﻿FN Clarivate Analytics Web of Science
VR 1.0
PT J
AU Mullins, RF
   Schoo, DP
   Sohn, EH
   Flamme-Wiese, MJ
   Workamelahu, G
   Johnston, RM
   Wang, K
   Tucker, BA
   Stonet, EM
AF Mullins, Robert F.
   Schoo, Desi P.
   Sohn, Elliott H.
   Flamme-Wiese, Miles J.
   Workamelahu, Grefachew
   Johnston, Rebecca M.
   Wang, Kai
   Tucker, Budd A.
   Stonet, Edwin M.
TI The Membrane Attack Complex in Aging Human Choriocapillaris Relationship
   to Macular Degeneration and Choroidal Thinning
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; AGE-RELATED MACULOPATHY; FACTOR-H
   POLYMORPHISM; BRUCHS MEMBRANE; ALTERNATIVE PATHWAY; BLOOD-FLOW; HUMAN
   EYES; DRUSEN; ACTIVATION; AMD
AB Age-related macular degeneration (AMD) is a common disease that can result in severe visual impairment. Abnormal regulation of the complement system has been implicated in its pathogenesis, and CFH polymorphisms contribute substantially to risk. How these polymorphisms exert their effects is poorly understood. We performed enzyme-linked immunosorbent assay (ELISA) analysis on young, aged, and AMD choroids to determine the abundance of the membrane attack complex (MAC) and performed immunofluorescence studies on eyes from 117 donors to evaluate the MAC in aging, early AMD, and advanced AMD. Morphometric studies were performed on eyes with high- or low-risk CFH genotypes. ELISA confirmed that MAC increases significantly with aging and with AMD. MAC was localized to Bruch's membrane and the choriocapillaris and was detectable at low levels as early as 5 years of age. Hard drusen were labeled with anti-MAC antibody, but large or confluent drusen and basal deposits were generally unlabeled. Labeling of retinal pigment epithelium was observed in some cases of advanced AMD, but not in early disease. Eyes homozygous for the high-risk CFH genotype had thinner choroids than low-risk homozygotes (P < 0.05). These findings suggest that increased complement activation in AMD and in high-risk genotypes can lead to loss of endothelial cells in early AMD. Treatments to protect the choriocapillaris in early AMD are needed.
C1 [Mullins, Robert F.; Schoo, Desi P.; Sohn, Elliott H.; Flamme-Wiese, Miles J.; Workamelahu, Grefachew; Johnston, Rebecca M.; Tucker, Budd A.; Stonet, Edwin M.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
   [Mullins, Robert F.; Schoo, Desi P.; Sohn, Elliott H.; Flamme-Wiese, Miles J.; Workamelahu, Grefachew; Johnston, Rebecca M.; Wang, Kai; Tucker, Budd A.; Stonet, Edwin M.] Univ Iowa, Dept Biostat, Iowa City, IA USA.
   [Wang, Kai] Univ Iowa, Stephen A Wynn Inst Vis Res, Iowa City, IA 52242 USA.
C3 University of Iowa; University of Iowa; University of Iowa
RP Mullins, RF (通讯作者)，Stephen A Wynn Inst Vis Res, Dept Ophthalmol & Visual Sci, 4135EM MERF,375 Newton Rd, Iowa City, IA 52242 USA.
EM robert-rnullins@uiowa.edu
RI Mullins, Robert F/I-6717-2013
OI Mullins, Robert/0000-0002-5006-0891; Stone, Edwin
   M./0000-0003-3343-4414; Sohn, Elliott/0000-0002-3778-9362; Tucker,
   Budd/0000-0003-2178-1742
FU NIH [R01EY017451, R01EY016822, DP2-OD007483-01]; Howard Hughes Medical
   Institute; Elmer and Sylvia Sramek Charitable Foundation; Doris Duke
   Clinical Research Fellowship Program; Research to Prevent Blindness;
   Stephen A. Wynn Foundation; NATIONAL EYE INSTITUTE [R01EY016822,
   R01EY017451] Funding Source: NIH RePORTER; OFFICE OF THE DIRECTOR,
   NATIONAL INSTITUTES OF HEALTH [DP2OD007483] Funding Source: NIH RePORTER
FX Supported in part by NIH grants R01EY017451 (R.F.M.), R01EY016822
   (E.M.S.), and DP2-OD007483-01 (B.A.T.); the Howard Hughes Medical
   Institute (EMS.); The Elmer and Sylvia Sramek Charitable Foundation
   (R.F.M. and B.A.T.); the Doris Duke Clinical Research Fellowship Program
   (D.S.); an unrestricted grant to the Department of Ophthalmology and
   Visual Sciences from Research to Prevent Blindness; the Hansjoerg E. J.
   W. Kolder, M.D., Ph.D., Professorship in Best Disease Research (R.F.M.);
   and the Stephen A. Wynn Foundation.
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NR 67
TC 131
Z9 135
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD NOV
PY 2014
VL 184
IS 11
BP 3142
EP 3153
DI 10.1016/j.ajpath.2014.07.017
PG 12
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA AS0LS
UT WOS:000343969200025
PM 25204844
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Yang, SJ
   Jo, H
   Kim, JG
   Jung, SH
AF Yang, Sung Jae
   Jo, Hyoung
   Kim, June-Gone
   Jung, Sang Hoon
TI Baicalin Attenuates Laser-Induced Choroidal Neovascularization
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; baicalin; choroidal
   neovascularization; fluorescein angiography; VEGF
ID INTRAVITREAL TRIAMCINOLONE ACETONIDE; ENDOTHELIAL GROWTH-FACTOR; MACULAR
   DEGENERATION; RETINAL CELLS; AQUEOUS FLARE; ANGIOGENESIS; MECHANISMS;
   EXPRESSION; COMPONENTS; RANIBIZUMAB
AB Purpose: To determine whether intravitreally-injected baicalin inhibits the growth of choroidal neovascularization (CNV) experimentally induced via laser photocoagulation through analysis of angiogenic factors.
   Materials and methods: Six CNVs were induced in the left eyes of 8-week-old male Brown Norway rats. Immediately after the induction of CNV, 4 mu l of baicalin solution (0.1, 1 or 5 nmol) and 4 mu l of a solution containing 100 mu g of bevacizumab were slowly injected into the vitreous cavity under direct observation with an operating microscope. At 14 days after CNV induction, fluorescein angiography (FA) was performed, and choroidal flat mounts were produced for quantitative assessment of CNV. The levels of the anti-angiogenic proteins vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and matrix metalloproteinase-2 (MMP-2) were determined via Western blot analysis.
   Results: FA of bevacizumab- and baicalin-treated rats showed significantly reduced CNV and leakage from the CNV lesions compared to control rats at day 14. Choroidal flat mounts revealed that baicalin inhibited the growth of CNV lesions in a dose-dependent manner. Western blot analysis demonstrated that baicalin significantly attenuated the up-regulation of VEGF, PDGF and MMP-2.
   Conclusion: Baicalin suppressed laser-induced CNV formation in rats. These results suggest that baicalin should be considered as a candidate drug for treating exudative age-related macular degeneration.
C1 [Yang, Sung Jae] Univ Ulsan, Dept Ophthalmol, Gangneung Asan Hosp, Kangnung, Gangwon, South Korea.
   [Jo, Hyoung; Jung, Sang Hoon] KIST, Funct Food Ctr, Kangnung, Gangwon, South Korea.
   [Kim, June-Gone] Univ Ulsan, Asan Med Ctr, Dept Ophthalmol, Seoul, South Korea.
C3 University of Ulsan; Korea Institute of Science & Technology (KIST);
   University of Ulsan; Asan Medical Center
RP Jung, SH (通讯作者)，KIST, Gangneung Inst, Funct Food Ctr, Daejeon Dong 210340, Gangneung, South Korea.
EM june-kim@amc.seoul.kr; shjung507@gmail.com
FU Asan Institute of Life Science Grant [2008-160]; Korea Institute of
   Science and Technology (KIST), Republic of Korea [2Z03850]
FX The authors declare no financial conflict of interest. This work was
   financially supported by the Asan Institute of Life Science Grant (Grant
   2008-160), and by an intramural grant (2Z03850) from the Korea Institute
   of Science and Technology (KIST), Republic of Korea.
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NR 44
TC 9
Z9 12
U1 1
U2 9
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 JUL
PY 2014
VL 39
IS 7
BP 745
EP 751
DI 10.3109/02713683.2013.868908
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AI6OS
UT WOS:000336995500013
PM 24502359
DA 2022-11-30
ER

PT J
AU Yang, SD
   Chen, YF
   Ahmadie, R
   Ho, EA
AF Yang, Sidi
   Chen, Yufei
   Ahmadie, Roien
   Ho, Emmanuel A.
TI Advancements in the field of intravaginal siRNA delivery
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Review
DE Intravaginal drug delivery; RNA interference (RNAi); Liposomes;
   Nanoparticles; HIV/AIDS; Microbicides
ID SMALL INTERFERING RNA; HUMAN-IMMUNODEFICIENCY-VIRUS; CELL-PENETRATING
   PEPTIDES; DOUBLE-STRANDED-RNA; HYDROPHILIC POLYMERIC CHAINS; VAGINAL GEL
   FORMULATIONS; HERPES-SIMPLEX VIRUS-2; IN-VIVO GROWTH; DRUG-DELIVERY;
   TRANSFECTION EFFICIENCY
AB The vaginal tract is a suitable site for the administration of both local and systemic acting drugs. There are numerous vaginal products on the market such as those approved for contraception, treatment of yeast infection, hormonal replacement therapy, and feminine hygiene. Despite the potential in drug delivery, the vagina is a complex and dynamic organ that requires greater understanding. The recent discovery that injections of double stranded RNA (dsRNA) in Caenorhabditis elegans (C. elegans) results in potent gene specific silencing, was a major scientific revolution. This phenomenon known as RNA interference (RNAi), is believed to protect host genome against invasion by mobile genetic elements such as transposons and viruses. Gene silencing or RNAi has opened new potential opportunities to study the function of a gene in an organism. Furthermore, its therapeutic potential is being investigated in the field of sexually transmitted infections such as human immunodeficiency virus (HIV) and other diseases such as age-related macular degeneration (AMD), diabetes, hypercholesterolemia, respiratory disease, and cancer. This review will focus on the therapeutic potential of siRNA for the treatment and/or prevention of infectious diseases such as HIV, HPV, and HSV within the vaginal tract. Specifically, formulation design parameters to improve siRNA stability and therapeutic efficacy in the vaginal tract will be discussed along with challenges, advancements, and future directions of the field. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Yang, Sidi; Chen, Yufei; Ahmadie, Roien; Ho, Emmanuel A.] Univ Manitoba, Fac Pharm, Winnipeg, MB R3E 0T5, Canada.
C3 University of Manitoba
RP Ho, EA (通讯作者)，Univ Manitoba, Fac Pharm, Apotex Ctr, 750 McDermot Ave,Room 329, Winnipeg, MB R3E 0T5, Canada.
EM emmanuel_ho@umanitoba.ca
RI Chen, Yufei/R-7259-2016
OI Chen, Yufei/0000-0002-5782-3556; Ho, Emmanuel/0000-0003-4729-9970
FU Bill and Melinda Gates Foundation [OPP1007233GCE]; Canadian Institutes
   of Health Research [MOP110981]; Manitoba Medical Service Foundation
   [MMSF811.05]; Faculty of Graduate Studies International Graduate Student
   Entrance Scholarship; Manitoba Health Research Council
FX This work was supported in part by grants awarded to Dr. Emmanuel A. Ho
   from the Bill and Melinda Gates Foundation Grand Challenges Explorations
   Grant (OPP1007233GCE), the Canadian Institutes of Health Research
   (MOP110981), and the Manitoba Medical Service Foundation (MMSF811.05).
   Sidi Yang is grateful for the financial support received from the
   Faculty of Graduate Studies International Graduate Student Entrance
   Scholarship, and Yufei Chen is grateful for the financial support
   received from the Manitoba Health Research Council Graduate Studentship.
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NR 171
TC 43
Z9 46
U1 0
U2 75
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD APR 10
PY 2013
VL 167
IS 1
BP 29
EP 39
DI 10.1016/j.jconrel.2012.12.023
PG 11
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Pharmacology & Pharmacy
GA 113OT
UT WOS:000316678100004
PM 23298612
DA 2022-11-30
ER

PT J
AU Abdel-Aal, EM
   Akhtar, H
   Zaheer, K
   Ali, R
AF Abdel-Aal, El-Sayed M.
   Akhtar, Humayoun
   Zaheer, Khalid
   Ali, Rashida
TI Dietary Sources of Lutein and Zeaxanthin Carotenoids and Their Role in
   Eye Health
SO NUTRIENTS
LA English
DT Review
DE lutein and zeaxanthin carotenoids; dietary sources; eye health;
   high-lutein foods; bioavailability
ID AGE-RELATED MACULOPATHY; PIGMENT OPTICAL-DENSITY; MACULAR PIGMENT;
   TISSUE CONCENTRATIONS; SERUM CONCENTRATIONS; ANTIOXIDANT ACTIVITY;
   VISUAL IMPAIRMENT; NUCLEAR CATARACT; BINDING PROTEIN; PROTECTIVE ROLE
AB The eye is a major sensory organ that requires special care for a healthy and productive lifestyle. Numerous studies have identified lutein and zeaxanthin to be essential components for eye health. Lutein and zeaxanthin are carotenoid pigments that impart yellow or orange color to various common foods such as cantaloupe, pasta, corn, carrots, orange/yellow peppers, fish, salmon and eggs. Their role in human health, in particular the health of the eye, is well established from epidemiological, clinical and interventional studies. They constitute the main pigments found in the yellow spot of the human retina which protect the macula from damage by blue light, improve visual acuity and scavenge harmful reactive oxygen species. They have also been linked with reduced risk of age-related macular degeneration (AMD) and cataracts. Research over the past decade has focused on the development of carotenoid-rich foods to boost their intake especially in the elderly population. The aim of this article is to review recent scientific evidences supporting the benefits of lutein and zexanthin in preventing the onset of two major age-related eye diseases with diets rich in these carotenoids. The review also lists major dietary sources of lutein and zeaxanthin and refers to newly developed foods, daily intake, bioavailability and physiological effects in relation to eye health. Examples of the newly developed high-lutein functional foods are also underlined.
C1 [Abdel-Aal, El-Sayed M.; Akhtar, Humayoun] Agr & Agri Food Canada, Guelph Food Res Ctr, Guelph, ON N1G 5C9, Canada.
   [Ali, Rashida] Univ Karachi, ICCBS, Dept Food Sci & Technol, Karachi 75270, Pakistan.
   [Ali, Rashida] English Biscuit Mfg Pvt Ltd, Korangi Ind Area, Karachi 74900, Pakistan.
C3 Agriculture & Agri Food Canada; University of Karachi
RP Abdel-Aal, EM (通讯作者)，Agr & Agri Food Canada, Guelph Food Res Ctr, Guelph, ON N1G 5C9, Canada.
EM elsayed.abdelaal@agr.gc.ca; humayoun.akhtar@agr.gc.ca;
   kzaheer2000@gmail.com; rashida338@gmail.com
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NR 99
TC 251
Z9 266
U1 25
U2 270
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 2072-6643
J9 NUTRIENTS
JI Nutrients
PD APR
PY 2013
VL 5
IS 4
BP 1169
EP 1185
DI 10.3390/nu5041169
PG 17
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 131TP
UT WOS:000318019300009
PM 23571649
OA gold, Green Published, Green Submitted
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Hanganu, D
   Olah, N
   Vlase, L
   Marculescu, A
   Pintea, A
AF Hanganu, Daniela
   Olah, Neli
   Vlase, Laurian
   Marculescu, Angela
   Pintea, Adela
TI CHEMICAL RESEARCH OF CAROTENOIDS FROM CHENOPODIUM BONUS HENRICUS L.
   (CHENOPODIACEAE)
SO FARMACIA
LA English
DT Article
DE Chenopodium; carotenoids; HPLC-PDA; retinol equivalent; lutein
AB Chenopodium bonus henricus L. belongs to the Chenopodiaceae family and grows spontaneously in Romania. It is used for its wound healing, anti-arthritis and anticough properties. The plant also has nutritional value due to its high protein and iron content.
   The studies of the carotenoids in Chenopodium bonus henricus L., performed by spectral and chromatographic (high pressure liquid chromatography - photodiode array: HPLC-PDA) methods, are mentioned for the first time in this study. The analysis were performed on both saponified and non-saponified extracts. The aerial part of the plant (herba) contains 344.1mg total carotenoids/100g dry weight (51.3mg total carotenoids/100g fresh weight). Five xanthophylls were identified and quantified: neoxanthin, violaxanthin, lutein, zeaxanthin, beta-cryptoxantin, and two carotenes: alpha-carotene and beta-carotene. In the non-saponified extract lutein was the major carotenoid (176.54mg/100g dry weight), followed by beta-carotene (87.31mg/100g dry weight), then by violaxanthin and neoxanthin. The value of retinol equivalents (RE) calculated was 15320 by taking into account the alpha-carotene, beta-carotene and beta-criptoxanthin content. The results demonstrate that Chenopodium bonus henricus L. represents a rich source of provitamin A carotenoids and lutein, with high nutritional value. Raw plant or standardized extracts of Chenopodium bonus henricus L. can be used as dietary supplements for improving the vitamin A status and for prevention of Age-related Macular Degeneration.
C1 [Hanganu, Daniela] Univ Med & Pharm Iuliu Hatieganu, Fac Pharm, Dept Pharmacognosy Phytoterapy, Cluj Napoca, Romania.
   [Olah, Neli] Vasile Goldis Western Univ Arad, Arad & SC PlantExtrakt SRL, Dept Pharmaceut Ind, Radaia 407059, Cluj, Romania.
   [Vlase, Laurian] Univ Med & Pharm Iuliu Hatieganu, Fac Pharm, Dept Pharmaceut Technol & Biopharmaceut, Cluj Napoca, Romania.
   [Marculescu, Angela] Transilvania Univ, Dept Alimentary Chem, Brasov, Romania.
   [Pintea, Adela] Univ Agr Sci & Vet Med, Cluj Napoca, Romania.
C3 Iuliu Hatieganu University of Medicine & Pharmacy; Vasile Goldis Western
   University of Arad; Iuliu Hatieganu University of Medicine & Pharmacy;
   Transylvania University of Brasov; University of Agricultural Sciences &
   Veterinary Medicine Cluj Napoca
RP Vlase, L (通讯作者)，Univ Med & Pharm Iuliu Hatieganu, Fac Pharm, Dept Pharmaceut Technol & Biopharmaceut, 12 Ion Creanga St, Cluj Napoca, Romania.
EM vlaselaur@yahoo.com
RI Pintea, Adela/C-4521-2011; Vlase, Laurian/B-6311-2011; Vlase,
   Laurian/F-5294-2014
OI Pintea, Adela/0000-0002-9914-2070; Vlase, Laurian/0000-0002-0664-3387; 
FU CNCSIS-UEFISCSU [PNII - IDEI ID_854, 414/2007]
FX This work was supported by CNCSIS-UEFISCSU, project number PNII - IDEI
   ID_854, code 414/2007).
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NR 18
TC 3
Z9 3
U1 0
U2 9
PU SOC STIINTE FARMACEUTICE ROMANIA
PI BUCURESTI
PA BUCURESTI, STR TRAIAN VUIA 6, SECT 1, BUCURESTI, 020956, ROMANIA
SN 0014-8237
EI 2065-0019
J9 FARMACIA
JI Farmacia
PD NOV-DEC
PY 2012
VL 60
IS 6
BP 840
EP 849
PG 10
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 103PL
UT WOS:000315931200007
DA 2022-11-30
ER

