes were obtained: cup/disk diameter 0.84, disk diameter 0.97 and the RNFL 1.0. Thus, analysis of the supposed visual field result in the case of glaucoma is possible based only on OCT images of the eye fundus.
   Conclusions: The calculations and analyses performed with the proposed algorithm and BGA ratio confirm that it is possible to calculate supposed mean defect ( MD) of the visual field test based on OCT images of the eye fundus.
C1 [Koprowski, Robert; Wrobel, Zygmunt] Univ Silesia, Inst Comp Sci, Fac Comp Sci & Mat Sci, Dept Biomed Comp Syst, PL-41200 Sosnowiec, Poland.
C3 University of Silesia in Katowice
RP Koprowski, R (通讯作者)，Univ Silesia, Inst Comp Sci, Fac Comp Sci & Mat Sci, Dept Biomed Comp Syst, Ul Bedzinska 39, PL-41200 Sosnowiec, Poland.
EM robert.koprowski@us.edu.pl
OI Koprowski, Robert/0000-0001-7015-7984; Wrobel,
   Zygmunt/0000-0002-0636-1769
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NR 31
TC 16
Z9 17
U1 0
U2 12
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1475-925X
J9 BIOMED ENG ONLINE
JI Biomed. Eng. Online
PD FEB 14
PY 2014
VL 13
AR 16
DI 10.1186/1475-925X-13-16
PG 17
WC Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA AF0AD
UT WOS:000334372900001
PM 24528923
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Perlee, LT
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   Gehrs, K
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   Paladino, T
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   Hageman, GS
AF Perlee, Lorah T.
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   Heier, Jeffrey S.
   Csaky, Karl
   Allikmets, Rando
   Oeth, Paul
   Paladino, Toni
   Farkas, Daniel H.
   Rawlings, P. Lyle
   Hageman, Gregory S.
TI Inclusion of Genotype with Fundus Phenotype Improves Accuracy of
   Predicting Choroidal Neovascularization and Geographic Atrophy
SO OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; SEVERITY SCALE; EYE DISEASE; RISK; MODELS; AREDS;
   DELAY; SUSCEPTIBILITY; PROGRESSION; HAPLOTYPE
AB Purpose: The accuracy of predicting conversion from early-stage age-related macular degeneration (AMD) to the advanced stages of choroidal neovascularization (CNV) or geographic atrophy (GA) was evaluated to determine whether inclusion of clinically relevant genetic markers improved accuracy beyond prediction using phenotypic risk factors alone.
   Design: Cohort study.
   Participants: White, non-Hispanic subjects participating in the Age-Related Eye Disease Study (AREDS) sponsored by the National Eye Institute consented to provide a genetic specimen. Of 2415 DNA specimens available, 940 were from disease-free subjects and 1475 were from subjects with early or intermediate AMD.
   Methods: DNA specimens from study subjects were genotyped for 14 single nucleotide polymorphisms (SNPs) in genes shown previously to associate with CNV: ARMS2, CFH, C3, C2, FB, CFHR4, CFHR5, and F13B. Clinical demographics and established disease associations, including age, sex, smoking status, body mass index (BMI), AREDS treatment category, and educational level, were evaluated. Four multivariate logistic models (phenotype; genotype; phenotype + genotype; and phenotype + genotype + demographic + environmental factors) were tested using 2 end points (CNV, GA). Models were fitted using Cox proportional hazards regression to use time-to-disease onset data.
   Main Outcome Measures: Brier score (measure of accuracy) was used to identify the model with the lowest prediction error in the training set. The most accurate model was subjected to independent statistical validation, and final model performance was described using area under the receiver operator curve (AUC) or C-statistic.
   Results: The CNV prediction models that combined genotype with phenotype with or without age and smoking revealed superior performance (C-statistic = 0.96) compared with the phenotype model based on the simplified severity scale and the presence of CNV in the nonstudy eye (C-statistic = 0.89; P<0.01). For GA, the model that combined genotype with phenotype demonstrated the highest performance (AUC = 0.94). Smoking status and ARMS2 genotype had less of an impact on the prediction of GA compared with CNV.