PT J
AU Galor, A
   Lee, DJ
AF Galor, Anat
   Lee, David J.
TI Effects of smoking on ocular health
SO CURRENT OPINION IN OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; ocular health; ocular inflammation;
   smoking; thyroid-associated orbitopathy
ID THYROID-ASSOCIATED OPHTHALMOPATHY; FACTOR-H POLYMORPHISM;
   CIGARETTE-SMOKING; MACULAR DEGENERATION; RISK-FACTORS; DRY EYE;
   LOC387715/HTRA1 POLYMORPHISMS; PREVALENCE; GENE; ASSOCIATION
AB Purpose of review
   To review recent data on the effects of smoking on ocular health.
   Recent findings
   Smoking has been associated with a myriad of negative ocular health effects including age-related macular degeneration (ARMD) and cataract. Most recently, several papers have demonstrated a connection between smoking and ocular inflammation. Smokers are both more likely to develop ocular inflammation and to have more severe disease as manifested by poorer presenting vision and a higher risk of recurrent disease compared to nonsmokers. Smoking has also been shown to enhance the effect of genetic susceptibility with regards to the presence and development of ARMD. Finally, the negative effects of smoking on ocular disease have been increasingly documented in nonwhite populations outside of the USA. However, despite the abundance of data, public awareness on the adverse consequences of smoking on vision is lacking in the USA. In contrast, Australia improved public knowledge by launching a successful antitobacco health campaign highlighting the effects of smoking on ocular health.
   Summary
   These findings suggest that eye care professionals should discuss and offer options for smoking cessation as part of the management of patients with ocular diseases, especially in those with ocular inflammation, ARMD, lens opacities/cataract, and thyroid-associated orbitopathy. Health campaigns using existing medical data can improve public awareness on the connection between tobacco and visual impairment.
C1 [Galor, Anat] Univ Miami, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Lee, David J.] Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
   [Galor, Anat] Univ Miami, Sch Med, Miami Vet Adm Med Ctr, Miami, FL 33136 USA.
C3 Bascom Palmer Eye Institute; University of Miami; University of Miami;
   University of Miami
RP Galor, A (通讯作者)，Univ Miami, Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
EM agalor@med.miami.edu
FU Veterans Affairs; research to prevent blindness
FX This study was supported by a Veterans Affairs career development grant
   (Dr Galor), unrestricted grant from research to prevent blindness.
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NR 52
TC 52
Z9 52
U1 0
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8738
EI 1531-7021
J9 CURR OPIN OPHTHALMOL
JI Curr. Opin. Ophthalmol.
PD NOV
PY 2011
VL 22
IS 6
BP 477
EP 482
DI 10.1097/ICU.0b013e32834bbe7a
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 841UU
UT WOS:000296541200007
PM 21897240
DA 2022-11-30
ER

PT J
AU Gutierrez, DB
   Blakeley, L
   Goletz, PW
   Schey, KL
   Hanneken, A
   Koutalos, Y
   Crouch, RK
   Ablonczy, Z
AF Gutierrez, Danielle B.
   Blakeley, Lorie
   Goletz, Patrice W.
   Schey, Kevin L.
   Hanneken, Anne
   Koutalos, Yiannis
   Crouch, Rosalie K.
   Ablonczy, Zsolt
TI Mass spectrometry provides accurate and sensitive quantitation of A2E
SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; LIGHT-INDUCED DAMAGE; LIPOFUSCIN
   FLUOROPHORE; MACULAR DEGENERATION; RPE LIPOFUSCIN; CELLS;
   PHOTOREACTIVITY; BIOSYNTHESIS; INVOLVEMENT; PRECURSOR
AB Orange autofluorescence from lipofuscin in the lysosomes of the retinal pigment epithelium (RPE) is a hallmark of aging in the eye. One of the major components of lipofuscin is A2E, the levels of which increase with age and in pathologic conditions, such as Stargardt disease or age-related macular degeneration. In vitro studies have suggested that A2E is highly phototoxic and, more specifically, that A2E and its oxidized derivatives contribute to RPE damage and subsequent photoreceptor cell death. To date, absorption spectroscopy has been the primary method to identify and quantitate A2E. Here, a new mass spectrometric method was developed for the specific detection of low levels of A2E and compared to a traditional method of analysis. The new mass spectrometric method allows the detection and quantitation of approximately 10 000-fold less A2E than absorption spectroscopy and the detection and quantitation of low levels of oxidized A2E, with localization of the oxidation sites. This study suggests that identification and quantitation of A2E from tissue extracts by chromatographic absorption spectroscopy overestimates the amount of A2E. This mass spectrometric approach makes it possible to detect low levels of A2E and its oxidized metabolites with greater accuracy than traditional methods, thereby facilitating a more exact analysis of bis-retinoids in animal models of inherited retinal degeneration as well as in normal and diseased human eyes.
C1 [Gutierrez, Danielle B.; Blakeley, Lorie; Goletz, Patrice W.; Koutalos, Yiannis; Crouch, Rosalie K.; Ablonczy, Zsolt] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Schey, Kevin L.] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA.
   [Hanneken, Anne] Scripps Res Inst, Dept Mol & Expt, La Jolla, CA USA.
C3 Medical University of South Carolina; Vanderbilt University; Scripps
   Research Institute
RP Gutierrez, DB (通讯作者)，Med Univ S Carolina, Dept Ophthalmol, 171 Ashley Ave, Charleston, SC 29425 USA.
OI Hanneken, Anne/0000-0002-7390-2596
FU NIH [EY004939, EY020661, EY014850, C06 RR015455]; Research to Prevent
   Blindness (RPB; New York); NATIONAL CENTER FOR RESEARCH RESOURCES
   [C06RR015455] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R01EY014850, R01EY019065, R01EY004939, R21EY020661] Funding Source: NIH
   RePORTER
FX This study was supported by grants from NIH EY004939 (RKC), EY020661
   (ZA/RKC); EY014850 (YK) and an unrestricted award to the Department of
   Ophthalmology at MUSC from Research to Prevent Blindness (RPB; New
   York); RKC is a RPB Senior Scientific Investigator. Additionally, we
   would like to thank Jennifer Bethard for technical assistance. The mass
   spectrometry work was performed in the MUSC Mass Spectrometry Shared
   Resource Facility. Experimental animals were housed in a facility
   constructed with support from the National Institutes of Health, Grant
   Number C06 RR015455 from the Extramural Research Facilities Program of
   the National Center for Research Resources.
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NR 31
TC 19
Z9 19
U1 0
U2 2
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
   ENGLAND
SN 1474-905X
J9 PHOTOCH PHOTOBIO SCI
JI Photochem. Photobiol. Sci.
PY 2010
VL 9
IS 11
BP 1513
EP 1519
DI 10.1039/c0pp00230e
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics; Chemistry
GA 672QX
UT WOS:000283603100013
PM 20931136
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Bhisitkul, RB
   Winn, BJ
   Lee, OT
   Wong, J
   Pereira, DD
   Porco, TC
   He, XN
   Hahn, P
   Dunaief, JL
AF Bhisitkul, Robert B.
   Winn, Bryan J.
   Lee, On-Tat
   Wong, Joshua
   Pereira, Daniel de Souza
   Porco, Travis C.
   He, Xining
   Hahn, Paul
   Dunaief, Joshua L.
TI Neuroprotective effect of intravitreal triamcinolone acetonide against
   photoreceptor apoptosis in a rabbit model of subretinal hemorrhage
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID TISSUE-PLASMINOGEN ACTIVATOR; VERTEPORFIN PHOTODYNAMIC THERAPY; RETINAL
   PHOTIC INJURY; SPINAL-CORD INJURY; MACULAR DEGENERATION; SUBMACULAR
   HEMORRHAGE; CHOROIDAL NEOVASCULARIZATION; PNEUMATIC DISPLACEMENT;
   BACTERIAL-MENINGITIS; CONTROLLED TRIAL
AB PURPOSE. To study photoreceptor apoptosis and iron migration as mechanisms of retinotoxicity in a rabbit model of subretinal hemorrhage (SRH) and to assess intravitreal triamcinolone acetonide (IVTA) for anti-apoptotic and neuroprotective effects.
   METHODS. In adult rabbits, eyes were studied histologically after subretinal injection of autologous blood. For comparisons of control eyes with eyes injected with 2 mg IVTA, morphometric analysis was performed with light microscopy, whereas apoptosis was quantified with terminal dUTP nick end labeling (TUNEL) and fluorescence microscopy. Localization of retinal iron was assessed with Perls' stain.
   RESULTS. Photoreceptor degeneration was initiated 48 hours after exposure to subretinal blood and progressed over 7 days. Increased TUNEL positivity demonstrating apoptotic cell death was associated with SRH and photoreceptor loss. VIP-Perls staining demonstrated iron in the photoreceptor layer and retinal pigment epithelium that correlated with photoreceptor degeneration. Treatment with IVTA enhanced photoreceptor cell survival by 11% at 48 hours and by 45% at 72 hours (P = 0.01) and reduced photoreceptor apoptosis ratios by 25% at 48 hours (P = 0.006).
   CONCLUSIONS. Photoreceptor toxicity caused by SRH occurs at least in part by apoptosis and is associated with iron migration to the photoreceptor layer. Treatment with IVTA reduced photoreceptor loss and apoptosis, indicating a neuroprotective action. Therapies to target SRH may augment anti-VEGF treatments in exudative age-related macular degeneration and other diseases of choroidal neovascularization.
C1 [Bhisitkul, Robert B.; Winn, Bryan J.; Lee, On-Tat; Wong, Joshua; Pereira, Daniel de Souza] Univ Calif San Francisco, Sch Med, Dept Ophthalmol, San Francisco, CA 94143 USA.
   [Porco, Travis C.] Univ Calif San Francisco, Sch Med, Francis I Proctor Fdn, Epidemiol & Biostat Div, San Francisco, CA 94143 USA.
   [He, Xining; Hahn, Paul; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
C3 University of California System; University of California San Francisco;
   University of California System; University of California San Francisco;
   University of Pennsylvania; Pennsylvania Medicine
RP Bhisitkul, RB (通讯作者)，Univ Calif San Francisco, Sch Med, Dept Ophthalmol, 10 Koret Way,K301, San Francisco, CA 94143 USA.
EM bhisitkulr@vision.ucsf.edu
OI Hahn, Paul/0000-0002-6574-388X
FU Research to Prevent Blindness Foundation; That Man May See Foundation;
   National Institutes of Health [EY002162]; NATIONAL EYE INSTITUTE
   [P30EY002162] Funding Source: NIH RePORTER
FX Supported by Research to Prevent Blindness Foundation, That Man May See
   Foundation, and National Institutes of Health Grant EY002162.
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NR 52
TC 62
Z9 63
U1 0
U2 1
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 SEP
PY 2008
VL 49
IS 9
BP 4071
EP 4077
DI 10.1167/iovs.08-1892
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 344AB
UT WOS:000258896500046
PM 18421081
DA 2022-11-30
ER

PT J
AU Falkenstein, IA
   Cheng, L
   Freeman, WR
AF Falkenstein, Iryna A.
   Cheng, Lingyun
   Freeman, William R.
TI Changes of intraocular pressure after intravitreal injection of
   bevacizumab (Avastin)
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; bevacizumab (Avastin); intraocular
   pressure
ID TRIAMCINOLONE ACETONIDE; TRABECULAR MESHWORK; EYES; PEGAPTANIB;
   SECONDARY
AB Purpose: To determine changes and need to monitor intraocular pressure (IOP) following intravitreal injection of bevacizurnab (Avastin).
   Methods: Seventy patients (122 injections) underwent an intravitreal injection of Avastin for exudative age-related macular degeneration treatment. Forty-one eyes (59%) had single injection, 29 eyes (41 %) had repeated injections. IOP was measured before and after Avastin injection at 3, 10, and 15 minutes. Twenty-nine eyes were evaluated for baseline IOP changes after multiple injections. Statistical analysis was performed.
   Results: Baseline mean IOP was 15.17 +/- 3.42 mm Hg, with range from 08 mm Hg to 23 mm Hg. Postinjection 3 minutes the IOP had risen to a mean of 36.27 +/- 5.1 mm Hg and fell spontaneously to a mean of 24.56 +/- 5.9 mm Hg at 10 minutes. Ten eyes (14%) needed 15 minutes to drop below 30 mm Hg. All eyes were below 30 mm Hg at 15 minutes. No significant change between multiple baseline IOP measurements was detected.
   Conclusion: Avastin injections caused a predictable probably volume-related rise in IOP which never occluded the central retinal artery and which spontaneously fell to below 30 mm Hg in all eyes within 15 minutes. This strong safety profile provides guidelines on monitoring IOP after Avastin injections. There was no IOP change after multiple injections.
C1 Univ Calif San Diego, Joan & Irwin Jacobs Retina Ctr, Dept Ophthalmol, Shiley Eye Ctr, La Jolla, CA 92037 USA.
C3 University of California System; University of California San Diego
RP Freeman, WR (通讯作者)，Univ Calif San Diego, Joan & Irwin Jacobs Retina Ctr, Dept Ophthalmol, Shiley Eye Ctr, 9415 Campus Point Dr, La Jolla, CA 92037 USA.
EM freeman@eyeeenter.ucsd.edu
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NR 17
TC 102
Z9 111
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 OCT
PY 2007
VL 27
IS 8
BP 1044
EP 1047
DI 10.1097/IAE.0b013e3180592ba6
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 225DD
UT WOS:000250496400008
PM 18040242
DA 2022-11-30
ER

PT J
AU Malek, G
   Johnson, LV
   Mace, BE
   Saloupis, P
   Schmechel, DE
   Rickman, DW
   Toth, CA
   Sullivan, PM
   Rickman, CB
AF Malek, G
   Johnson, LV
   Mace, BE
   Saloupis, P
   Schmechel, DE
   Rickman, DW
   Toth, CA
   Sullivan, PM
   Rickman, CB
TI Apolipoprotein E allele-dependent pathogenesis: A model for age-related
   retinal degeneration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE amyloid choroidal neovascularization; macula; retinal pigment
   epithelium; cholesterol
ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-H POLYMORPHISM; PIGMENT EPITHELIUM;
   BRUCHS MEMBRANE; MACULAR DEGENERATION; ALZHEIMERS-DISEASE; ANIMAL-MODEL;
   DIETARY-FAT; E GENE; COMPLEMENT
AB Age-related macular degeneration (AMD) is a late-onset, multifactorial, neurodegenerative disease of the retina and the leading cause of irreversible vision loss in the elderly in the Western world. We describe here a murine model that combines three known AMD risk factors: advanced age, high fat cholesterol-rich (HF-C) diet, and apolipoprotein E (apoE) genotype. Eyes of aged, targeted replacement mice expressing human apoE2, apoE3, or apoE4 and maintained on a HF-C diet show apoE isoform-dependent pathologies of differential severity. ApoE4 mice are the most severely affected. They develop a constellation of changes that mimic the pathology associated with human AMD. These alterations include diffuse sub-retinal pigment epithelial deposits, drusenoid deposits, thickened Bruch's membrane, and atrophy, hypopigmentation, and hyperpigmentation of the retinal pigment epithelium. In extreme cases, apoE4 mice also develop marked choroidal neovascularization, a hallmark of exudative AMD. Neither age nor HF-C diet alone is sufficient to elicit these changes. We document choroidal neovascularization and other AMD-like ocular pathologies in an animal model that exploits known AMD risk factors. The model is additionally attractive because it is not complicated by invasive experimental intervention. Our findings in this model implicate the human apoE E4 allele as a susceptibility gene for AMD and support the hypothesis that common pathogenic mechanisms may underlie AMD and Alzheimer's disease.
C1 Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
   Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
   Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
   Duke Univ, Med Ctr, Dept Med, Div Neurol, Durham, NC 27710 USA.
   Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC 27710 USA.
   Univ Calif Santa Barbara, Neurosci Res Inst, Ctr Study Macular Degenerat, Santa Barbara, CA 93106 USA.
C3 Duke University; Duke University; Duke University; Duke University; Duke
   University; University of California System; University of California
   Santa Barbara
RP Rickman, CB (通讯作者)，Duke Univ, Med Ctr, Dept Ophthalmol, Box 3802, Durham, NC 27710 USA.
EM bowes007@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; Mace, Brian/0000-0002-5478-6227; Malek,
   Goldis/0000-0003-0026-2388
FU NATIONAL EYE INSTITUTE [R01EY011527, R01EY011286] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE ON AGING [P50AG005128] Funding Source: NIH
   RePORTER; NEI NIH HHS [P30EY0054722, R01 EY011527, R01 EY11286, R01
   EY011286, R01 EY11527] Funding Source: Medline; NIA NIH HHS [P50
   AG005128, P50 AG05128-20] Funding Source: Medline
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NR 58
TC 208
Z9 226
U1 1
U2 18
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 16
PY 2005
VL 102
IS 33
BP 11900
EP 11905
DI 10.1073/pnas.0503015102
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 956RH
UT WOS:000231317000059
PM 16079201
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Martins, TGD
   Schor, P
   Mendes, LGA
   Fowler, S
   Silva, R
AF Dos Santos Martins, Thiago Goncalves
   Schor, Paulo
   Arneiro Mendes, Luis Guilherme
   Fowler, Susan
   Silva, Rufino
TI Use of artificial intelligence in ophthalmology: a narrative review
SO SAO PAULO MEDICAL JOURNAL
LA English
DT Review
DE Artificial intelligence; Glaucoma; Retinopathy of prematurity;
   Ophthalmology
ID PLUS DISEASE DIAGNOSIS; MACULAR DEGENERATION; DIABETIC-RETINOPATHY;
   RETINAL IMAGES; PREMATURITY; VALIDATION; GLAUCOMA; SYSTEM
AB BACKGROUND: Artificial intelligence (AI) deals with development of algorithms that seek to perceive one's environment and perform actions that maximize one's chance of successfully reaching one's prede-termined goals.OBJECTIVE: To provide an overview of the basic principles of AI and its main studies in the fields of glau-coma, retinopathy of prematurity, age-related macular degeneration and diabetic retinopathy. From this perspective, the limitations and potential challenges that have accompanied the implementation and development of this new technology within ophthalmology are presented.DESIGN AND SETTING: Narrative review developed by a research group at the Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo (SP), Brazil.METHODS: We searched the literature on the main applications of AI within ophthalmology, using the keywords "artificial intelligence", "diabetic retinopathy", "macular degeneration age-related", "glaucoma" and "retinopathy of prematurity," covering the period from January 1, 2007, to May 3, 2021. We used the MED -LINE database (via PubMed) and the LILACS database (via Virtual Health Library) to identify relevant articles.RESULTS: We retrieved 457 references, of which 47 were considered eligible for intensive review and crit-ical analysis.CONCLUSION: Use of technology, as embodied in AI algorithms, is a way of providing an increasingly accurate service and enhancing scientific research. This forms a source of complement and innovation in relation to the daily skills of ophthalmologists. Thus, AI adds technology to human expertise.
C1 [Dos Santos Martins, Thiago Goncalves; Schor, Paulo] Univ Fed Sao Paulo UNIFESP, Dept Ophthalmol, R Botucatu 821, BR-04023062 Sao Paulo, SP, Brazil.
   [Silva, Rufino] Univ Coimbra, Fac Med, Coimbra Inst Clin & Biomed Res iCBR, Coimbra, Portugal.
C3 Universidade Federal de Sao Paulo (UNIFESP); Universidade de Coimbra
RP Martins, TGD (通讯作者)，Univ Fed Sao Paulo UNIFESP, Dept Ophthalmol, R Botucatu 821, BR-04023062 Sao Paulo, SP, Brazil.
RI ; Schor, Paulo/C-6555-2012
OI Mendes, Luis/0000-0002-3432-3604; Silva, Rufino/0000-0001-8676-0833;
   Schor, Paulo/0000-0002-3999-4706; Goncalves dos Santos Martins,
   Thiago/0000-0002-3878-8564
FU Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil
   (CAPES);  [001]
FX This study was financed in part by the Coordenacao de Aperfeicoamento de
   Pessoal de Nivel Superior-Brasil (CAPES) , under finance code 001
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NR 55
TC 0
Z9 0
U1 0
U2 0
PU ASSOCIACAO PAULISTA MEDICINA
PI SAO PAULO
PA AV BRIG LUIS ANTONIO, 278-7 ANDAR, SAO PAULO, CEP01318-901, BRAZIL
SN 1516-3180
J9 SAO PAULO MED J
JI Sao Paulo Med. J.
PD NOV-DEC
PY 2022
VL 140
IS 6
BP 837
EP 845
DI 10.1590/1516-3180.2021.0713.R1.22022022
PG 9
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 6G9UN
UT WOS:000885096700001
PM 36043665
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Brinks, J
   van Dijk, EHC
   Klaassen, I
   Schlingemann, RO
   Kielbasa, SM
   Emri, E
   Quax, PHA
   Bergen, AA
   Meijer, OC
   Boon, CJF
AF Brinks, J.
   van Dijk, E. H. C.
   Klaassen, I
   Schlingemann, R. O.
   Kielbasa, S. M.
   Emri, E.
   Quax, P. H. A.
   Bergen, A. A.
   Meijer, O. C.
   Boon, C. J. F.
TI Exploring the choroidal vascular labyrinth and its molecular and
   structural roles in health and disease
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Choroid; Choroidal endothelial cell; Chorioretinal disease;
   Fenestrations; Vascular endothelial growth factor
ID CENTRAL SEROUS CHORIORETINOPATHY; OPTICAL COHERENCE TOMOGRAPHY;
   ENDOTHELIAL GROWTH-FACTOR; COMPLEMENT FACTOR-H; RETINAL-PIGMENT
   EPITHELIUM; INDOCYANINE GREEN ANGIOGRAPHY; INCLUDING FLOW
   DETERMINATIONS; PUNCTATE INNER CHOROIDOPATHY; BRUCHS MEMBRANE
   IMPLICATIONS; VESICLE-ASSOCIATED PROTEIN
AB The choroid is a key player in maintaining ocular homeostasis and plays a role in a variety of chorioretinal diseases, many of which are poorly understood. Recent advances in the field of single-cell RNA sequencing have yielded valuable insights into the properties of choroidal endothelial cells (CECs). Here, we review the role of the choroid in various physiological and pathophysiological mechanisms, focusing on the role of CECs. We also discuss new insights regarding the phenotypic properties of CECs, CEC subpopulations, and the value of measuring transcriptomics in primary CEC cultures derived from post-mortem eyes. In addition, we discuss key phenotypic, structural, and functional differences that distinguish CECs from other endothelial cells such as retinal vascular endothelial cells. Understanding the specific clinical and molecular properties of the choroid will shed new light on the pathogenesis of the broad clinical range of chorioretinal diseases such as age-related macular degeneration, central serous chorioretinopathy and other diseases within the pachychoroid spectrum, uveitis, and diabetic choroidopathy. Although our knowledge is still relatively limited with respect to the clinical features and molecular pathways that underlie these chorioretinal diseases, we summarise new approaches and discuss future directions for gaining new insights into these sight-threatening diseases and highlight new therapeutic strategies such as pluripotent stem cell-based technologies and gene therapy.
C1 [Brinks, J.; van Dijk, E. H. C.; Boon, C. J. F.] Leiden Univ Med Ctr, Dept Ophthalmol, Leiden, Netherlands.
   [Klaassen, I; Schlingemann, R. O.] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Ophthalmol, Ocular Angiogenesis Grp, Amsterdam, Netherlands.
   [Klaassen, I; Schlingemann, R. O.] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Biol, Ocular Angiogenesis Grp, Amsterdam, Netherlands.
   [Schlingemann, R. O.; Boon, C. J. F.] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Ophthalmol, Amsterdam, Netherlands.
   [Schlingemann, R. O.] Univ Lausanne, Jules Gonin Eye Hosp, Fdn Asile des Aveugles, Dept Ophthalmol, Lausanne, Switzerland.
   [Kielbasa, S. M.] Leiden Univ Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands.
   [Emri, E.; Bergen, A. A.] Amsterdam Univ Med Ctr, Dept Clin Genet, Sect Ophthalmogenet, Amsterdam, Netherlands.
   [Quax, P. H. A.] Leiden Univ Med Ctr, Dept Vasc Surg, Leiden, Netherlands.
   [Quax, P. H. A.] Leiden Univ Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands.
   [Meijer, O. C.] Leiden Univ Med Ctr, Dept Med, Div Endocrinol & Metab, Leiden, Netherlands.
C3 Leiden University; Leiden University Medical Center (LUMC); University
   of Amsterdam; University of Amsterdam; University of Amsterdam;
   University of Lausanne; Leiden University; Leiden University Medical
   Center (LUMC); Leiden University; Leiden University Medical Center
   (LUMC); Leiden University; Leiden University Medical Center (LUMC);
   Leiden University; Leiden University Medical Center (LUMC)
RP Boon, CJF (通讯作者)，Amsterdam Univ Med Ctr, Dept Ophthalmol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM camiel.boon@amsterdamumc.nl
OI Quax, Paul/0000-0002-6853-5760
FU Stichting Macula Fonds; Retina Nederland Onderzoek Fonds; Stichting
   BlindenPenning; Alge-mene Nederlandse Vereniging ter Voorkoming van
   Blindheid; Landelijke Stichting voor Blinden en Slechtzienden; UitZicht;
   Rotterdamse Stichting Blindenbelangen; Stichting Leids Oogheelkundig
   Ondersteuningsfonds; Stichting Blind-enhulp; Stichting Ooglijders; ZonMw
   MKMD Grant; IFER Graduate Fellowship Program; Health Holland PLURIMACULA
   Grant
FX Supported by the following foundations: Stichting Macula Fonds, Retina
   Nederland Onderzoek Fonds, Stichting BlindenPenning, Alge-mene
   Nederlandse Vereniging ter Voorkoming van Blindheid, and Landelijke
   Stichting voor Blinden en Slechtzienden, which contributed through
   UitZicht, as well as Rotterdamse Stichting Blindenbelangen, Stichting
   Leids Oogheelkundig Ondersteuningsfonds,Stichting Blind-enhulp,
   Stichting Ooglijders, ZonMw MKMD Grant, IFER Graduate Fellowship
   Program, and Health Holland PLURIMACULA Grant. The funding organisations
   had no role in the design or conduct of the study; collection,
   management, analysis, and interpretation of the data; preparation,
   review, or approval of the manuscript; and decision to submit the
   manuscript for publication. They provided unrestricted grants.
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NR 447
TC 12
Z9 12
U1 12
U2 15
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 2022
VL 87
AR 100994
DI 10.1016/j.preteyeres.2021.100994
PG 47
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 0J9US
UT WOS:000780444100001
PM 34280556
OA hybrid
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Sorenson, CM
   Farnoodian, M
   Wang, SJ
   Song, YS
   Darjatmoko, SR
   Polans, AS
   Sheibani, N
AF Sorenson, Christine M.
   Farnoodian, Mitra
   Wang, Shoujian
   Song, Yong-Seok
   Darjatmoko, Soesiawati R.
   Polans, Arthur S.
   Sheibani, Nader
TI Fingolimod (FTY720), a Sphinogosine-1-Phosphate Receptor Agonist,
   Mitigates Choroidal Endothelial Proangiogenic Properties and Choroidal
   Neovascularization
SO CELLS
LA English
DT Article
DE age-related macular degeneration; inflammation; choroid; retinal pigment
   epithelium; retinal vasculature; microglia
ID PROTEIN-COUPLED RECEPTOR; SPHINGOSINE-1-PHOSPHATE RECEPTORS; SPROUTING
   ANGIOGENESIS; CELLS; DEGENERATION; ATTENUATION; INHIBITION; EXPRESSION;
   MODEL; FORM
AB Neovascular or wet age-related macular degeneration (nAMD) causes vision loss due to inflammatory and vascular endothelial growth factor (VEGF)-driven neovascularization processes in the choroid. Due to the excess in VEGF levels associated with nAMD, anti-VEGF therapies are utilized for treatment. Unfortunately, not all patients have a sufficient response to such therapies, leaving few if any other treatment options for these patients. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator found in endothelial cells that participates in modulating barrier function, angiogenesis, and inflammation. S1P, through its receptor (S1PR1) in endothelial cells, prevents illegitimate sprouting angiogenesis during vascular development. In the present paper, we show that, in choroidal endothelial cells, S1PR1 is the most abundantly expressed S1P receptor and agonism of S1PR1-prevented choroidal endothelial cell capillary morphogenesis in culture. Given that nAMD pathogenesis draws from enhanced inflammation and angiogenesis as well as a loss of barrier function, we assessed the impact of S1PR agonism on choroidal neovascularization in vivo. Using laser photocoagulation rupture of Bruch's membrane to induce choroidal neovascularization, we show that S1PR non-selective (FTY720) and S1PR1 selective (CYM5442) agonists significantly inhibit choroidal neovascularization in this model. Thus, utilizing S1PR agonists to temper choroidal neovascularization presents an additional novel use for these agonists presently in clinical use for multiple sclerosis as well as other inflammatory diseases.
C1 [Sorenson, Christine M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53705 USA.
   [Sorenson, Christine M.; Darjatmoko, Soesiawati R.; Sheibani, Nader] Univ Wisconsin, Sch Med & Publ Hlth, McPherson Eye Res Inst, Madison, WI 53705 USA.
   [Farnoodian, Mitra; Wang, Shoujian; Song, Yong-Seok; Darjatmoko, Soesiawati R.; Polans, Arthur S.; Sheibani, Nader] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53705 USA.
   [Sheibani, Nader] Univ Wisconsin, Sch Med & Publ Hlth, Dept Cell & Regenerat Biol, Madison, WI 53705 USA.
   [Sheibani, Nader] Univ Wisconsin, Dept Biomed Engn, 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;
   University of Wisconsin System; University of Wisconsin Madison;
   University of Wisconsin System; University of Wisconsin Madison
RP Sheibani, N (通讯作者)，Univ Wisconsin, Sch Med & Publ Hlth, McPherson Eye Res Inst, Madison, WI 53705 USA.; Sheibani, N (通讯作者)，Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53705 USA.; Sheibani, N (通讯作者)，Univ Wisconsin, Sch Med & Publ Hlth, Dept Cell & Regenerat Biol, Madison, WI 53705 USA.; Sheibani, N (通讯作者)，Univ Wisconsin, Dept Biomed Engn, Madison, WI 53705 USA.
EM cnisorenson@pediatrics.wisc.edu; farnoodian@wisc.edu;
   shoujianwang@wisc.edu; song224@wisc.edu; srdarjat@wisc.edu;
   aspolans@wisc.edu; nsheibanikar@wisc.edu
OI Farnoodian, Mitra/0000-0001-6990-8111; Sheibani,
   Nader/0000-0003-2723-9217
FU Research to Prevent Blindness; Visual Sciences, Retina Research
   Foundation; RRF/Daniel M. Albert chair [P30 EY016665, P30 CA014520, R01
   EY026078, EY030076, EY030502, HL158073]
FX This work and/or the investigator(s) were supported by an unrestricted
   award from Research to Prevent Blindness to the Department of
   Ophthalmology and Visual Sciences, Retina Research Foundation,
   RRF/Daniel M. Albert chair, P30 EY016665, P30 CA014520, R01 EY026078,
   EY030076, EY030502, and HL158073.
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NR 46
TC 0
Z9 0
U1 0
U2 1
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD MAR
PY 2022
VL 11
IS 6
AR 969
DI 10.3390/cells11060969
PG 15
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 0E9LB
UT WOS:000776992600001
PM 35326420
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Park, HS
   Byun, Y
   Byeon, SH
   Kim, SS
   Kim, YJ
   Lee, CS
AF Park, Hyo Song
   Byun, Yeojue
   Byeon, Suk Ho
   Kim, Sung Soo
   Kim, Yong Joon
   Lee, Christopher Seungkyu
TI Retinal Hemorrhage after SARS-CoV-2 Vaccination
SO JOURNAL OF CLINICAL MEDICINE
LA English
DT Article
DE retinal vein occlusion; submacular hemorrhage; SARS-CoV-2; vaccine;
   ChAdOx1 nCoV-19; BNT162b2
ID MESSENGER-RNA; MYOCARDITIS; ASSOCIATION; INTERFERON; OCCLUSION; VEIN
AB To report retinal vein occlusion (RVO) and age-related macular degeneration (AMD)-related submacular hemorrhage developing after administration of SARS-CoV-2 vaccines, a single-center, retrospective observational case series was conducted. Clinical data including fundus photographs and optical coherence tomography (OCT) scans were reviewed. Twenty-three eyes of 21 patients were included with the median age at symptom presentation being 77 years (range: 51-85 years). Twelve eyes (52.2%) had submacular hemorrhage and 11 (47.8%) had RVO. Twelve patients (60.9%) had been vaccinated with the Pfizer vaccine (BNT162b2) and 8 with the AstraZeneca (ChAdOx1) vaccine. Sixteen patients (76.2%) experienced ocular disease exacerbation after the first vaccination and 4 (19.0%) after the second vaccination. The median visual acuity (logarithm of the minimal angle of resolution; logMAR) before symptom development was 0.76 (interquartile range: 0.27-1.23); the median logMAR at symptom presentation was 1.40 (interquartile range 0.52-1.70). The median time between vaccination and symptom exacerbation was 2.0 days (interquartile range: 1.0-3.0 days). Five patients (23.8%) underwent tests for hematological abnormalities, including the presence of anti-PF4 antibodies; all were negative. Further studies with larger patient group for evaluation of effect of SARS-CoV-2 vaccination on retinal hemorrhage are necessary.
C1 [Park, Hyo Song; Byeon, Suk Ho; Kim, Sung Soo; Kim, Yong Joon; Lee, Christopher Seungkyu] Yonsei Univ, Inst Vis Res, Severance Hosp, Coll Med,Dept Ophthalmol, Seoul 03772, South Korea.
   [Byun, Yeojue] Kong Eye Clin, Seoul 03157, South Korea.
C3 Yonsei University; Yonsei University Health System
RP Kim, YJ; Lee, CS (通讯作者)，Yonsei Univ, Inst Vis Res, Severance Hosp, Coll Med,Dept Ophthalmol, Seoul 03772, South Korea.
EM hyosong@yuhs.ac; yeojue@naver.com; SHBYEON@yuhs.ac; SEMEKIM@yuhs.ac;
   kyjcolor@naver.com; sklee219@yuhs.ac
OI Park, Hyo Song/0000-0002-0534-2558; Byeon, suk ho/0000-0001-8101-0830;
   Lee, Christopher/0000-0001-5054-9470; Kim, Sung Soo/0000-0002-0574-7993
FU Basic Science Research Program through the National Research Foundation
   of Korea [2019R1A2C2002393]
FX FundingThis research was supported by the Basic Science Research Program
   through the National Research Foundation of Korea under 2019R1A2C2002393
   (CSL). The funding organization had no role in the design or conduct of
   this research.
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NR 32
TC 5
Z9 5
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2077-0383
J9 J CLIN MED
JI J. Clin. Med.
PD DEC
PY 2021
VL 10
IS 23
AR 5705
DI 10.3390/jcm10235705
PG 13
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA YC5AI
UT WOS:000739703800001
PM 34884407
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Schlecht, A
   Thien, A
   Wolf, J
   Prinz, G
   Agostini, H
   Schlunck, G
   Wieghofer, P
   Boneva, S
   Lange, C
AF Schlecht, Anja
   Thien, Adrian
   Wolf, Julian
   Prinz, Gabriele
   Agostini, Hansjuergen
   Schlunck, Guenther
   Wieghofer, Peter
   Boneva, Stefaniya
   Lange, Clemens
TI Immunosenescence in Choroidal Neovascularization (CNV)-Transcriptional
   Profiling of Naive and CNV-Associated Retinal Myeloid Cells during Aging
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration (AMD); choroidal neovascularization
   (CNV); aging; immunosenescence; microglia; myeloid cells; RNA-sequencing
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; VISUAL IMPAIRMENT; 5-YEAR
   INCIDENCE; MACROPHAGES; PREVALENCE; EYES; ACCUMULATION; OSTEOPONTIN;
   EXPRESSION
AB Immunosenescence is considered a possible factor in the development of age-related macular degeneration and choroidal neovascularization (CNV). However, age-related changes of myeloid cells (MCs), such as microglia and macrophages, in the healthy retina or during CNV formation are ill-defined. In this study, Cx3cr1-positive MCs were isolated by fluorescence-activated cell sorting from six-week (young) and two-year-old (old) Cx3cr1(GFP)(/+) mice, both during physiological aging and laser-induced CNV development. High-throughput RNA-sequencing was performed to define the age-dependent transcriptional differences in MCs during physiological aging and CNV development, complemented by immunohistochemical characterization and the quantification of MCs, as well as CNV size measurements. These analyses revealed that myeloid cells change their transcriptional profile during both aging and CNV development. In the steady state, senescent MCs demonstrated an upregulation of factors contributing to cell proliferation and chemotaxis, such as Cxcl13 and Cxcl14, as well as the downregulation of microglial signature genes. During CNV formation, aged myeloid cells revealed a significant upregulation of angiogenic factors such as Arg1 and Lrg1 concomitant with significantly enlarged CNV and an increased accumulation of MCs in aged mice in comparison to young mice. Future studies need to clarify whether this observation is an epiphenomenon or a causal relationship to determine the role of immunosenescence in CNV formation.
C1 [Schlecht, Anja] Julius Maximilians Univ Wuerzburg, Inst Anat & Cell Biol, D-97070 Wurzburg, Germany.
   [Schlecht, Anja; Thien, Adrian; Wolf, Julian; Prinz, Gabriele; Agostini, Hansjuergen; Schlunck, Guenther; Boneva, Stefaniya; Lange, Clemens] Univ Freiburg, Ctr Eye, Med Ctr, Fac Med, D-79106 Freiburg, Germany.
   [Wieghofer, Peter] Univ Leipzig, Inst Anat, D-04103 Leipzig, Germany.
   [Wieghofer, Peter] Univ Augsburg, Inst Theoret Med, Med Fac, Cellular Neuroanat, D-86159 Augsburg, Germany.
C3 University of Wurzburg; University of Freiburg; Leipzig University;
   University of Augsburg
RP Schlecht, A (通讯作者)，Julius Maximilians Univ Wuerzburg, Inst Anat & Cell Biol, D-97070 Wurzburg, Germany.; Schlecht, A; Lange, C (通讯作者)，Univ Freiburg, Ctr Eye, Med Ctr, Fac Med, D-79106 Freiburg, Germany.
EM Anja.schlecht@uni-wuerzburg.de; adrian.thien@uniklinik-freiburg.de;
   julian.wolf@uniklinik-freiburg.de; gabriele.prinz@uniklinik-freiburg.de;
   hansjuergen.agostini@uniklinik-freiburg.de;
   guenther.schlunck@uniklinik-freiburg.de;
   peter.wieghofer@medizin.uni-leipzig.de;
   Stefaniya.boneva@uniklinik-freiburg.de;
   Clemens.lange@uniklinik-freiburg.de
RI Wieghofer, Peter/AAV-9572-2020
OI Boneva, Stefaniya/0000-0002-9811-2160; Wieghofer,
   Peter/0000-0003-4959-1182; Wolf, Julian/0000-0002-3470-9697
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NR 75
TC 4
Z9 4
U1 2
U2 4
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 DEC
PY 2021
VL 22
IS 24
AR 13318
DI 10.3390/ijms222413318
PG 15
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA XZ8DQ
UT WOS:000737878100001
PM 34948115
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Dutt, S
   Sivaraman, A
   Savoy, F
   Rajalakshmi, R
AF Dutt, Sreetama
   Sivaraman, Anand
   Savoy, Florian
   Rajalakshmi, Ramachandran
TI Insights into the growing popularity of artificial intelligence in
   ophthalmology
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE Age-related macular degeneration; anterior-segment diseases; artificial
   intelligence; cataract; deep learning; diabetic retinopathy; glaucoma;
   machine learning; ophthalmology; retinopathy of prematurity
ID DIABETIC-RETINOPATHY; AUTOMATED DETECTION; MACULAR DEGENERATION; RETINAL
   IMAGES; PLUS DISEASE; PREMATURITY; VALIDATION
AB Artificial intelligence (AI) in healthcare is the use of computer-algorithms in analyzing complex medical data to detect associations and provide diagnostic support outputs. AI and deep learning (DL) find obvious applications in fields like ophthalmology wherein huge amount of image-based data need to be analyzed; however, the outcomes related to image recognition are reasonably well-defined. AI and DL have found important roles in ophthalmology in early screening and detection of conditions such as diabetic retinopathy (DR), age-related macular degeneration (ARMD), retinopathy of prematurity (ROP), glaucoma, and other ocular disorders, being successful inroads as far as early screening and diagnosis are concerned and appear promising with advantages of high-screening accuracy, consistency, and scalability. AI algorithms need equally skilled manpower, trained optometrists/ophthalmologists (annotators) to provide accurate ground truth for training the images. The basis of diagnoses made by AI algorithms is mechanical, and some amount of human intervention is necessary for further interpretations. This review was conducted after tracing the history of AI in ophthalmology across multiple research databases and aims to summarise the journey of AI in ophthalmology so far, making a close observation of most of the crucial studies conducted. This article further aims to highlight the potential impact of AI in ophthalmology, the pitfalls, and how to optimally use it to the maximum benefits of the ophthalmologists, the healthcare systems and the patients, alike.
C1 [Dutt, Sreetama; Sivaraman, Anand] Remidio Innovat Solut, Dept Res & Dev, Bengaluru, Karnataka, India.
   [Savoy, Florian] Madras Diabet Res Fdn, Dr Mohans Diabet Special Ctr, Dept Ophthalmol, Chennai, Tamil Nadu, India.
   [Rajalakshmi, Ramachandran] Medios Technol, Dept Artificial Intelligence, Singapore, Singapore.
C3 Madras Diabetes Research Foundation
RP Rajalakshmi, R (通讯作者)，Dr Mohans Diabet Special Ctr, Dept Ophthalmol, 6 Conran Smith Rd, Chennai 600086, Tamil Nadu, India.; Rajalakshmi, R (通讯作者)，Madras Diabet Res Fdn, Dept Ophthalmol, 6 Conran Smith Rd, Chennai 600086, Tamil Nadu, India.
EM drraj@drmohans.com
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NR 38
TC 10
Z9 10
U1 6
U2 18
PU WOLTERS KLUWER MEDKNOW PUBLICATIONS
PI MUMBAI
PA WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S  NO 1498A-2
   VILLAGE MAROL, ANDHERI EAST, MUMBAI, 400059, INDIA
SN 0301-4738
EI 1998-3689
J9 INDIAN J OPHTHALMOL
JI Indian J. Ophthalmol.
PD JUL
PY 2020
VL 68
IS 7
BP 1339
EP +
DI 10.4103/ijo.IJO_1754_19
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MG4YE
UT WOS:000546038300022
PM 32587159
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Invernizzi, A
   Pellegrini, M
   Cornish, E
   Teo, KYC
   Cereda, M
   Chabblani, J
AF Invernizzi, Alessandro
   Pellegrini, Marco
   Cornish, Elisa
   Teo, Kelvin Yi Chong
   Cereda, Matteo
   Chabblani, Jay
TI Imaging the Choroid: From Indocyanine Green Angiography to Optical
   Coherence Tomography Angiography
SO ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE angiography; choroid; imaging; indocyanine green; optical coherence
   tomography
ID RETINAL VEIN OCCLUSION; DIABETIC-RETINOPATHY; PANRETINAL
   PHOTOCOAGULATION; RETINITIS-PIGMENTOSA; LEUKOCYTE DYNAMICS;
   STRUCTURAL-CHANGES; VASCULARITY INDEX; MACULAR EDEMA; DARK ATROPHY;
   THICKNESS
AB The choroid is the vascular structure nourishing the retinal pigment epithelium and the outer retina and it plays a key role in the homeostasis of the eye both under physiological and pathological conditions. In the last 20 years we have moved from "guessing" what was happening beyond the retinal pigment epithelium to actually visualize structural and functional changes of the choroid in vivo noninvasively. In this review we describe the state of the art of choroidal imaging, focusing on the multiple techniques available in the clinical and research setting including indocyanine green angiography, labeled-cells angiographies, optical coherence tomography (OCT), enhanced depth imaging, swept source OCT, and OCT angiography. In the first section of the article, we describe their main applications and the basic principles to interpret the imaging results. Increasing evidence suggests that the choroid is much more involved than we used to think in many pathological conditions from uveitis to intraocular tumors, from vascular diseases to age-related macular degeneration. All clinicians should hence know which is the most appropriate imaging investigation to explore the choroid in the disease they are dealing with and how to interpret the results. For this reason the second section of this review summarizes the best imaging approach and the most common findings visible on choroidal imaging in different diseases of the eye.
C1 [Invernizzi, Alessandro; Pellegrini, Marco; Cereda, Matteo] Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Eye Clin, Milan, Italy.
   [Invernizzi, Alessandro; Cornish, Elisa; Teo, Kelvin Yi Chong] Univ Sydney, Save Sight Inst, Sydney Med Sch, Discipline Ophthalmol, Sydney, NSW, Australia.
   [Teo, Kelvin Yi Chong] Singapore Natl Eye Ctr, Singapore, Singapore.
   [Teo, Kelvin Yi Chong] Singapore Eye Res Inst, Singapore, Singapore.
   [Chabblani, Jay] Univ Pittsburgh, Dept Ophthalmol, Med Ctr, Pittsburgh, PA 15260 USA.
C3 University of Milan; Luigi Sacco Hospital; University of Sydney;
   Singapore National Eye Center; National University of Singapore;
   Singapore National Eye Center; Pennsylvania Commonwealth System of
   Higher Education (PCSHE); University of Pittsburgh
RP Invernizzi, A (通讯作者)，L Sacco Hosp Univ Milan, Dept Biomed & Clin Sci, Eye Clin, Via GB Grassi 74, I-20157 Milan, Italy.
EM alessandro.invernizzi@gmail.com
OI Teo, Kelvin/0000-0002-7458-7081
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NR 102
TC 18
Z9 18
U1 1
U2 2
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 JUL-AUG
PY 2020
VL 9
IS 4
BP 335
EP 348
DI 10.1097/APO.0000000000000307
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MX2GL
UT WOS:000557544400009
PM 32739938
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Gour, N
   Khanna, P
AF Gour, Neha
   Khanna, Pritee
TI Speckle denoising in optical coherence tomography images using residual
   deep convolutional neural network
SO MULTIMEDIA TOOLS AND APPLICATIONS
LA English
DT Article
DE Speckle denoising; Optical coherence tomography; Convolutional neural
   network; Residual network; Ocular disease diagnosis
ID NOISE-REDUCTION; ANISOTROPIC DIFFUSION; ALGORITHM; SPARSE
AB Optical Coherence Tomography (OCT) is an emerging imaging modality used for diagnosis of ocular diseases like age-related macular degeneration (AMD) and macular edema. OCT imaging is a non-invasive technique to capture cross-sectional volumes of the retinal areas of human eye. Due to coherent nature of image acquisition process, OCT images suffer from granular multiplicative speckle noise. Presence of speckle noise in OCT images makes its clinical analysis difficult for the experts. The same is the problem with the development of computer aided diagnosis (CAD) systems for detection of ocular diseases. Speckle noise is granular in nature and interferes with the diagnostic observations made using OCT images and the segmentation of different OCT layers. This work presents an efficient OCT denoising technique using residual convolutional neural network. The proposed technique will not only help experts in analysis of OCT images, but can also act as first step to construct CAD systems for ocular diseases. The performance of the proposed approach is evaluated on Duke (SD-OCT) and Topcon (3D-OCT) image databases based on visual and parametric observations. The performance of the proposed method on parameters like PSNR, SSIM, MSR, CNR, and ENL is compared with the state-of-the-art speckle denoising methods. It is observed that the proposed approach performs better as compared to the methods referred from literature on both visual and parametric evaluations.
C1 [Gour, Neha; Khanna, Pritee] PDPM Indian Inst Informat Technol Design & Mfg, Jabalpur, India.
C3 Indian Institute of Information Technology Design & Manufacturing,
   Jabalpur
RP Gour, N (通讯作者)，PDPM Indian Inst Informat Technol Design & Mfg, Jabalpur, India.
EM g.neha@iiitdmj.ac.in; pkhanna@iiitdmj.ac.in
RI Khanna, Pritee/V-5418-2019
OI Khanna, Pritee/0000-0003-0518-2133
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NR 57
TC 9
Z9 9
U1 4
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1380-7501
EI 1573-7721
J9 MULTIMED TOOLS APPL
JI Multimed. Tools Appl.
PD JUN
PY 2020
VL 79
IS 21-22
BP 15679
EP 15695
DI 10.1007/s11042-019-07999-y
PG 17
WC Computer Science, Information Systems; Computer Science, Software
   Engineering; Computer Science, Theory & Methods; Engineering, Electrical
   & Electronic
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering
GA LV8HQ
UT WOS:000538675900071
DA 2022-11-30
ER