   Conclusions: Inclusion of genotype assessment improves CNV prediction beyond that achievable with phenotype alone and may improve patient management. Separate assessments should be used to predict progression to CNV and GA because genetic markers and smoking status do not equally predict both end points. (c) 2013 by the American Academy of Ophthalmology.
C1 [Perlee, Lorah T.] Sequenom Inc, San Diego, CA 92121 USA.
   [Bansal, Aruna T.] Acclarogen Ltd, Cambridge, England.
   [Gehrs, Karen] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
   [Heier, Jeffrey S.] Ophthalm Consultants Boston, Boston, MA USA.
   [Csaky, Karl] Texas Retina Associates, Dallas, TX USA.
   [Allikmets, Rando] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
   [Allikmets, Rando] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA.
   [Oeth, Paul; Paladino, Toni] Sequenom Ctr Mol Med LLC SCMM, San Diego, CA USA.
   [Farkas, Daniel H.; Rawlings, P. Lyle] Sequenom Ctr Mol Med LLC SCMM, Grand Rapids, MI USA.
   [Hageman, Gregory S.] Univ Utah, Dept Ophthalmol & Visual Sci, John A Moran Eye Ctr, Salt Lake City, UT USA.
C3 Sequenom; University of Iowa; Ophthalmic Consultants of Boston; Columbia
   University; Columbia University; Sequenom; Sequenom; Utah System of
   Higher Education; University of Utah
RP Perlee, LT (通讯作者)，Sequenom Inc, 3595 John Hopkins Dr, San Diego, CA 92121 USA.
EM lperlee@sequenom.com
RI Mitchell, Paul/P-1498-2014; Allikmets, Rando/ABD-4533-2021
OI Gehrs, Karen/0000-0003-4510-9678
FU Sequenom Center for Molecular Medicine, San Diego, California; National
   Eye Institute, National Institutes of Health, Bethesda, Maryland
   [N01-EY-0-2127]; NATIONAL EYE INSTITUTE [P30EY014800, N01EY002127,
   R01EY013435] Funding Source: NIH RePORTER
FX Sequenom Center for Molecular Medicine, San Diego, California. The
   sponsor participated in designing and conducting the study; collecting,
   managing, analyzing, and interpreting the data; and preparing and
   reviewing the manuscript. This study was conducted in compliance with
   the Coriell Cell Repositories Institutional Review Board, in accordance
   with Department of Health and Human Services (45 CFR Part 46). The
   dataset used for the analysis contained in this manuscript was obtained
   from the National Eye Institute AREDS Genetic Repository. Funding
   support for AREDS was provided by the National Eye Institute Grant
   N01-EY-0-2127, National Institutes of Health, Bethesda, Maryland.
CR AMD Alliance International, BAS FACTS AMD
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NR 24
TC 35
Z9 35
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD SEP
PY 2013
VL 120
IS 9
BP 1880
EP 1892
DI 10.1016/j.ophtha.2013.02.007
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 213HG
UT WOS:000324045800043
PM 23523162
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Glenn, JV
   Beattie, JR
   Barrett, L
   Frizzell, N
   Thorpe, SR
   Boulton, ME
   McGarvey, JJ
   Stitt, AW
AF Glenn, Josephine V.
   Beattie, J. Renwick
   Barrett, Lindsay
   Frizzell, Norma
   Thorpe, Suzanne R.
   Boulton, Mike E.
   McGarvey, John J.
   Stitt, Alan W.