PT J
AU Yan, JZ
   Qin, YH
   Yu, JS
   Peng, QH
   Chen, XD
AF Yan, Jiazhao
   Qin, Yuhui
   Yu, Jingsheng
   Peng, Qinghua
   Chen, Xiangdong
TI MiR-340/iASPP axis affects UVB-mediated retinal pigment epithelium (RPE)
   cell damage
SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
LA English
DT Article
DE Ultraviolet B (UVB); Retinal pigment epithelium (RPE) cell; Apoptosis;
   iASPP; miR-340; Light damage
ID HUMAN DERMAL FIBROBLASTS; ARPE19 CELLS; ULTRAVIOLET-RADIATION; INDUCED
   APOPTOSIS; OXIDATIVE STRESS; HACAT CELLS; EXPRESSION; MICRORNAS;
   CARCINOMA; IASPP
AB Long-term exposure to ultraviolet B (UVB) light increases the risk of UVB damage due to increased UVB absorption by the retina and may further lead to age-related eye diseases. The retinal pigment epithelium (RPE) cell is a main target of UVB reaching the retina; its degeneration is an essential event in UVB-mediated age-related macular degeneration (AMD). Herein, we first evaluated the expression and effect of iASPP, an inhibitory regulator of apoptosis, in UVB-induced RPE cell damage. Through the mechanism of RNA interference at the post-transcriptional level, miRNA affects a variety of cellular processes, including UVB-mediated cell damage. We next screened for upstream candidate miRNAs that may regulate iASPP expression. Among 8 candidate miRNAs, UVB significantly increased miR-340 levels. We also confirmed the direct binding of miR-340 to the 3'UTR of iASPP, and assessed the combined effect of miR-340 and iASPP on UVB-induced RPE cell damage. Taken together, we demonstrated the possible mechanisms involved in UVB-induced retinal damage. In RPE cells, UVB irradiation inhibits iASPP expression through inducing miR-340 expression, thereby promoting RPE cell apoptosis and suppressing cell viability via affecting p53, p21 and caspase-3 protein expression. Targeting miR-340 to rescue iASPP expression in RPE cells may help treat UVB-mediated retinal damage.
C1 [Yan, Jiazhao; Qin, Yuhui] Hunan Univ Chinese Med, Coll Tradit Chinese Med 1, Changsha 410208, Hunan, Peoples R China.
   [Yan, Jiazhao; Yu, Jingsheng; Peng, Qinghua; Chen, Xiangdong] Hunan Univ Chinese Med, Hosp 1, Dept Ophthalmol, Changsha 410007, Hunan, Peoples R China.
C3 Hunan University of Chinese Medicine; Hunan University of Chinese
   Medicine
RP Qin, YH (通讯作者)，Hunan Univ Chinese Med, Hanpu Sci & Technol Pk, Changsha 410208, Hunan, Peoples R China.
EM dlqyh@sohu.com
FU National Natural Science Foundation of China [81303007]
FX This study was supported by National Natural Science Foundation of China
   (No. 81303007).
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NR 37
TC 12
Z9 12
U1 3
U2 13
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 1011-1344
J9 J PHOTOCH PHOTOBIO B
JI J. Photochem. Photobiol. B-Biol.
PD SEP
PY 2018
VL 186
BP 9
EP 16
DI 10.1016/j.jphotobiol.2018.04.005
PG 8
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA GS4ZA
UT WOS:000443665200002
PM 29982095
DA 2022-11-30
ER

PT J
AU Luttrull, JK
   Sinclair, SH
   Elmann, S
   Glaser, BM
AF Luttrull, Jeffrey K.
   Sinclair, Stephen H.
   Elmann, Solly
   Glaser, Bert M.
TI Low incidence of choroidal neovascularization following subthreshold
   diode micropulse laser (SDM) in high-risk AMD
SO PLOS ONE
LA English
DT Article
ID DIABETIC MACULAR EDEMA; HEAT-SHOCK PROTEINS; DEGENERATION; EYE;
   PHOTOCOAGULATION; PROGRESSION; BURDEN; METAANALYSIS; EXPRESSION;
   RESPONSES
AB Purpose
   To determine the incidence of new choroidal neovascularization (CNV) in eyes with dry age-related macular degeneration (AMD) following subthreshold diode micropulse laser (SDM).
   Method
   In an observational retrospective cohort study, the records of all patients active in the electronic medical records database were reviewed to identify eyes with dry AMD treated with SDM. Identified eyes were classified by simplified AREDS categories, and analyzed for the primary endpoint of new CNV after treatment.
   Results
   The EMR revealed SDM was offered to 373/392 (95%) patients with dry AMD and elected by 363/373 (97%) between 2008-2017. Follow up was available for 354/363 patients (547 eyes, 98%) (range 6-108 mos., avg. 22). CNV risk factors included age (median 84 years, 67%> 80); reticular pseudodrusen (214 eyes, 39%); AREDS category (78% category 3 and 4); and fellow eye CNV (128 eyes, 23%). New CNV developed in 9/547 eyes (1.6%, annualized rate 0.87%). Visual acuity was unchanged. There were no adverse treatment effects.
   Summary
   In a review of a large group of eyes with exceptionally high-risk AMD, SDM was followed by a very low incidence of new CNV. If confirmed by further study, SDM would offer a new and highly effective treatment to reduce the risk of vision loss from AMD.
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   [Elmann, Solly; Glaser, Bert M.] Natl Retina Inst, Towson, MD USA.
C3 Drexel University
EM office@venturacountyretina.com
OI Luttrull, Jeffrey K/0000-0002-4475-3237
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NR 67
TC 10
Z9 10
U1 2
U2 2
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 23
PY 2018
VL 13
IS 8
AR e0202097
DI 10.1371/journal.pone.0202097
PG 16
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GR6TZ
UT WOS:000442800100039
PM 30138455
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Hulleman, JD
   Brown, SJ
   Rosen, H
   Kelly, JW
AF Hulleman, John D.
   Brown, Steven J.
   Rosen, Hugh
   Kelly, Jeffery W.
TI A High-Throughput Cell-Based Gaussia Luciferase Reporter Assay for
   Identifying Modulators of Fibulin-3 Secretion
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE fibulin-3; Gaussia luciferase; Malattia Leventinese; high-throughput
   chemical screening; LOPAC; fibulin-3-dependent gliomas
ID ABERRANT ACCUMULATION; EFEMP1; ACTIVATION; EXPRESSION; GENE; DEPOSITS;
   MUTATION; CULTURE; ALTERS
AB An R345W mutation in fibulin-3 causes its inefficient secretion, increased intracellular steady-state levels, and the macular dystrophy, Malattia Leventinese (ML), a disease similar to age-related macular degeneration. It is unknown whether R345W causes ML through increased intracellular levels, by the secretion of a potentially aggregation-prone protein, or both. To identify small molecules that alter the secretion of fibulin-3, we developed ARPE19 retinal cell lines that inducibly express wild-type (WT) or R345W fibulin-3 fused to an enhanced Gaussia luciferase (eGLuc2). Screening of the Library of Pharmacologically Active Compounds demonstrated that these cell lines and the GLuc assay are suitable for high-throughput chemical screening. Two estrogen-related compounds enhanced fibulin-3 secretion, whereas a diverse series of small molecules reduced fibulin-3 secretion. A counterscreen identified compounds that did not substantially alter the secretion of unfused eGLuc2, demonstrating at least partial selectivity for fibulin-3. A secondary assay using untagged fibulin-3 confirmed that the top three inhibitory compounds reduced R345W fibulin-3 secretion. Interestingly, in untagged fibulin-3 studies, one compound, phorbol 12-myristate 13-acetate, reduced R345W fibulin-3 secretion while minimally enhancing WT fibulin-3 secretion, the desired activity and selectivity we sought for ML. The identified compounds could serve as tools for probing the etiology of fibulin-3-related diseases.
C1 [Hulleman, John D.; Kelly, Jeffery W.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Hulleman, John D.; Kelly, Jeffery W.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
   [Hulleman, John D.; Kelly, Jeffery W.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA.
   [Brown, Steven J.; Rosen, Hugh] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
C3 Scripps Research Institute; Scripps Research Institute; Scripps Research
   Institute; Scripps Research Institute
RP Hulleman, JD (通讯作者)，Scripps Res Inst, 10550 N Torrey Pines Rd,MEM 230, La Jolla, CA 92037 USA.
EM hulleman@scripps.edu; jkelly@scripps.edu
RI Hulleman, John D./AAV-8242-2020
OI Hulleman, John/0000-0001-8149-656X
FU Lita Annenberg Hazen Foundation; Skaggs Institute for Chemical Biology;
   Scripps Translational Science Institute [UL1 RR025774]; National
   Institutes of Health [AG018917, U54 MH0845121]; NATIONAL CENTER FOR
   RESEARCH RESOURCES [UL1RR025774] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF MENTAL HEALTH [U54MH084512] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE ON AGING [R01AG018917] Funding Source: NIH RePORTER
FX The authors disclosed receipt of the following financial support for the
   research, authorship, and/or publication of this article: This work was
   supported by the Lita Annenberg Hazen Foundation, the Skaggs Institute
   for Chemical Biology, Grant UL1 RR025774 from the Scripps Translational
   Science Institute (J.W.K.), Grant AG018917 from the National Institutes
   of Health (J.W.K.), and Grant U54 MH0845121 from the National Institutes
   of Health (H.R.).
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NR 30
TC 19
Z9 20
U1 0
U2 12
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD JUL
PY 2013
VL 18
IS 6
BP 647
EP 658
DI 10.1177/1087057112469405
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Chemistry, Analytical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Chemistry
GA 170XI
UT WOS:000320888100002
PM 23230284
OA Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Chen, CL
   Liang, CM
   Chen, YH
   Tai, MC
   Lu, DW
   Chen, JT
AF Chen, Ching-Long
   Liang, Chang-Min
   Chen, Yi-Hao
   Tai, Ming-Cheng
   Lu, Da-Wen
   Chen, Jiann-Torng
TI Bevacizumab modulates epithelial-to-mesenchymal transition in the
   retinal pigment epithelial cells via connective tissue growth factor
   up-regulation
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE bevacizumab; connective tissue growth factor; Fc-Fc receptor; retinal
   pigment epithelial cells
ID PROLIFERATIVE DIABETIC-RETINOPATHY; COHERENCE TOMOGRAPHY FINDINGS;
   MACULAR DEGENERATION; INTRAVITREAL BEVACIZUMAB; CHOROIDAL
   NEOVASCULARIZATION; IN-VITRO; INJECTION; VITREORETINOPATHY; EXPRESSION;
   MEMBRANES
AB . Purpose: To investigate the effect of bevacizumab treatment on connective tissue growth factor (CTGF) expression and the induction of epithelial-to-mesenchymal transition in ARPE-19 cells and human donor retinal pigment epithelium (HRPE) cells in vitro. Methods: We quantitated the protein and gene expression level of CTGF by ELISA. The effect of FcFc receptor (FcFcR) interaction on CTGF expression was evaluated by CD64 siRNA silencing. Expression of epithelial-to-mesenchymal transition markers, alpha-smooth muscle actin (a-SMA) and zona occludens protein (ZO-1) was evaluated by Western blot. Cell migration and collagen gel contraction assay were examined by light microscopy, and collagen production was measured by ELISA. Results: Bevacizumab stimulation increased CTGF expression in ARPE-19 and HRPE cells in a dose-dependent manner. CD64 gene silencing inhibited the effect of bevacizumab-induced CTGF up-regulation. Bevacizumab increased the expression of a-SMA and decreased the expression of ZO-1 in ARPE-19 cells. Bevacizumab also caused the release of type-1 collagen and increased cell migration and contraction of collagen. Conclusions: Bevacizumab exerts pro-fibrotic effects on human RPE cells at clinical doses by up-regulation of CTGF expression via an FcFcR interaction. This effect of bevacizumab may be one of the underlying mechanisms involved in age-related macular degeneration therapy or intravitreal bevacizumab-associated complications.
C1 [Chen, Ching-Long; Liang, Chang-Min; Chen, Yi-Hao; Tai, Ming-Cheng; Lu, Da-Wen; Chen, Jiann-Torng] Triserv Gen Hosp, Dept Ophthalmol, Natl Def Med Ctr, Taipei 114, Taiwan.
   [Chen, Ching-Long; Liang, Chang-Min; Chen, Yi-Hao; Chen, Jiann-Torng] Natl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan.
   [Liang, Chang-Min] Natl Def Med Ctr, Grad Inst Aerosp & Undersea Med, Taipei, Taiwan.
C3 National Defense Medical Center; Tri-Service General Hospital; National
   Defense Medical Center; National Defense Medical Center
RP Chen, JT (通讯作者)，Triserv Gen Hosp, Dept Ophthalmol, Natl Def Med Ctr, 325 Cheng Kung Rd,Sect 2, Taipei 114, Taiwan.
EM jt66chen@ms32.hinet.net
FU Tri-Service General Hospital [TSGH-C99-087, TSGH-C101-099]; National
   Science Council [NSC 99-2314-B-016-009-MY3]
FX This work was supported in part by Grant TSGH-C99-087 and TSGH-C101-099
   from the Tri-Service General Hospital and by Grant NSC
   99-2314-B-016-009-MY3 from the National Science Council.
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NR 47
TC 21
Z9 22
U1 0
U2 2
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 AUG
PY 2012
VL 90
IS 5
BP e389
EP e398
DI 10.1111/j.1755-3768.2012.02426.x
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 980OV
UT WOS:000306903600009
PM 22712616
OA Bronze
DA 2022-11-30
ER

PT J
AU Roddy, GW
   Rosa, RH
   Oh, JY
   Ylostalo, JH
   Bartosh, TJ
   Choi, H
   Lee, RH
   Yasumura, D
   Ahern, K
   Nielsen, G
   Matthes, MT
   LaVail, MM
   Prockop, DJ
AF Roddy, Gavin W.
   Rosa, Robert H., Jr.
   Oh, Joo Youn
   Ylostalo, Joni H.
   Bartosh, Thomas J., Jr.
   Choi, Hosoon
   Lee, Ryang Hwa
   Yasumura, Douglas
   Ahern, Kelly
   Nielsen, Gregory
   Matthes, Michael T.
   LaVail, Matthew M.
   Prockop, Darwin J.
TI Stanniocalcin-1 Rescued Photoreceptor Degeneration in Two Rat Models of
   Inherited Retinal Degeneration
SO MOLECULAR THERAPY
LA English
DT Article
ID CILIARY NEUROTROPHIC FACTOR; CONE CELL-DEATH; RETINITIS-PIGMENTOSA;
   ANIMAL-MODELS; MACULAR DEGENERATION; TRANSGENIC RATS; SPATIAL VISION;
   STROMAL CELLS; RCS RAT; TRANSPLANTATION
AB Oxidative stress and photoreceptor apoptosis are prominent features of many forms of retinal degeneration (RD) for which there are currently no effective therapies. We previously observed that mesenchymal stem/stromal cells reduce apoptosis by being activated to secrete stanniocalcin-1 (STC-1), a multifunctional protein that reduces oxidative stress by upregulating mitochondrial uncoupling protein-2 (UCP-2). Therefore, we tested the hypothesis that intravitreal injection of STC-1 can rescue photoreceptors. We first tested STC-1 in the rhodopsin transgenic rat characterized by rapid photoreceptor loss. Intravitreal STC-1 decreased the loss of photoreceptor nuclei and transcripts and resulted in measurable retinal function when none is otherwise present in this rapid degeneration. We then tested STC-1 in the Royal College of Surgeons (RCS) rat characterized by a slower photoreceptor degeneration. Intravitreal STC-1 reduced the number of pyknotic nuclei in photoreceptors, delayed the loss of photoreceptor transcripts, and improved function of rod photoreceptors. Additionally, STC-1 upregulated UCP-2 and decreased levels of two protein adducts generated by reactive oxygen species (ROS). Microarrays from the two models demonstrated that STC-1 upregulated expression of a similar profile of genes for retinal development and function. The results suggested that intravitreal STC-1 is a promising therapy for various forms of RD including retinitis pigmentosa and atrophic age-related macular degeneration (AMD).
C1 [Roddy, Gavin W.; Oh, Joo Youn; Ylostalo, Joni H.; Bartosh, Thomas J., Jr.; Choi, Hosoon; Lee, Ryang Hwa; Prockop, Darwin J.] Texas A&M Hlth Sci Ctr, Inst Regenerat Med, Coll Med Scott & White, Temple, TX 76502 USA.
   [Rosa, Robert H., Jr.] Scott & White Eye Inst, Dept Ophthalmol, Temple, TX USA.
   [Yasumura, Douglas; Ahern, Kelly; Nielsen, Gregory; Matthes, Michael T.; LaVail, Matthew M.] UCSF Sch Med, Beckman Vis Ctr, San Francisco, CA USA.
C3 Texas A&M University System; Texas A&M University College Station; Texas
   A&M Health Science Center; University of California System; University
   of California San Francisco
RP Prockop, DJ (通讯作者)，Texas A&M Hlth Sci Ctr, Inst Regenerat Med, Coll Med Scott & White, 5701 Airport Rd, Temple, TX 76502 USA.
EM Prockop@medicine.tamhsc.edu
RI Ylostalo, Joni/AAH-9457-2019
OI Ylostalo, Joni/0000-0001-9746-1994
FU NIH [EY001919, EY006842, EY002162, PO1 RR 17447]; Scott & White Research
   Grants Program; Wynn-Gund TRAP and Research Center from the Foundation
   Fighting Blindness; Research to Prevent Blindness; NATIONAL CENTER FOR
   RESEARCH RESOURCES [P40RR017447] Funding Source: NIH RePORTER; NATIONAL
   EYE INSTITUTE [R01EY001919, F32EY006842, R37EY001919, R01EY006842,
   P30EY002162] Funding Source: NIH RePORTER
FX This study was supported by NIH grants EY001919, EY006842, EY002162, and
   PO1 RR 17447, Scott & White Research Grants Program, the Wynn-Gund TRAP
   and Research Center from the Foundation Fighting Blindness, and Research
   to Prevent Blindness. We gratefully acknowledge support from Laura
   Quinlivan for assistance with animal experiments. D.J.P. is a member of
   the scientific advisory board of Temple Therapeutics LLC. The other
   authors declared no conflict of interest.
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NR 50
TC 44
Z9 45
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD APR
PY 2012
VL 20
IS 4
BP 788
EP 797
DI 10.1038/mt.2011.308
PG 10
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 919XE
UT WOS:000302364700015
PM 22294148
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Li, YW
   Huang, DQ
   Xia, X
   Wang, ZY
   Luo, LY
   Wen, R
AF Li, Yiwen
   Huang, Deqiang
   Xia, Xin
   Wang, Zhengying
   Luo, Lingyu
   Wen, Rong
TI CCR3 and Choroidal Neovascularization
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; P70 S6 KINASE; MACULAR DEGENERATION;
   PHOSPHATIDYLINOSITOL 3-KINASE; IMMUNE-RESPONSE; RAPAMYCIN; RECEPTORS;
   DISEASE; VEGF; ANGIOGENESIS
AB Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly in industrialized countries. The "wet'' AMD, characterized by the development of choroidal neovacularization (CNV), could result in rapid and severe loss of central vision. The critical role of vascular endothelial growth factor A (VEGF-A) in CNV development has been established and VEGF-A neutralization has become the standard care for wet AMD. Recently, CCR3 was reported to play an important role in CNV development and that CCR3 targeting was reported to be superior to VEGF-A targeting in CNV suppression. We investigated the role of CCR3 in CNV development using the Matrigel induced CNV and found that in both rats and mice, CNV was well-developed in the control eyes as well as in eyes treated with CCR3 antagonist SB328437 or CCR3 neutralizing antibodies. No statistically significant difference in CNV areas was found between the control and SB328437 or CCR3-ab treated eyes. Immunostaining showed no specific expression of CCR3 in or near CNV. In contrast, both VEGF-A neutralizing antibodies and rapamycin significantly suppressed CNV. These results indicate that CCR3 plays no significant role in CNV development and question the therapeutic approach of CCR3 targeting to suppress CNV. On the other hand, our data support the therapeutic strategies of VEGF-A and mTOR (mammalian target of rapamycin) targeting for CNV.
C1 [Li, Yiwen; Huang, Deqiang; Xia, Xin; Wang, Zhengying; Luo, Lingyu; Wen, Rong] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Wen, Rong] Univ Miami, Miller Sch Med, Neurosci Program, Miami, FL 33136 USA.
C3 Bascom Palmer Eye Institute; University of Miami; University of Miami
RP Li, YW (通讯作者)，Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
EM rwen@med.miami.edu
FU National Institutes of Health [R01EY015289, R01EY018586, P30EY14801];
   Hope for Vision; State of Florida; Department of Defense
   [W81XWH-09-1-0674]; Research to Prevent Blindness; NATIONAL EYE
   INSTITUTE [R01EY018586, P30EY014801, R01EY015289] Funding Source: NIH
   RePORTER
FX This work was supported by grants from the National Institutes of Health
   (R01EY015289 and R01EY018586 to RW, and P30EY14801), Hope for Vision
   (RW), the James and Esther King Biomedical Research Program of the State
   of Florida (YL), and the Department of Defense (W81XWH-09-1-0674 to RW).
   It was also supported by an unrestricted grant from Research to Prevent
   Blindness to Bascom Palmer Eye Institute. 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 38
TC 30
Z9 33
U1 0
U2 10
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 FEB 15
PY 2011
VL 6
IS 2
AR e17106
DI 10.1371/journal.pone.0017106
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 721QH
UT WOS:000287369200022
PM 21358803
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Issa, PC
   Holz, FG
   Scholl, HPN
AF Issa, Peter Charbel
   Holz, Frank G.
   Scholl, Hendrik P. N.
TI Metamorphopsia in patients with macular telangiectasia type 2
SO DOCUMENTA OPHTHALMOLOGICA
LA English
DT Article
DE Macular telangiectasia; Metamorphopsia; Microperimetry; Amsler grid
ID JUXTAFOVEOLAR RETINAL TELANGIECTASIS; SCOTOMAS
AB Purpose To assess metamorphopsia in patients with macular telangiectasia (MacTel) type 2. Methods In a prospective observational cohort study, 40 eyes of 20 patients with MacTel type 2 were investigated by funduscopy, fluorescein angiography, optical coherence tomography and microperimetry. Metamorphopsia was assessed using Amsler grids following a standard protocol and standardized questionnaire. Results Metamorphopsia was present in 30 (83%) out of 36 nonproliferative eyes and in all four eyes with neovascular membranes. In the 30 nonproliferative eyes with distortions, metamorphopsia was always present in the nasal quadrant of the central visual field. Distortions were most pronounced in the nasal and lower quadrant in 70 and 30%, respectively. Three nonproliferative eyes with a very early and three eyes with a late disease stage did not perceive metamorphopsia. The degree of distortions was often but not necessarily correlated with the degree of leakage. Metamorphopsia was present in five out of eight eyes with normal sensitivity in microperimetry testing. Detection of scotoma by Amsler grid testing was poor. Conclusion Metamorphopsia is a frequent clinical symptom in MacTel type 2 even in the absence of neovascularization. Since macular thickness was within normal limits in such eyes, extensive swelling or distortion of the neurosensory retina would not account for metamorphopsia in contrast to other macular diseases such as age-related macular degeneration or idiopathic epiretinal membranes.
C1 [Issa, Peter Charbel; Holz, Frank G.; Scholl, Hendrik P. N.] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   [Issa, Peter Charbel] Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX2 6AW, England.
C3 University of Bonn; University of Oxford
RP Scholl, HPN (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM Hendrik.Scholl@ukb.uni-bonn.de
RI Issa, Peter Charbel/E-8935-2018; Issa, Peter Charbel/F-9603-2011; Issa,
   Peter Charbel/O-2580-2019
OI Issa, Peter Charbel/0000-0002-0351-6673; Issa, Peter
   Charbel/0000-0002-0351-6673
FU BONFOR [O-137.0011]; EU FP6, Integrated Project [LSHG-CT2005- 512036)]
FX Funding/Support BONFOR Program, grant O-137.0011 ( Faculty of Medicine,
   University of Bonn); Marie Curie Intra European Fellowship ( 237238)
   within the 7th European Community Framework Programme; The Lowy Medical
   Research Institute; The Macular Telangiectasia Project; EU FP6,
   Integrated Project "EVI-GENORET'' (LSHG-CT2005- 512036). Financial
   Disclosure No conflicting relationship exists for any author.
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NR 21
TC 34
Z9 33
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0012-4486
EI 1573-2622
J9 DOC OPHTHALMOL
JI Doc. Ophthalmol.
PD OCT
PY 2009
VL 119
IS 2
BP 133
EP 140
DI 10.1007/s10633-009-9190-9
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 498UM
UT WOS:000270169600006
PM 19711108
DA 2022-11-30
ER