TI Confocal Raman microscopy can quantify advanced glycation end product
   (AGE) modifications in Bruch's membrane leading to accurate,
   nondestructive prediction of ocular aging
SO FASEB JOURNAL
LA English
DT Article
DE RPE; Raman spectroscopy
ID MAILLARD REACTION-PRODUCTS; RETINAL-PIGMENT EPITHELIUM; HUMAN
   ARTICULAR-CARTILAGE; MACULAR DEGENERATION; SKIN COLLAGEN;
   DIABETIC-RETINOPATHY; LENS CRYSTALLINS; PROTEINS; ACCUMULATION;
   N-EPSILON-(CARBOXYMETHYL)LYSINE
AB The modification of proteins by nonenzymatic glycation leading to accumulation of advanced glycation end products ( AGEs) is a well-established phenomenon of aging. In the eyes of elderly patients, these adducts have been observed in retinal pigment epithelium (RPE), particularly within the underlying pentalaminar substrate known as Bruch's membrane. AGEs have also been localized to age-related subcellular deposits ( drusen and basal laminar deposits) and are thought to play a pathogenic role in progression of the major sight-threatening condition known as age-related macular degeneration (AMD). The current study has quantified AGEs in Bruch's membrane from postmortem eyes and established age-related correlations. In particular, we investigated the potential of confocal Raman microscopy to identify and quantify AGEs in Bruch's membrane in a nondestructive, analytical fashion. Bruch's membrane and the innermost layers of the underlying choroid (BM-Ch) were dissected from fresh postmortem eye-cups (n = 56). AGE adducts were quantified from homogenized tissue using reverse-phase HPLC and GC/MS in combination with immunohistochemistry. For parallel Raman analysis, BM-Ch was flat-mounted on slides and evaluated using a Raman confocal microscope and spectra analyzed by a range of statistical approaches. Quantitative analysis showed that the AGEs pentosidine, carboxymethyllysine (CML), and carboxyethyllysine (CEL) occurred at significantly higher levels in BM-Ch with age (P<0.05-0.01). Defined Raman spectral "fingerprints" were identified for various AGEs and these were observed in the clinical samples using confocal Raman microscopy. The Raman data set successfully modeled AGEs and not only provided quantitative data that compared with conventional analytical approaches, but also provided new and complementary information via a nondestructive approach with high spatial resolution. It was shown that the Raman approach could be used to predict chronological age of the clinical samples (P<0.001) and a difference in the Raman spectra between genders was highly significant (P<0.000001). With further development, this Raman-based approach has the potential for noninvasive examination of AGE adducts in living eyes and ultimately to assess their precise pathogenic role in age-related diseases.
C1 Queens Univ Belfast, Fac Med & Hlth Sci, Sch Biomed Sci, Ctr Vis Sci, Belfast, Antrim, North Ireland.
   Queens Univ Belfast, Sch Chem & Chem Engn, Belfast, Antrim, North Ireland.
   Queens Univ Belfast, Ctr Clin Raman Microscopy, Belfast, Antrim, North Ireland.
   Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA.
   Univ Texas, Med Branch, Dept Ophthalmol & Vis Sci, Galveston, TX 77550 USA.
C3 Queens University Belfast; Queens University Belfast; Queens University
   Belfast; University of South Carolina; University of South Carolina
   System; University of South Carolina Columbia; University of Texas
   System; University of Texas Medical Branch Galveston
RP Stitt, AW (通讯作者)，Queens Univ Belfast, Royal Victoria Hosp, Ctr Vis Sci, Sch Biomed Sci, Belfast BT12 6BA, Antrim, North Ireland.