PT J
AU Wu, ZH
   Lauer, TW
   Sick, A
   Hackett, SF
   Campochiaro, PA
AF Wu, Zhihao
   Lauer, Thomas W.
   Sick, Anna
   Hackett, Sean F.
   Campochiaro, Peter A.
TI Oxidative stress modulates complement factor H expression in retinal
   Pigmented epithelial cells by acetylation of FOXO3
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FORKHEAD TRANSCRIPTION FACTORS; GLOMERULONEPHRITIS TYPE-II; MACULAR
   DEGENERATION; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; DEPOSIT DISEASE;
   PROTEIN; KINASE; RISK; POLYMORPHISM; SURVIVAL
AB Age-related macular degeneration (AMD), the leading cause of severe vision loss in the elderly, is a complex disease that results from genetic modifications that increase susceptibility to environmental exposures. Smoking, a major source of oxidative stress, increases the incidence and severity of AMD, and antioxidants slow progression, suggesting that oxidative stress plays a major role. Polymorphisms in the complement factor H (CFH) gene that reduce activity of CFH increase the risk of AMD. In this study we demonstrate an interaction between these two risk factors, because oxidative stress reduces the ability of an inflammatory cytokine, interferon-gamma, to increase CFH expression in retinal pigmented epithelial cells. The interferon-gamma-induced increase in CFH is mediated by transcriptional activation by STAT1, and its suppression by oxidative stress is mediated by acetylation of FOXO3, which enhances FOXO3 binding to the CFH promoter, reduces its binding to STAT1, inhibits STAT1 interaction with the CFH promoter, and reduces expression of CFH. Expression of SIRT1, a mammalian homolog of NAD-dependent protein deacetylase sir2, attenuated FOXO3 recruitment to the CFH regulatory region and reversed the H2O2-induced repression of CFH gene expression. These data suggest an important interaction between environmental exposure and genetic susceptibility in the pathogenesis of AMD and, by elucidating molecular signaling involved in the interaction, provide potential targets for therapeutic intervention.
C1 Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA.
   Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins University
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Maumenee 719,600 N Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhmi.edu
OI Sick-Samuels, Anna/0000-0002-9247-9340
FU NEI NIH HHS [P30EY0572, P30EY1765, EY05951] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [P30EY001765] Funding Source: NIH RePORTER
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NR 48
TC 90
Z9 94
U1 0
U2 7
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 AUG 3
PY 2007
VL 282
IS 31
BP 22414
EP 22425
DI 10.1074/jbc.M702321200
PG 12
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 194OR
UT WOS:000248354200020
PM 17558024
OA hybrid
DA 2022-11-30
ER

PT J
AU Tisi, A
   Pulcini, F
   Carozza, G
   Mattei, V
   Flati, V
   Passacantando, M
   Antognelli, C
   Maccarone, R
   Delle Monache, S
AF Tisi, Annamaria
   Pulcini, Fanny
   Carozza, Giulia
   Mattei, Vincenzo
   Flati, Vincenzo
   Passacantando, Maurizio
   Antognelli, Cinzia
   Maccarone, Rita
   Delle Monache, Simona
TI Antioxidant Properties of Cerium Oxide Nanoparticles Prevent Retinal
   Neovascular Alterations In Vitro and In Vivo
SO ANTIOXIDANTS
LA English
DT Article
DE oxidative stress; wet AMD; VEGF; RPE; cerium oxide nanoparticles;
   ARPE-19; HUVEC; angiogenesis; glycative stress
ID NF-KAPPA-B; HYDROGEN-PEROXIDE; ENDOTHELIAL-CELLS; OXIDATIVE STRESS;
   MECHANISMS; ANGIOGENESIS; INDUCTION; APOPTOSIS; DESENSITIZATION;
   INVOLVEMENT
AB In this study, we investigated whether cerium oxide nanoparticles (CeO2-NPs), a promising antioxidant nanomaterial, may contrast retinal vascular alterations induced by oxidative damage in vitro and in vivo. For the in vivo experiments, the light damage (LD) animal model of Age-Related Macular Degeneration (AMD) was used and the CeO2-NPs were intravitreally injected. CeO2-NPs significantly decreased vascular endothelial growth factor (VEGF) protein levels, reduced neovascularization in the deep retinal plexus, and inhibited choroidal sprouting into the photoreceptor layer. The in vitro experiments were performed on human retinal pigment epithelial (ARPE-19) cells challenged with H2O2; we demonstrated that CeO2-NPs reverted H2O2-induced oxidative stress-dependent effects on this cell model. We further investigated the RPE-endothelial cells interaction under oxidative stress conditions in the presence or absence of CeO2-NPs through two experimental paradigms: (i) treatment of human umbilical vein endothelial cells (HUVECs) with conditioned media from ARPE-19 cells, and (ii) coculture of ARPE-19 and HUVECs. In both experimental conditions, CeO2-NPs were able to revert the detrimental effect of H2O2 on angiogenesis in vitro by realigning the level of tubule formation to that of the control. Altogether, our results indicate, for the first time, that CeO2-NPs can counteract retinal neovascularization and may be a new therapeutic strategy for the treatment of wet AMD.
C1 [Tisi, Annamaria; Pulcini, Fanny; Carozza, Giulia; Flati, Vincenzo; Maccarone, Rita; Delle Monache, Simona] Univ Aquila, Dept Biotechnol & Appl Clin Sci, I-67100 Laquila, Italy.
   [Mattei, Vincenzo] Sabina Univ, Biomed & Adv Technol Rieti Ctr, I-02100 Rieti, Italy.
   [Passacantando, Maurizio] Univ Aquila, Dept Phys & Chem Sci, I-67100 Laquila, Italy.
   [Antognelli, Cinzia] Univ Perugia, Dept Med & Surg, Biosci & Med Embryol Div, I-06129 Perugia, Italy.
C3 University of L'Aquila; University of L'Aquila; University of Perugia
RP Maccarone, R; Delle Monache, S (通讯作者)，Univ Aquila, Dept Biotechnol & Appl Clin Sci, I-67100 Laquila, Italy.; Antognelli, C (通讯作者)，Univ Perugia, Dept Med & Surg, Biosci & Med Embryol Div, I-06129 Perugia, Italy.
EM annamaria.tisi@univaq.it; fanny.pulcini@graduate.univaq.it;
   giulia.carozza@graduate.univaq.it; v.mattei@sabinauniversitas.it;
   vincenzo.flati@univaq.it; maurizio.passacantando@univaq.it;
   cinzia.antognelli@unipg.it; rita.maccarone@univaq.it;
   simona.dellemonache@univaq.it
RI Delle Monache, Simona/M-5618-2014; Mattei, Vincenzo/AAQ-3667-2020;
   PASSACANTANDO, Maurizio/A-2122-2019; FLATI, VINCENZO/R-6231-2018
OI Delle Monache, Simona/0000-0002-8153-915X; Mattei,
   Vincenzo/0000-0003-4677-088X; ANTOGNELLI, Cinzia/0000-0002-8259-680X;
   Carozza, Giulia/0000-0002-2130-3444; MACCARONE,
   Rita/0000-0003-0648-3771; PASSACANTANDO, Maurizio/0000-0002-3680-5295;
   FLATI, VINCENZO/0000-0003-1014-297X
FU intramural "DISCAB grant 2021" (Department of Biotechnological and
   Applied Clinical Sciences)
FX This work was supported by the intramural "DISCAB grant 2021" (conferred
   by the Department of Biotechnological and Applied Clinical Sciences) for
   R.M. and S.D.M.
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NR 59
TC 1
Z9 1
U1 3
U2 3
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD JUN
PY 2022
VL 11
IS 6
AR 1133
DI 10.3390/antiox11061133
PG 22
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 2K1LO
UT WOS:000816105500001
PM 35740031
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Chen, QQ
   Tang, L
   Zhang, Y
   Wan, CY
   Yu, XX
   Dong, YM
   Chen, XT
   Wang, XL
   Li, N
   Xin, G
   Zhang, MX
   Chen, Z
   Niu, H
   Huang, W
AF Chen, Qingqiu
   Tang, Li
   Zhang, Yi
   Wan, Chengyu
   Yu, Xiuxian
   Dong, Yuman
   Chen, Xiaoting
   Wang, Xueling
   Li, Ning
   Xin, Guang
   Zhang, Meixia
   Chen, Zhen
   Niu, Hai
   Huang, Wen
TI STING up-regulates VEGF expression in oxidative stress-induced
   senescence of retinal pigment epithelium via NF-kappa B/HIF-1 alpha
   pathway
SO LIFE SCIENCES
LA English
DT Article
DE VEGF; STING; Senescence; Autophagic flux; Retinal pigment epithelium
ID INDUCED PREMATURE SENESCENCE; DNA-DAMAGE; CELLS-IMPLICATIONS; AUTOPHAGY;
   RPE; DEGENERATION; INFLAMMATION; ACTIVATION; DISEASE
AB Aim: Aging-related dysfunction of retinal pigment epithelium (RPE) is the main pathogenic factors for pathological angiogenesis due to dysregulated vascular endothelial growth factor (VEGF) in retinal vascular diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). However, the molecular mechanism behind the up-regulation of VEGF in senescent RPE is still blurred.
   Materials and methods: As oxidative damage is the key cause of RPE dysfunction, we employed a model of oxidative stress-induced premature senescence of ARPE-19 to explore the effect of senescent RPE on VEGF.
   Key findings: We reported that senescent ARPE-19 up-regulated VEGF expression under both short-term and prolonged H2O2 treatment, accompanying with increased HIF-1 alpha, the key mediator of VEGF. STING signaling, which could be activated by oxidative stress-damaged DNA, was also observed to be increased in senescent ARPE-19 treated with H2O2. And the inhibition of STING significantly reduced HIF-1 alpha expression to alleviate the up-regulation of VEGF. NF-kappa B was also shown to be involved in the regulation of VEGF in senescent ARPE-19 in response to STING signaling. Furthermore, oxidative stress impaired the lysosomal clearance of damaged DNA to enhance STING signaling, thereby up-regulating VEGF expression in senescent RPE.
   Significance: Our data provide evidence that STING plays an important role in VEGF regulation in senescent RPE induced by oxidative stress.
C1 [Chen, Qingqiu; Wan, Chengyu; Yu, Xiuxian; Dong, Yuman; Xin, Guang; Chen, Zhen; Niu, Hai; Huang, Wen] Sichuan Univ, Tissue Orientated Property Chinese Med Key Lab Si, West China Sch Med, Lab Ethnopharmacol,West China Hosp, Chengdu, Sichuan, Peoples R China.
   [Tang, Li] Sichuan Univ, West China Hosp, Dept Ophthalmol, Chengdu, Sichuan, Peoples R China.
   [Zhang, Yi] Sichuan Univ, West China Hosp, Res Core Facil, Chengdu, Sichuan, Peoples R China.
   [Chen, Xiaoting] Sichuan Univ, West China Hosp, Anim Expt Ctr, Chengdu, Sichuan, Peoples R China.
   [Wang, Xueling; Li, Ning] Sichuan Univ, West China Hosp, Integrated Chinese & Western Med Dept, Chengdu, Sichuan, Peoples R China.
   [Zhang, Meixia] Sichuan Univ, West China Hosp, Dept Ophthalmol, Macular Dis Res Lab, Chengdu, Sichuan, Peoples R China.
C3 Sichuan University; Sichuan University; Sichuan University; Sichuan
   University; Sichuan University; Sichuan University
RP Huang, W (通讯作者)，Keyuan Rd 4 1,Gaopeng Ave, 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, 81803966];
   National Major Scientific and Technological Special Project for
   'Significant New Drugs Development' [2019ZX09201005-005-001,
   2019ZX09201005-005-004]; Innovative Chinese Medicine and Health Products
   Research Academician Workstation of Academician Boli Zhang and
   Academician Beiwei Zhu, West China Hospital, Sichuan University
   [HXYS19001, HXYS19002]; Post-Doctor Research Project, West China
   Hospital, Sichuan University [2019HXBH024]; China Postdoctoral Science
   Foundation [2019M663533]
FX This study was supported by the National Natural Science Foundation of
   China (Grant No. 81973580, 81803966), the National Major Scientific and
   Technological Special Project for 'Significant New Drugs Development'
   (Grant No. 2019ZX09201005-005-001, and 2019ZX09201005-005-004),
   Innovative Chinese Medicine and Health Products Research Academician
   Workstation of Academician Boli Zhang and Academician Beiwei Zhu, West
   China Hospital, Sichuan University (Grant No. HXYS19001, HXYS19002),
   Post-Doctor Research Project, West China Hospital, Sichuan University
   (Grant No. 2019HXBH024), the Project funded by China Postdoctoral
   Science Foundation (Grant no. 2019M663533). We thank Bing Zhou for using
   ChemiDoc T -XRS imaging system.
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NR 43
TC 1
Z9 1
U1 1
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0024-3205
EI 1879-0631
J9 LIFE SCI
JI Life Sci.
PD MAR 15
PY 2022
VL 293
AR 120089
DI 10.1016/j.lfs.2021.120089
PG 11
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 0G1GV
UT WOS:000777802100005
PM 35007563
DA 2022-11-30
ER

PT J
AU Mulfaul, K
   Mullin, NK
   Giacalone, JC
   Voigt, AP
   DeVore, M
   Stone, EM
   Tucker, BA
   Mullins, RF
AF Mulfaul, Kelly
   Mullin, Nathaniel K.
   Giacalone, Joseph C.
   Voigt, Andrew P.
   DeVore, Melette
   Stone, Edwin M.
   Tucker, Budd A.
   Mullins, Robert F.
TI Local factor H production by human choroidal endothelial cells mitigates
   complement deposition: implications for macular degeneration
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE age-related macular degeneration; FH; choroidal endothelial cells;
   membrane attack complex (MAC)
ID PIGMENT EPITHELIAL-CELLS; MEMBRANE ATTACK COMPLEX; BRUCHS MEMBRANE;
   ALTERNATIVE PATHWAY; HUMAN EYES; DISEASE; COMMON; PROTEINS; BINDING;
   RISK
AB Activation of the alternative complement pathway is an initiating event in the pathology of age-related macular degeneration (AMD). Unchecked complement activation leads to the formation of a pro-lytic pore, the membrane attack complex (MAC). MAC deposition is observed on the choriocapillaris of AMD patients and likely causes lysis of choroidal endothelial cells (CECs). Complement factor H (FH, encoded by the gene CFH) is an inhibitor of complement. Both loss of function of FH and reduced choroidal levels of FH have been reported in AMD. It is plausible that reduced local FH availability promotes MAC deposition on CECs. FH is produced primarily in the liver; however, cells including the retinal pigment epithelium can produce FH locally. We hypothesized that CECs produce FH locally to protect against MAC deposition. We aimed to investigate the effect of reduced FH levels in the choroid to determine whether increasing local FH could protect CECs from MAC deposition. We demonstrated that siRNA knockdown of FH (CFH) in human immortalized CECs results in increased MAC deposition. We generated AMD iPSC-derived CECs and found that overexpression of FH protects against MAC deposition. These results suggest that local CEC-produced FH protects against MAC deposition, and that increasing local FH protein may be beneficial in limiting MAC deposition in AMD. (c) 2022 The Pathological Society of Great Britain and Ireland.
C1 [Mulfaul, Kelly; Mullin, Nathaniel K.; Giacalone, Joseph C.; Voigt, Andrew P.; DeVore, Melette; Stone, Edwin M.; Tucker, Budd A.; Mullins, Robert F.] Univ Iowa, Inst Vis Res, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
C3 University of Iowa
RP Mullins, RF (通讯作者)，Inst Vis Res, 375 Newton Rd, Iowa City, IA 52242 USA.
EM robert-mullins@uiowa.edu
OI Mulfaul, Kelly/0000-0003-4441-4806; Mullin,
   Nathaniel/0000-0003-4320-2852; Voigt, Andrew/0000-0001-8107-8317; Stone,
   Edwin M./0000-0003-3343-4414; Tucker, Budd/0000-0003-2178-1742
FU National Institutes of Health [EY-024605, EY-025580]; Elmer & Sylvia
   Sramek Charitable Trust; Fight for Sight [PD-20005]; Edward N. & Della
   L. Thome Memorial Foundation
FX This research was funded by the National Institutes of Health grants
   EY-024605 and EY-025580, the Elmer & Sylvia Sramek Charitable Trust,
   Fight for Sight PD-20005, and The Edward N. & Della L. Thome Memorial
   Foundation.
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NR 55
TC 5
Z9 5
U1 0
U2 4
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 MAY
PY 2022
VL 257
IS 1
BP 29
EP 38
DI 10.1002/path.5867
EA FEB 2022
PG 10
WC Oncology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Pathology
GA 0K6RD
UT WOS:000756612800001
PM 35038170
DA 2022-11-30
ER