EM a.stitt@qub.ac.uk
RI Stitt, Alan/A-9842-2009; Beattie, James Renwick/I-4506-2015; Beattie,
   Renwick/B-7810-2008
OI Stitt, Alan/0000-0002-8647-9918; Beattie, James
   Renwick/0000-0002-0205-717X; 
FU MRC [G0600053] Funding Source: UKRI; NATIONAL INSTITUTE OF DIABETES AND
   DIGESTIVE AND KIDNEY DISEASES [R37DK019971, R01DK019971] Funding Source:
   NIH RePORTER; Medical Research Council [G0600053] Funding Source:
   Medline; NIDDK NIH HHS [DK19971] Funding Source: Medline; Wellcome Trust
   [WT066193] Funding Source: Medline
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NR 51
TC 95
Z9 96
U1 0
U2 33
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD NOV
PY 2007
VL 21
IS 13
BP 3542
EP 3552
DI 10.1096/fj.06-7896com
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA 225KW
UT WOS:000250517800017
PM 17567569
DA 2022-11-30
ER

PT J
AU Karotki, A
   Khurana, M
   Lepock, JR
   Wilson, BC
AF Karotki, A
   Khurana, M
   Lepock, JR
   Wilson, BC
TI Simultaneous two-photon excitation of photofrin in relation to
   photodynamic therapy
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID SINGLET OXYGEN GENERATION; CROSS-SECTIONS; IN-VITRO; ABSORPTION;
   FLUORESCENCE; LASER; ENHANCEMENT; PORPHYRINS; PHOTOSENSITIZERS;
   SELECTIVITY
AB Photodynamic therapy (PDT), the use of light-activated drugs (photosensitizers), is an emerging treatment modality for tumors as well as various nononcologic conditions. Single-photon (1-gamma) PDT is limited by low specificity of the photosensitizer, leading to damage to healthy tissue adjacent to the diseased target tissue. One solution is to use simultaneous two-photon (2-gamma) excitation with ultrafast pulses of near-IR light. Due to the nonlinear interaction mechanism, 2-gamma excitation with a focused beam is localized in three dimensions, allowing treatment volumes on the order of femtoliters. We propose that this will be valuable in PDT of age-related macular degeneration (AMD), which causes blindness due to abnormal choroidal neovasculature and which is currently treated by 1-gamma PDT. Here, Photofrin has been used as the photosensitizer to demonstrate proof-of-principle of 2-gamma killing of vascular endothelial cells in vitro. The 2-gamma absorption properties of Photofrin were investigated in the 750-900 nm excitation wavelength range. It was shown that 2-gamma excitation dominates over 1-gamma excitation above 800 rim. The 2-gamma absorption spectrum of Photofrin in the 800-900 nm excitation wavelength range was measured. The 2-gamma cross section decreased from about 10 GM (1 GM = 10-(50) cm(4) s/photon) at 800 nm to 5 GM at 900 nm. Adherent YPEN-1 endothelial cells were then incubated with Photofrin for 24 h and then treated by PDT at 850 nm where the 1-gamma contribution was negligible. Cell death was monitored with the use of 2-gamma scanning laser microscopy. The light doses required for killing were high (6300 J cm(-2) for similar to 50% killing), but 2-gamma cytotoxicity was unequivocally demonstrated. Although Photofrin is, per se, not a good choice for 2-gamma PDT due to its low 2-gamma cross section, this work provides baseline data to guide the development of novel photosensitizers with much higher 2-gamma cross sections (> 100 GM), which will be required for 2-gamma PDT of AMD (and other conditions) to be clinically practical.
C1 Univ Toronto, Ontario Canc Inst, Div Biophys & Bioimaging, Toronto, ON, Canada.
C3 University of Toronto; University Toronto Affiliates; University Health
   Network Toronto
RP Wilson, BC (通讯作者)，Univ Toronto, Ontario Canc Inst, Div Biophys & Bioimaging, 500 Sherbourne St, Toronto, ON, Canada.
EM wilson@uhnres.utoronto.ca
OI Wilson, Brian C./0000-0001-5543-666X
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NR 55
TC 150
Z9 154
U1 0
U2 52
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0031-8655
EI 1751-1097
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD MAR-APR
PY 2006
VL 82
IS 2
BP 443
EP 452
DI 10.1562/2005-08-24-RA-657
PG 10
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 036CK
UT WOS:000237048300016
PM 16613497
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Gong, Y
   Tomita, Y
   Edin, ML
   Ren, AL
   Ko, MJ
   Yang, J
   Bull, E
   Zeldin, DC
   Hellstrom, A
   Fu, ZJ
   Smith, LEH
AF Gong, Yan
   Tomita, Yohei
   Edin, Matthew L.
   Ren, Anli
   Ko, Minji
   Yang, Jay
   Bull, Edward
   Zeldin, Darryl C.
   Hellstrom, Ann
   Fu, Zhongjie
   Smith, Lois E. H.