PT J
AU Fontaine, V
   Fournie, M
   Monteiro, E
   Boumedine, T
   Balducci, C
   Guibout, L
   Latil, M
   Sahel, JA
   Veillet, S
   Dilda, PJ
   Lafont, R
   Camelo, S
AF Fontaine, Valerie
   Fournie, Mylene
   Monteiro, Elodie
   Boumedine, Thinhinane
   Balducci, Christine
   Guibout, Louis
   Latil, Mathilde
   Sahel, Jose-Alain
   Veillet, Stanislas
   Dilda, Pierre J.
   Lafont, Rene
   Camelo, Serge
TI A2E-induced inflammation and angiogenesis in RPE cells in vitro are
   modulated by PPAR-alpha, -beta/delta, -gamma, and RXR antagonists and by
   norbixin
SO AGING-US
LA English
DT Article
DE retinylethanolamine (A2E); norbixin; peroxisome proliferator-activated
   receptor (PPAR); retinal pigment epithelium (RPE); retinoic X receptor
   (RXR)
ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; MACULAR
   DEGENERATION; BETA-CAROTENE; X-RECEPTOR; AGE; LIPOFUSCIN; A2E;
   ACTIVATION; LIVER
AB N-retinylidene-N-retinylethanolamine (A2E) plays a central role in age-related macular degeneration (AMD) by inducing angiogenesis and inflammation. A2E effects are mediated at least partly via the retinoic acid receptor (RAR)-a. Here we show that A2E binds and transactivates also peroxisome proliferator-activated receptors (PPAR) and retinoid X receptors (RXR). 9'-cis-norbixin, a di-apocarotenoid is also a ligand of these nuclear receptors (NR). Norbixin inhibits PPAR and RXR transactivation induced by A2E. Moreover, norbixin reduces protein kinase B (AKT) phosphorylation, NF-kappa B and AP-1 transactivation and mRNA expression of the inflammatory interleukins (IL) -6 and -8 and of vascular endothelial growth factor (VEGF) enhanced by A2E. By contrast, norbixin increases matrix metalloproteinase 9 (MMP9) and C-C motif chemokine ligand 2 (CCL2) mRNA expression in response to A2E. Selective PPAR-alpha, -beta/delta and -gamma antagonists inhibit the expression of IL-6 and IL-8 while only the antagonist of PPAR-. inhibits the transactivation of NF-kappa B following A2E exposure. In addition, a cocktail of all three PPARs antagonists and also HX531, an antagonist of RXR reproduce norbixin effects on inflammation. Altogether, A2E's deleterious biological effects could be inhibited through PPAR and RXR regulation. Moreover, the modulation of these NR by norbixin may open new avenues for the treatment of AMD.
C1 [Fontaine, Valerie; Fournie, Mylene; Monteiro, Elodie; Sahel, Jose-Alain] Sorbonne Univ, CNRS, INSERM, Inst Vis, F-75012 Paris, France.
   [Balducci, Christine; Guibout, Louis; Latil, Mathilde; Sahel, Jose-Alain; Veillet, Stanislas; Dilda, Pierre J.; Lafont, Rene; Camelo, Serge] Sorbonne Univ, Biophytis, F-75005 Paris, France.
   [Sahel, Jose-Alain] Fondat Ophtalmolog Rothschild, F-75019 Paris, France.
   [Sahel, Jose-Alain] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15213 USA.
C3 Centre National de la Recherche Scientifique (CNRS); Institut National
   de la Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite; Universite Paris Cite; UDICE-French
   Research Universities; Sorbonne Universite; Pennsylvania Commonwealth
   System of Higher Education (PCSHE); University of Pittsburgh
RP Fontaine, V (通讯作者)，Sorbonne Univ, CNRS, INSERM, Inst Vis, F-75012 Paris, France.
EM valerie.fontaine@inserm.fr
RI LAFONT, Rene/GYA-4891-2022
FU Biophytis; Programme Investissements d'Avenir IHU FOReSIGHT
   [ANR-18-IAHU-01]
FX This work was supported by Biophytis and completed with the support of
   the Programme Investissements d'Avenir IHU FOReSIGHT (ANR-18-IAHU-01).
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NR 54
TC 6
Z9 6
U1 0
U2 2
PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD SEP 30
PY 2021
VL 13
IS 18
BP 22040
EP 22058
PG 19
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA WC5JD
UT WOS:000704292100015
PM 34544906
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Hikichi, T
AF Hikichi, Taiichi
TI Three Japanese cases of intraocular inflammation after intravitreal
   brolucizumab injections in one clinic
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Anti-vascular endothelial growth factor therapy; Intraocular
   inflammation; Neovascular age-related macular degeneration; Steroid
AB Introduction To report the development of intraocular inflammation (IOI) in three Japanese patients in the same clinic after intravitreal injections (IVI) of brolucizumab to treat neovascular age-related macular degeneration. Cases reports The major findings were: (1) all three eyes had a history of treatment with multiple anti-vascular endothelial growth factor (VEGF) agents; (2) the time to the onset of IOI after the first IVI of brolucizumab varied, i.e., onset occurred after the first IVI in two cases and after the second IVI in one case; (3) the degree of vitreous opacities resulting from the IOI varied among the three cases and directly affected the degree of the decrease in the visual acuity (VA) and the timing of the VA recovery; (4) an injection of triamcinolone acetonide into the sub-Tenon's capsule (STTA) resulted in resolution of the IOI and improvement of the VA; and (5) the sheathed retinal vessels indicating vasculitis improved associated with reduction of the IOI after STTA. Comments Although all three cases responded well to the injection of triamcinolone acetonide into the sub-Tenon's capsule, physicians should fully disclose to patients both the potential for this adverse effect, especially those patients with a history of anti-VEGF therapy, and the benefits of therapy with brolucizumab. Immediate steroid therapy is recommended to possibly reduce deterioration of the visual function caused by persistent IOI.
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 American Society of Retina Specialists, 2020, BEOVU UPDATE ASRS ME
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NR 16
TC 7
Z9 7
U1 0
U2 0
PU SPRINGER JAPAN KK
PI TOKYO
PA SHIROYAMA TRUST TOWER 5F, 4-3-1 TORANOMON, MINATO-KU, TOKYO, 105-6005,
   JAPAN
SN 0021-5155
EI 1613-2246
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD MAR
PY 2021
VL 65
IS 2
BP 208
EP 214
DI 10.1007/s10384-021-00819-7
EA FEB 2021
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QZ0AH
UT WOS:000614709300001
PM 33543351
DA 2022-11-30
ER

PT J
AU Perez-Ortiz, AC
   Peralta-Ildefonso, MJ
   Lira-Romero, E
   Moya-Albor, E
   Brieva, J
   Ramirez-Sanchez, I
   Clapp, C
   Luna-Angulo, A
   Rendon, A
   Adan-Castro, E
   Ramirez-Hernandez, G
   Diaz-Lezama, N
   Coral-Vazquez, RM
   Estrada-Mena, FJ
AF Perez-Ortiz, Andric C.
   Peralta-Ildefonso, Martha J.
   Lira-Romero, Esmeralda
   Moya-Albor, Ernesto
   Brieva, Jorge
   Ramirez-Sanchez, Israel
   Clapp, Carmen
   Luna-Angulo, Alexandra
   Rendon, Alvaro
   Adan-Castro, Elva
   Ramirez-Hernandez, Gabriela
   Diaz-Lezama, Nundehui
   Coral-Vazquez, Ramon M.
   Estrada-Mena, Francisco J.
TI Lack of Delta-Sarcoglycan (Sgcd) Results in Retinal Degeneration
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE dystrophin-associated protein complex; delta-sarcoglycan; knock-out
   mice; age-related macular degeneration; geographic atrophy; retinal
   degeneration
ID MACULAR DEGENERATION; GLOBAL PREVALENCE; VISION IMPAIRMENT; DYSTROPHIN;
   SUSCEPTIBILITY; COMPLEX; ASSOCIATION; ALPHA
AB Age-related macular degeneration (AMD) is the leading cause of central vision loss and severe blindness among the elderly population. Recently, we reported on the association of the SGCD gene (encoding for delta -sarcoglycan) polymorphisms with AMD. However, the functional consequence of Sgcd alterations in retinal degeneration is not known. Herein, we characterized changes in the retina of the Sgcd knocked-out mouse (KO, Sgcd(-/-)). At baseline, we analyzed the retina structure of three-month-old wild-type (WT, Sgcd(+/+)) and Sgcd(-/-) mice by hematoxylin and eosin (H&E) staining, assessed the Sgcd-protein complex (alpha-, beta-, gamma-, and epsilon -sarcoglycan, and sarcospan) by immunofluorescence (IF) and Western blot (WB), and performed electroretinography. Compared to the WT, Sgcd(-/-) mice are five times more likely to have retinal ruptures. Additionally, all the retinal layers are significantly thinner, more so in the inner plexiform layer (IPL). In addition, the number of nuclei in the KO versus the WT is ever so slightly increased. WT mice express Sgcd-protein partners in specific retinal layers, and as expected, KO mice have decreased or no protein expression, with a significant increase in the alpha subunit. At three months of age, there were no significant differences in the scotopic electroretinographic responses, regarding both a- and b-waves. According to our data, Sgcd(-/-) has a phenotype that is compatible with retinal degeneration.
C1 [Perez-Ortiz, Andric C.] Massachusetts Gen Hosp, Div Surg, 55 Fruit St, Boston, MA 02214 USA.
   [Perez-Ortiz, Andric C.] Yale Univ, Sch Publ Hlth, Lab Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06510 USA.
   [Peralta-Ildefonso, Martha J.] Univ Nacl Autonoma Mexico, Fac Quim, Mexico City 04510, DF, Mexico.
   [Peralta-Ildefonso, Martha J.; Lira-Romero, Esmeralda] Univ Panamer, Escuela Med, Lab Biol Mol, Donatello 59 Insurgentes Mixcoac Benito Juarez, Mexico City 03920, DF, Mexico.
   [Moya-Albor, Ernesto; Brieva, Jorge; Estrada-Mena, Francisco J.] Univ Panamer, Fac Ingn, Augusto Rodin 498, Mexico City 03920, DF, Mexico.
   [Ramirez-Sanchez, Israel; Coral-Vazquez, Ramon M.] Inst Politecn Nacl, Escuela Super Med, Secc Estudios Posgrad & Invest, Mexico City 11340, DF, Mexico.
   [Clapp, Carmen; Adan-Castro, Elva; Ramirez-Hernandez, Gabriela] UNAM, Inst Neurobiol, Campus UNAM Juriquilla, Queretaro 76230, Mexico.
   [Luna-Angulo, Alexandra] Inst Nacl Rehabil, Dept Neurociencias, 289 Arenal Guadalupe, Mexico City 14389, DF, Mexico.
   [Rendon, Alvaro] Sorbonne Univ, Inst Vis, F-75012 Paris, France.
   [Diaz-Lezama, Nundehui] Ludwig Maximilians Univ Munchen, Dept Physiol Genom, Grosshaderner Str 9, D-82152 Planegg Martinsried, Germany.
   [Coral-Vazquez, Ramon M.] Ctr Med Nacl 20 Noviembre, Inst Seguridad & Serv Sociales Trabajadores Estad, Subdirecc Ensenanza & Invest, Mexico City 03100, DF, Mexico.
C3 Harvard University; Massachusetts General Hospital; Yale University;
   Universidad Nacional Autonoma de Mexico; Universidad Panamericana -
   Ciudad de Mexico; Universidad Panamericana - Ciudad de Mexico; Instituto
   Politecnico Nacional - Mexico; Universidad Nacional Autonoma de Mexico;
   UDICE-French Research Universities; Sorbonne Universite; University of
   Munich
RP Estrada-Mena, FJ (通讯作者)，Univ Panamer, Fac Ingn, Augusto Rodin 498, Mexico City 03920, DF, Mexico.; Coral-Vazquez, RM (通讯作者)，Inst Politecn Nacl, Escuela Super Med, Secc Estudios Posgrad & Invest, Mexico City 11340, DF, Mexico.; Coral-Vazquez, RM (通讯作者)，Ctr Med Nacl 20 Noviembre, Inst Seguridad & Serv Sociales Trabajadores Estad, Subdirecc Ensenanza & Invest, Mexico City 03100, DF, Mexico.
EM andric@aya.yale.edu; martha.janneth2830@gmail.com; elira@up.edu.mx;
   emoya@up.edu.mx; jbrieva@up.edu.mx; iramirez@up.edu.mx; clapp@unam.mx;
   lunangulo@gmail.com; alvaro.rendon@inserm.fr; elva.adan@gmail.com;
   gaby.farmafesc@gmail.com; nundehuidiaz@gmail.com; rmcoralv@gmail.com;
   festrada@up.edu.mx
RI Perez-Ortiz, Andric C/AAA-3292-2019; Estrada-Mena,
   Francisco/AAI-2437-2020; luna, alexandra/AAA-5836-2021; Moya-Albor,
   Ernesto/J-1891-2019
OI Perez-Ortiz, Andric C/0000-0003-0731-2464; Estrada-Mena,
   Francisco/0000-0002-0833-3630; Moya-Albor, Ernesto/0000-0002-9637-786X;
   Lira, Esmeralda/0000-0002-9838-1731
FU Universidad Panamericana through the grant "Fomento a la Investigacion
   UP [UP-CI-2017-CS-MX-01]; CONACyT [28398]
FX This research was funded by Universidad Panamericana through the grant
   "Fomento a la Investigacion UP 2017", grant number UP-CI-2017-CS-MX-01
   and partially funded by CONACyT (Grant number: 28398) to Israel
   Ramirez-Sanchez.
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NR 33
TC 4
Z9 4
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 NOV
PY 2019
VL 20
IS 21
AR 5480
DI 10.3390/ijms20215480
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA JQ4VU
UT WOS:000498946100238
PM 31689918
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Nielsen, MK
   Subhi, Y
   Molbech, CR
   Nilsson, LL
   Nissen, MH
   Sorensen, TL
AF Nielsen, Marie Krogh
   Subhi, Yousif
   Molbech, Christopher Rue
   Nilsson, Line Lynge
   Nissen, Mogens Holst
   Sorensen, Torben Lykke
TI Imbalances in tissue inhibitors of metalloproteinases differentiate
   choroidal neovascularization from geographic atrophy
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization;
   geographic atrophy; matrix metalloproteinases; tissue inhibitors of
   metalloproteinases
ID RETINAL-PIGMENT EPITHELIUM; CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN;
   BRUCHS MEMBRANE; MATRIX METALLOPROTEINASES; MACULAR DEGENERATION;
   MORPHOMETRIC-ANALYSIS; ALZHEIMERS-DISEASE; PLASMA-LEVELS;
   MATRIX-METALLOPROTEINASE-9
AB Purpose Tissue inhibitor of metalloproteinase (TIMP) is known to play a role in age-related macular degeneration (AMD). We wished to investigate alterations in different late stages of AMD: neovascular AMD and geographic atrophy (GA). Methods This was a prospective case-control study. A total of 125 participants were included consecutively during a period of 18 months. We included 46 patients with neovascular AMD, 46 patients with GA without any sign of choroidal neovascularization in either eye, and 33 healthy aged controls. Patients with immune-affecting disorders were not included. Commercial immunoassay kits were used to quantify levels of TIMP-1, TIMP-3, MMP-2 and MMP-9 in blood plasma. Results We found that patients with neovascular AMD had lower plasma concentration of TIMP-3 (p = 0.028) than healthy controls. Patients with GA had higher plasma levels of TIMP-1 (p < 0.001) and MMP-9 (p = 0.022) compared to healthy controls. Also, we found that TIMP-1 levels in patients with GA increased with age (Spearman's rho = 0.04, p = 0.006). Conclusion Matrix metalloproteinases (MMPs) and TIMPs, which are known to be involved in age-related changes in Bruch's membrane, are significantly altered systemically, suggesting the presence of an imbalance in the homeostasis of the extracellular matrix. These imbalances may explain differences in the clinical manifestation of late AMD.
C1 [Nielsen, Marie Krogh; Subhi, Yousif; Molbech, Christopher Rue; Sorensen, Torben Lykke] Zealand Univ Hosp, Dept Ophthalmol, Clin Eye Res Div, Vestermarksvej 23, DK-4000 Roskilde, Denmark.
   [Nielsen, Marie Krogh; Subhi, Yousif; Molbech, Christopher Rue; Nilsson, Line Lynge; Sorensen, Torben Lykke] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
   [Nilsson, Line Lynge] Zealand Univ Hosp, CIRRI, Dept Clin Biochem, Roskilde, Denmark.
   [Nissen, Mogens Holst] Univ Copenhagen, Dept Immunol & Microbiol, Eye Res Unit, Copenhagen, Denmark.
C3 University of Copenhagen; University of Copenhagen
RP Nielsen, MK (通讯作者)，Zealand Univ Hosp, Dept Ophthalmol, Clin Eye Res Div, Vestermarksvej 23, DK-4000 Roskilde, Denmark.
EM mrrm@regionsjaelland.dk
RI Subhi, Yousif/ABG-6330-2020
OI Subhi, Yousif/0000-0001-6620-5365; Krogh Nielsen,
   Marie/0000-0003-3804-7296
FU Velux Foundation; Fight for Sight Denmark; Region Zealand;
   Synoptik-Fonden
FX This research was funded by grants from the Velux Foundation, Fight for
   Sight Denmark, the Region Zealand, and Synoptik-Fonden.
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NR 52
TC 16
Z9 16
U1 0
U2 2
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 FEB
PY 2019
VL 97
IS 1
BP 84
EP 90
DI 10.1111/aos.13894
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HJ0SF
UT WOS:000456872000023
PM 30288950
OA Bronze
DA 2022-11-30
ER