TI Cytochrome P450 oxidase 2J inhibition suppresses choroidal
   neovascularization in mice
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE Cytochrome P450 oxidase 2J; Long -chain polyunsaturated fatty acid;
   Lipid metabolism; Choroidal neovascularization; Age -related macular
   degeneration; Tumor necrosis factor-?
ID MACULAR DEGENERATION; ENDOTHELIAL EXPRESSION; ACID; METABOLITES;
   PROGRESSION; PREVALENCE; OMEGA-3; INJURY
AB Introduction: Choroidal neovascularization (CNV) in age-related macular degeneration (AMD) leads to blindness. It has been widely reported that increased intake of co-3 long-chain polyunsaturated fatty acids (LCPUFA) diets reduce CNV. Of the three major pathways metabolizing co-3 (and co-6 LCPUFA), the cyclooxygenase and lip-oxygenase pathways generally produce pro-angiogenic metabolites from co-6 LCPUFA and anti-angiogenic ones from co-3 LCPUFA. Howevehr, cytochrome P450 oxidase (CPY) 2C produces pro-angiogenic metabolites from both co-6 and co-3 LCPUFA. The effects of CYP2J2 products on ocular neovascularization are still unknown. Understanding how each metabolic pathway affects the protective effect of co-3 LCPUFA on retinal neo-vascularization may lead to therapeutic interventions.Objectives: To investigate the effects of LCPUFA metabolites through CYP2J2 pathway and CYP2J2 regulation on CNV both in vivo and ex vivo. Methods: The impact of CYP2J2 overexpression and inhibition on neovascularization in the laser-induced CNV mouse model was assessed. The plasma levels of CYP2J2 metabolites were measured by liquid chromatography and tandem mass spectroscopy. The choroidal explant sprouting assay was used to investigate the effects of CYP2J2 inhibition and specific LCPUFA CYP2J2 metabolites on angiogenesis ex vivo.Results: CNV was exacerbated in Tie2-Cre CYP2J2-overexpressing mice and was associated with increased levels of plasma docosahexaenoic acids. Inhibiting CYP2J2 activity with flunarizine decreased CNV in both co-6 and co-3 LCPUFA-fed wild-type mice. In Tie2-Cre CYP2J2-overexpressing mice, flunarizine suppressed CNV by 33 % and 36 % in co-6, co-3 LCPUFA diets, respectively, and reduced plasma levels of CYP2J2 metabolites. The pro-angiogenic role of CYP2J2 was corroborated in the choroidal explant sprouting assay. Flunarizine attenuated ex vivo choroidal sprouting, and 19,20-EDP, a co-3 LCPUFA CYP2J2 metabolite, increased sprouting. The combined inhibition of CYP2J2 with flunarizine and CYP2C8 with montelukast further enhanced CNV suppression via tumor necrosis factor-alpha suppression.Conclusions: CYP2J2 inhibition augmented the inhibitory effect of co-3 LCPUFA on CNV. Flunarizine suppressed pathological choroidal angiogenesis, and co-treatment with montelukast inhibiting CYP2C8 further enhanced the effect. CYP2 inhibition might be a viable approach to suppress CNV in AMD.
C1 [Gong, Yan; Ren, Anli] Wuhan Univ, Zhongnan Hosp, Dept Biol Repositories, Wuhan, Peoples R China.
   [Gong, Yan; Tomita, Yohei; Ko, Minji; Yang, Jay; Bull, Edward; Fu, Zhongjie; Smith, Lois E. H.] Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA.
   [Edin, Matthew L.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Ren, Anli] Wuhan Univ, Zhongnan Hosp, Dept Ophthalmol, Wuhan, Peoples R China.
   [Hellstrom, Ann] Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden.
C3 Wuhan University; Harvard University; Boston Children's Hospital;
   Harvard Medical School; National Institutes of Health (NIH) - USA; NIH
   National Institute of Environmental Health Sciences (NIEHS); Wuhan
   University; University of Gothenburg
RP Smith, LEH (通讯作者)，Harvard Med Sch, Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.
EM lois.smith@childrens.harvard.edu
OI Tomita, Yohei/0000-0003-1013-5737; Yang, Jay/0000-0003-0790-7951
FU National Institutes of Health [R24EY024868, R01EY017017, R01EY030904,
   R01EY032492]; BCH IDDRC [1U54HD090255]; Massa-chusetts Lions Eye
   Research Fund; National Natural Science Foundation of China [81800429];
   Young and Middle-Aged Medical Backbone Talents of Wuhan [WHQG201902];
   Application Foundation Frontiers Project of Wuhan [2020020601012221];
   Medical Science and Technology Innovation Platform Construction Support
   Project of Zhongnan Hospital of Wuhan University [PTXM2022009]; Alcon
   Research Institute
FX This work was supported by the National Institutes of Health
   (R24EY024868, R01EY017017, and R01EY030904 to LEHS, R01EY032492 to ZF) ,
   BCH IDDRC (1U54HD090255) ; and the Massa-chusetts Lions Eye Research
   Fund to LEHS and ZF, National Natural Science Foundation of China
   (81800429 to YG) , Young and Middle-Aged Medical Backbone Talents of
   Wuhan (WHQG201902 to YG) , Application Foundation Frontiers Project of
   Wuhan (2020020601012221 to YG) and Medical Science and Technology
   Innovation Platform Construction Support Project of Zhongnan Hospital of
   Wuhan University (PTXM2022009 to YG) . The Alcon Research Institute, and
   Bert M. Glaser, MD Award to YT. The funders had no involvement in the
   study design, collection, analysis, interpretation of data, or report
   writing.
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TC 0
Z9 0
U1 3
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
EI 1532-8600
J9 METABOLISM
JI Metab.-Clin. Exp.
PD SEP
PY 2022
VL 134
AR 155266
DI 10.1016/j.metabol.2022.155266
PG 8
WC Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Endocrinology & Metabolism
GA 4P7EV
UT WOS:000855555700001
PM 35868524
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Nair, DSR
   Thomas, BB
AF Nair, Deepthi S. Rajendran
   Thomas, Biju B.
TI Stem Cell-based Treatment Strategies for Degenerative Diseases of the
   Retina
SO CURRENT STEM CELL RESEARCH & THERAPY
LA English
DT Review
DE Retinal degenerative disease; retinitis pigmentosa (RP); age-related
   macular degeneration (AMD); stem cell therapy; retinal progenitor cells;
   ESC-RPE; iPSC-RPE
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; PROGENITOR CELLS;
   PHOTORECEPTOR PRECURSORS; NANOFIBROUS SCAFFOLDS; RODENT MODEL; IN-VITRO;
   TRANSPLANTATION; RPE; TISSUE
AB Background: The main cause of progressive vision impairment in retinal degenerative diseases is the dysfunction of photoreceptors and the underlying retinal pigment epithelial cells. The inadequate regenerative capacity of the neural retina and lack of established therapeutic options demand the development of clinical-grade protocols to halt the degenerative process in the eye or replace the damaged cells by using stem cell-derived products. Recently, stem cell-based regenerative therapies have been at the forefront of clinical investigations for retinal dystrophies. Objective: This article will review different stem cell-based therapies currently employed for retinal degenerative diseases, recent clinical trials, and major challenges in the translation of these therapies from bench to bedside. Methodology: A systematic literature review was conducted to identify potentially relevant articles published in MEDLINE/PubMed, Embase, ClinicalTrials.gov, Drugs@FDA, European Medicines Agency, and World Health Organization International Clinical Trials Registry Platform. Results: Transplantation of healthy cells to replace damaged cells in the outer retina is a clinically relevant concept because the inner retina that communicates with the visual areas of the brain remains functional even after the photoreceptors are completely lost. Various methods have been established for the differentiation of pluripotent stem cells into different retinal cell types that can be used for therapies. Factors released from transplanted somatic stem cells showed trophic support and photoreceptor rescue during the early stages of the disease. Several preclinical and phase I/II clinical studies using terminally differentiated photoreceptor/retinal pigment epithelial cells derived from pluripotent stem cells have shown proof of concept for visual restoration in Age-related Macular Degeneration (AMD), Stargardt disease, and Retinitis Pigmentosa (RP). Conclusion: Cell replacement therapy has great potential for vision restoration. The results obtained from the initial clinical trials are encouraging and indicate its therapeutic benefits. The current status of the therapies suggests that there is a long way to go before these results can be applied to routine clinical practice. Input from the ongoing multicentre clinical trials will give a more refined idea for the future design of clinical-grade protocols to transplant GMP level HLA matched cells.
C1 [Nair, Deepthi S. Rajendran; Thomas, Biju B.] Univ Southern Calif, Roski Eye Inst, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90007 USA.
   [Thomas, Biju B.] Univ Southern Calif, USC Ginsburg Inst Biomed Therapeut, Los Angeles, CA 90007 USA.
C3 University of Southern California; University of Southern California
RP Thomas, BB (通讯作者)，Univ Southern Calif, Roski Eye Inst, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90007 USA.
EM biju.thomas@med.usc.edu
RI Rajendran Nair, Deepthi S./AAE-2769-2022
OI Rajendran Nair, Deepthi S./0000-0001-8851-5241
FU CIRM (California Institute for Regenerative Medicine) [DISC1-09912,
   DR3-07438]; Research to Prevent Blindness, New York, NY; Bright Focus
   Foundation [M2016186]; National Eye Institute of the National Institutes
   of Health [P30EY029220]
FX This study was supported by the CIRM (California Institute for
   Regenerative Medicine) grants (DISC1-09912 PIThomas,
   DR3-07438-PI-Humayun), Unrestricted Grant to the Department of
   Ophthalmology from Research to Prevent Blindness, New York, NY, and
   support from Bright Focus Foundation (M2016186, Thomas, PI). Research
   reported in this publication was supported by the National Eye Institute
   of the National Institutes of Health under Award Number P30EY029220.
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NR 97
TC 2
Z9 2
U1 1
U2 2
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1574-888X
EI 2212-3946
J9 CURR STEM CELL RES T
JI Curr. Stem Cell Res. Ther.
PY 2022
VL 17
IS 3
BP 214
EP 225
DI 10.2174/1574888X16666210804112104
PG 12
WC Cell & Tissue Engineering; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 1Z0TE
UT WOS:000808545800004
PM 34348629
DA 2022-11-30
ER

PT J
AU Clarkson-Townsend, DA
   Douglass, AJ
   Singh, A
   Allen, RS
   Uwaifo, IN
   Pardue, MT
AF Clarkson-Townsend, Danielle A.
   Douglass, Amber J.
   Singh, Anayesha
   Allen, Rachael S.
   Uwaifo, Ivie N.
   Pardue, Machelle T.
TI Impacts of high fat diet on ocular outcomes in rodent models of visual
   disease
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE High fat diet; HFD; Diet-induced obesity; Vision; Retina; Age-related
   macular degeneration; Diabetic retinopathy; Diabetes
ID RETINAL-PIGMENT EPITHELIUM; BASAL LAMINAR DEPOSIT; SUB-RPE DEPOSITS;
   MACULAR DEGENERATION; INDUCED OBESITY; PERIPHERAL NEUROPATHY;
   DIABETIC-RETINOPATHY; BRUCHS MEMBRANE; ANIMAL-MODELS; INSULIN-RESISTANCE
AB High fat diets (HFD) have been utilized in rodent models of visual disease for over 50 years to model the effects of lipids, metabolic dysfunction, and diet-induced obesity on vision and ocular health. HFD treatment can recapitulate the pathologies of some of the leading causes of blindness, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) in rodent models of visual disease. However, there are many important factors to consider when using and interpreting these models. To synthesize our current understanding of the importance of lipid signaling, metabolism, and inflammation in HFD-driven visual disease processes, we systematically review the use of HFD in mouse and rat models of visual disease. The resulting literature is grouped into three clusters: models that solely focus on HFD treatment, models of diabetes that utilize both HFD and streptozotocin (STZ), and models of AMD that utilize both HFD and genetic models and/or other exposures. Our findings show that HFD profoundly affects vision, retinal function, many different ocular tissues, and multiple cell types through a variety of mechanisms. We delineate how HFD affects the cornea, lens, uvea, vitreous humor, retina, retinal pigmented epithelium (RPE), and Bruch?s membrane (BM). Furthermore, we highlight how HFD impairs several retinal cell types, including glia (microglia), retinal ganglion cells, bipolar cells, photoreceptors, and vascular support cells (endothelial cells and pericytes). However, there are a number of gaps, limitations, and biases in the current literature. We highlight these gaps and discuss experimental design to help guide future studies. Very little is known about how HFD impacts the lens, ciliary bodies, and specific neuronal populations, such as rods, cones, bipolar cells, amacrine cells, and retinal ganglion cells. Additionally, sex bias is an important limitation in the current literature, with few HFD studies utilizing female rodents. Future studies should use ingredient-matched control diets (IMCD), include both sexes in experiments to evaluate sex-specific outcomes, conduct longitudinal metabolic and visual measurements, and capture acute outcomes. In conclusion, HFD is a systemic exposure with profound systemic effects, and rodent models are invaluable in understanding the impacts on visual and ocular disease.
C1 [Clarkson-Townsend, Danielle A.] Emory Univ, Gangarosa Dept Environm Hlth, Atlanta, GA 30322 USA.
   [Clarkson-Townsend, Danielle A.; Douglass, Amber J.; Singh, Anayesha; Allen, Rachael S.; Uwaifo, Ivie N.; Pardue, Machelle T.] Atlanta VA Healthcare Syst, Ctr Visual & Neurocognit Rehabil, Decatur, GA USA.
   [Singh, Anayesha] Emory Univ, Emory Ctr Eth, Atlanta, GA 30322 USA.
   [Allen, Rachael S.; Pardue, Machelle T.] Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA.
   [Allen, Rachael S.; Pardue, Machelle T.] Emory Univ, Atlanta, GA 30322 USA.
   [Uwaifo, Ivie N.] Emory Univ, Dept Neurosci, Atlanta, GA 30322 USA.
C3 Emory University; Emory University; University System of Georgia;
   Georgia Institute of Technology; Emory University; Emory University
RP Pardue, MT (通讯作者)，313 Ferst Dr,Room 4104, Atlanta, GA 30332 USA.
EM machelle.pardue@bme.gatech.edu
RI Pardue, Machelle T/N-9795-2013
OI (Clarkson-Townsend) Wallace, Danielle/0000-0001-7033-2172
FU National Institutes of Health [NIH-NICHD F31 HD097918, NIH-NIEHS T32
   ES012870]; National Institutes of Health (NIH-NEI Core Grant)
   [P30EY006360]; Department of Veterans Affairs (Rehabilitation Research
   and Development Senior Research Career Scientist Award) [RX003134];
   Department of Veterans Affairs (Career Development Award) [CDA-2
   RX002928]
FX This work was supported by funding from the National Institutes of
   Health (NIH-NICHD F31 HD097918 [to DACT], NIH-NIEHS T32 ES012870 [to
   DACT], NIH-NEI Core Grant P30EY006360) and the Department of Veterans
   Affairs (Rehabilitation Research and Development Senior Research Career
   Scientist Award RX003134 [to MTP] and Career Development Award CDA-2
   RX002928 [to RSA]). The study sponsors did not have any role in the
   study design, collection, analysis, interpretation of the data, writing
   of the report, or the decision to submit the paper for publication.
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NR 196
TC 9
Z9 10
U1 1
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAR
PY 2021
VL 204
AR 108440
DI 10.1016/j.exer.2021.108440
EA JAN 2021
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RC8GZ
UT WOS:000633033700006
PM 33444582
OA hybrid, Green Accepted
DA 2022-11-30
ER

EF