PT J
AU Lin, W
   Xu, GX
AF Lin, Wen
   Xu, Guoxing
TI Over-expression of CNTF in bone marrow mesenchymal stem cells protects
   RPE cells from short-wavelength, blue-light injury
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Article
DE Blue-light (BL); Retinal pigment epithelium (RPE); Bone marrow
   mesenchymal stem cells (BMSCs); Ciliary neurotrophic factor (CNTF)
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; OXIDATIVE STRESS; RAT
   MODEL; AUTOPHAGY; DAMAGE; DEATH; TRANSPLANTATION; NEUROTROPHINS;
   CONSEQUENCES
AB Increasing evidence has demonstrated that excessive blue-light (BL) with high photochemical energy and phototoxicity could induce apoptosis in retinal pigment epithelium (RPE) cells. RPE apoptosis leads to retina damage and further aggravate age-related macular degeneration (ARMD). Because of their neuroprotective, plasticity, and immunomodulatory ability, bone marrow mesenchymal stem cells (BMSCs) are recognized for retinal neuroprotection. RPE cells possess ciliary neurotrophic factor (CNTF) receptor complexes and can respond to CNTF; hence. we investigated the effects of BMSCs over-expressing CNTF on BL-injured RPE cells. BL-injured RPE cells were co-cultured with CNTF-BMSCs and GFP-BMSCs for 24 and 48 h. Superoxide dismutase and malondialdehyde assays were conducted to examine the effects of CNTF-BMSCs on the oxidative stress of RPE cells. VEGF protein secretion by RPE was determined by ELISA, and western blotting analysis was used to determine apoptotic protein expression and autophagic flux. Immunofluorescence was used to demonstrate the relationship between autophagy and apoptosis. We found that CNTF-BMSCs enhanced antioxidant capacity, decreased VEGF secretion, promoted autophagic flux, and inhibited apoptosis in BL-injured RPE cells, compared to GFP-BMSCs. Our findings suggest that CNTF over-expression enhances the protective effects of BMSCs on RPE cells, thus indicating subretinal-transplantation of CNTF-BMSCs may be a promising therapy for BL-injured retina.
C1 [Lin, Wen; Xu, Guoxing] FujianMed Univ, Dept Ophthalmol, Affiliated Hosp 1, 20 Chazhong Rd, Fuzhou 350005, Fujian, Peoples R China.
   [Xu, Guoxing] Fujian Inst Ophthalmol, Fuzhou, Fujian, Peoples R China.
RP Xu, GX (通讯作者)，FujianMed Univ, Dept Ophthalmol, Affiliated Hosp 1, 20 Chazhong Rd, Fuzhou 350005, Fujian, Peoples R China.; Xu, GX (通讯作者)，Fujian Inst Ophthalmol, Fuzhou, Fujian, Peoples R China.
EM xuguoxingfjmu@163.com
FU Chinese Nature Science Foundation [81770948]
FX This study was supported by the Chinese Nature Science Foundation (grant
   no. 81770948).
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NR 52
TC 2
Z9 3
U1 0
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1071-2690
EI 1543-706X
J9 IN VITRO CELL DEV-AN
JI In Vitro Cell. Dev. Biol.-Anim.
PD MAY
PY 2018
VL 54
IS 5
BP 355
EP 365
DI 10.1007/s11626-018-0243-9
PG 11
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA GE4PZ
UT WOS:000431199600004
PM 29564604
DA 2022-11-30
ER

PT J
AU Varin, M
   Kergoat, MJ
   Belleville, S
   Li, G
   Rousseau, J
   Roy-Gagnon, MH
   Moghadaszadeh, S
   Freeman, EE
AF Varin, Melanie
   Kergoat, Marie-Jeanne
   Belleville, Sylvie
   Li, Gisele
   Rousseau, Jacqueline
   Roy-Gagnon, Marie-Helene
   Moghadaszadeh, Solmaz
   Freeman, Ellen E.
TI Age-Related Eye Disease and Participation in Cognitive Activities
SO SCIENTIFIC REPORTS
LA English
DT Article
ID LOW-VISION REHABILITATION; OLDER-ADULTS; MACULAR DEGENERATION; VISUAL
   IMPAIRMENT; LIFE-STYLE; ALZHEIMER-DISEASE; GLAUCOMA; DECLINE;
   ENGAGEMENT; HEALTH
AB Studies have found a benefit to living a cognitively active life in older age. Our goal was to quantify participation in cognitively stimulating activities in adults with and without age-related eye disease. We conducted a cross-sectional hospital-based study in Montreal, Canada of older adults (n = 303) having either age-related macular degeneration (AMD) (n = 96), glaucoma (n = 93), or normal vision (n = 114). To be eligible, the AMD group had to have bilateral late stage AMD with a better eye visual acuity of 20/30 or worse. The glaucoma group had to have a diagnosis of bilateral primary open-angle glaucoma with visual field mean deviation < = -4 dB in their better eye. Further inclusion criteria included age >= 65 and a Mini-Mental State Exam Blind score >= 10. Cognitive activities were measured using the Victoria Longitudinal Study Activity Questionnaire. Linear regression was used. Patients with AMD (beta = -4.2, 95% confidence interval (CI) -6.0, -2.4) and glaucoma (beta = -1.8, 95% CI -3.3, -0.3) participated in fewer cognitive activities per month compared to those with normal vision after adjusting for age, sex, education, diabetes, number of comorbidities, cognition, and cataract. People with AMD and glaucoma participated in fewer cognitive activities, which could put them at risk for future cognitive impairment.
C1 [Varin, Melanie; Roy-Gagnon, Marie-Helene; Freeman, Ellen E.] Univ Ottawa, Sch Epidemiol & Publ Hlth, Ottawa, ON, Canada.
   [Kergoat, Marie-Jeanne; Belleville, Sylvie; Rousseau, Jacqueline] Inst Univ Geriatr Montreal, Ctr Rech, Montreal, PQ, Canada.
   [Li, Gisele; Moghadaszadeh, Solmaz; Freeman, Ellen E.] Hop Maison Neuve Rosemont, Ctr Rech, Montreal, PQ, Canada.
   [Li, Gisele; Freeman, Ellen E.] Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.
   [Freeman, Ellen E.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
C3 University of Ottawa; Universite de Montreal; Universite de Montreal;
   Universite de Montreal; University of Ottawa; Ottawa Hospital Research
   Institute
RP Freeman, EE (通讯作者)，Univ Ottawa, Sch Epidemiol & Publ Hlth, Ottawa, ON, Canada.; Freeman, EE (通讯作者)，Hop Maison Neuve Rosemont, Ctr Rech, Montreal, PQ, Canada.; Freeman, EE (通讯作者)，Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.; Freeman, EE (通讯作者)，Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
EM eefreeman@gmail.com
OI Roy-Gagnon, Marie-Helene/0000-0001-8747-0846
FU Canadian Institutes of Health Research [MOP 133560]
FX Funded by a grant from the Canadian Institutes of Health Research (MOP
   133560).
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NR 33
TC 11
Z9 11
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD DEC 21
PY 2017
VL 7
AR 17980
DI 10.1038/s41598-017-18419-2
PG 5
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Science & Technology - Other Topics
GA FQ7SE
UT WOS:000418562100020
PM 29269882
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Augustin, M
   Fialova, S
   Himmel, T
   Gloesmann, M
   Lengheimer, T
   Harper, DJ
   Plasenzotti, R
   Pircher, M
   Hitzenberger, CK
   Baumann, B
AF Augustin, Marco
   Fialova, Stanislava
   Himmel, Tanja
   Gloesmann, Martin
   Lengheimer, Theresia
   Harper, Danielle J.
   Plasenzotti, Roberto
   Pircher, Michael
   Hitzenberger, Christoph K.
   Baumann, Bernhard
TI Multi-Functional OCT Enables Longitudinal Study of Retinal Changes in a
   VLDLR Knockout Mouse Model
SO PLOS ONE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; SUBRETINAL
   NEOVASCULARIZATION; CHOROIDAL NEOVASCULARIZATION; ANGIOMATOUS
   PROLIFERATION; ANIMAL-MODEL; BLOOD-FLOW; HIGH-SPEED; HUMAN EYE;
   ANGIOGRAPHY
AB We present a multi-functional optical coherence tomography (OCT) imaging approach to study retinal changes in the very-low-density-lipoprotein-receptor (VLDLR) knockout mouse model with a threefold contrast. In the retinas of VLDLR knockout mice spontaneous retinal-chorodoidal neovascularizations form, having an appearance similar to choroidal and retinal neovascularizations (CNV and RNV) in neovascular age-related macular degeneration (AMD) or retinal angiomatous proliferation (RAP). For this longitudinal study, the mice were imaged every 4 to 6 weeks starting with an age of 4 weeks and following up to the age of 11 months. Significant retinal changes were identified by the multi-functional imaging approach offering a threefold contrast: reflectivity, polarization sensitivity (PS) and motion contrast based OCT angiography (OCTA). By use of this intrinsic contrast, the long-term development of neovascularizations was studied and associated processes, such as the migration of melanin pigments or retinal-choroidal anastomosis, were assessed in vivo. Furthermore, the in vivo imaging results were validated with histological sections at the endpoint of the experiment. Multi-functional OCT proves as a powerful tool for longitudinal retinal studies in preclinical research of ophthalmic diseases. Intrinsic contrast offered by the functional extensions of OCT might help to describe regulative processes in genetic animal models and potentially deepen the understanding of the pathogenesis of retinal diseases such as wet AMD.
C1 [Augustin, Marco; Fialova, Stanislava; Harper, Danielle J.; Pircher, Michael; Hitzenberger, Christoph K.; Baumann, Bernhard] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
   [Himmel, Tanja; Gloesmann, Martin] Univ Vet Med Vienna, Core Facil Res & Technol, Vienna, Austria.
   [Lengheimer, Theresia; Plasenzotti, Roberto] Med Univ Vienna, Div Biomed Res, Vienna, Austria.
C3 Medical University of Vienna; University of Veterinary Medicine Vienna;
   Medical University of Vienna
RP Augustin, M (通讯作者)，Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
EM marco.augustin@meduniwien.ac.at
RI plasenzotti, roberto/AAE-5049-2020; Himmel, Tanja/Q-2139-2019; Glösmann,
   Martin/F-9349-2019
OI plasenzotti, roberto/0000-0001-7652-1249; Himmel,
   Tanja/0000-0001-9443-8967; Glösmann, Martin/0000-0002-2094-3247;
   Baumann, Bernhard/0000-0001-6419-1932; Hitzenberger,
   Christoph/0000-0002-6608-8821; Michael, Pircher/0000-0001-9285-7527;
   Harper, Danielle J./0000-0003-2768-3684; Augustin,
   Marco/0000-0002-1019-0907
FU Austrian Science Fund (FWF) [P25823-B24]; European Research Council [ERC
   StG 640396 OPTIMALZ]
FX This work was funded by the Austrian Science Fund (FWF grant P25823-B24
   to BB; https://www.fwf.ac.at/) and the European Research Council (ERC
   StG 640396 OPTIMALZ to BB; https://erc.europa.eu/). 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 52
TC 32
Z9 32
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 OCT 6
PY 2016
VL 11
IS 10
AR e0164419
DI 10.1371/journal.pone.0164419
PG 20
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DZ2UR
UT WOS:000385697600126
PM 27711217
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Beato, J
   Pedrosa, AC
   Pinheiro-Costa, J
   Freitas-da-Costa, P
   Falcao, MS
   Melo, A
   Estrela-Silva, S
   Falcao-Reis, F
   Carneiro, AM
AF Beato, Joao
   Pedrosa, Ana Catarina
   Pinheiro-Costa, Joao
   Freitas-da-Costa, Paulo
   Falcao, Manuel S.
   Melo, Antonio
   Estrela-Silva, Sergio
   Falcao-Reis, Fernando
   Carneiro, Angela M.
TI Long-Term Effect of Anti-VEGF Agents on Ilntraocullar Pressure on
   Age-Rellated Macular Degeneration
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Intraocular pressure; Ocular
   hypertension; Neovascularization; Vascular endothelial growth factor
ID GROWTH-FACTOR INJECTIONS; INTRAOCULAR-PRESSURE; SUSTAINED ELEVATION;
   OCULAR HYPERTENSION; FACTOR THERAPY; INTRAVITREAL BEVACIZUMAB;
   RANIBIZUMAB; GLAUCOMA; PREDICTORS; EYES
AB Purpose: To analyze the effect of anti-vascular endothelial growth factor (VEGF) agents on intraocular pressure (IOP) in patients with neovascular age-related macular degeneration (AMD). Materials and Methods: This is a retrospective study that included 72 patients treated unilaterally with anti-VEGF agents according to a pro re nata regimen. Fellow non injected eyes (n = 72) were used as controls. IOP variation and the development of sustained ocular hypertension (OHT) were assessed both in the injected and in the fellow eyes. Results: While the final IOP was not significantly different between the 2 groups, sustained OHT developed in 4.2% of the injected eyes and 1.4% of the controls. In the study group, no significant IOP variation was noted during follow-up in patients receiving 20 injections, but there was a significant increase in IOP with time in more frequently treated patients (p = 0.041). Comparison of both subgroups demonstrated that patients receiving >20 injections suffered significantly greater IOP variation (p = 0.034) during follow-up, and that these patients tended to require IOP-lowering treatment more frequently (p = 0.090). Conclusion: Multiple anti-VEGF injections lead to an increase in IOP, although this variation is not sufficient to cause development of OHT in the majority of patients. (C) 2016 S. Karger AG, Basel
C1 [Beato, Joao; Pedrosa, Ana Catarina; Pinheiro-Costa, Joao; Freitas-da-Costa, Paulo; Falcao, Manuel S.; Melo, Antonio; Estrela-Silva, Sergio; Falcao-Reis, Fernando; Carneiro, Angela M.] Univ Porto, Hosp Sao Joao, Dept Ophthalmol, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
   [Pinheiro-Costa, Joao; Freitas-da-Costa, Paulo] Univ Porto, Fac Med, Dept Anat, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
   [Falcao, Manuel S.; Melo, Antonio; Falcao-Reis, Fernando; Carneiro, Angela M.] Univ Porto, Fac Med, Dept Sense Organs, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
C3 Sao Joao Hospital; Universidade do Porto; Universidade do Porto;
   Universidade do Porto
RP Beato, J (通讯作者)，Hosp Sao Joao, Dept Ophthalmol, P-4200319 Oporto, Portugal.
EM joao.nuno.beato@gmail.com
RI Falcao/AAQ-8509-2020; Carneiro, Angela/N-9680-2013
OI Falcao/0000-0003-4718-0910; Falcao-Reis, Fernando/0000-0002-5995-9430;
   Beato, Joao/0000-0003-3820-4597; Estrela Silva,
   Sergio/0000-0002-7415-813X; Freitas-da-Costa, Paulo/0000-0002-9567-4467;
   Carneiro, Angela/0000-0002-3370-7243
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NR 19
TC 6
Z9 6
U1 0
U2 3
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2016
VL 56
IS 1
BP 30
EP 34
DI 10.1159/000444395
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DN1FR
UT WOS:000376812200005
PM 27046391
OA Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Chitranshi, N
   Gupta, V
   Kumar, S
   Graham, SL
AF Chitranshi, Nitin
   Gupta, Vivek
   Kumar, Sanjay
   Graham, Stuart L.
TI Exploring the Molecular Interactions of 7,8-Dihydroxyflavone and Its
   Derivatives with TrkB and VEGFR2 Proteins
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE 7; 8-DHF; TrkB receptor; VEGFR2 receptor; docking; molecular dynamics;
   neurodegenerative disorder; retina; glaucoma; BDNF
ID GROWTH-FACTOR RECEPTORS; DYNAMICS SIMULATIONS; SIGNAL-TRANSDUCTION;
   RETINAL GANGLION; LIGAND; CELLS; ANGIOGENESIS; BINDING; INHIBITORS;
   VISUALIZATION
AB 7,8-Dihydroxyflavone (7,8-DHF) is a TrkB receptor agonist, and treatment with this flavonoid derivative brings about an enhanced TrkB phosphorylation and promotes downstream cellular signalling. Flavonoids are also known to exert an inhibitory effect on the vascular endothelial growth factor receptor (VEGFR) family of tyrosine kinase receptors. VEGFR2 is one of the important receptors involved in the regulation of vasculogenesis and angiogenesis and has also been implicated to exhibit various neuroprotective roles. Its upregulation and uncontrolled activity is associated with a range of pathological conditions such as age-related macular degeneration and various proliferative disorders. In this study, we investigated molecular interactions of 7,8-DHF and its derivatives with both the TrkB receptor as well as VEGFR2. Using a combination of molecular docking and computational mapping tools involving molecular dynamics approaches we have elucidated additional residues and binding energies involved in 7,8-DHF interactions with the TrkB Ig2 domain and VEGFR2. Our investigations have revealed for the first time that 7,8-DHF has dual biochemical action and its treatment may have divergent effects on the TrkB via its extracellular Ig2 domain and on the VEGFR2 receptor through the intracellular kinase domain. Contrary to its agonistic effects on the TrkB receptor, 7,8-DHF was found to downregulate VEGFR2 phosphorylation both in 661W photoreceptor cells and in retinal tissue.
C1 [Chitranshi, Nitin; Gupta, Vivek; Graham, Stuart L.] Macquarie Univ, Fac Med & Hlth Sci, N Ryde, NSW 2109, Australia.
   [Kumar, Sanjay] Bioinformat Ctr, Lucknow 226021, Uttar Pradesh, India.
   [Graham, Stuart L.] Univ Sydney, Save Sight Inst, Sydney, NSW 2109, Australia.
C3 Macquarie University; University of Sydney
RP Chitranshi, N (通讯作者)，Macquarie Univ, Fac Med & Hlth Sci, F10A,2 Technol Pl, N Ryde, NSW 2109, Australia.
EM nitin.chitranshi@students.mq.edu.au; vivek.gupta@mq.edu.au;
   sanjjaybharti@gmail.com; stuart.graham@mq.edu.au
RI Gupta, Vivek Kumar/AAB-8940-2022; Chitranshi, Nitin/AAK-8831-2020
OI Kumar, Sanjay/0000-0002-5950-3716; Graham, Stuart/0000-0001-7519-969X;
   Gupta, Vivek/0000-0002-0202-7843; Chitranshi, Nitin/0000-0002-6508-9865
FU Bayer pharmaceuticals, Australia; ORIA (Ophthalmic Research Institute)
   Australia; NHMRC (National Health and Medical Research Council)
   Australia; Allergan Australia; iMQRES scholarship
FX We acknowledge the support from Bayer pharmaceuticals, Australia, ORIA
   (Ophthalmic Research Institute) Australia and NHMRC (National Health and
   Medical Research Council) Australia. Vivek Gupta supported by Allergan
   Australia. Nitin Chitranshi acknowledges support from an iMQRES
   scholarship.
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NR 52
TC 33
Z9 33
U1 1
U2 17
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 SEP
PY 2015
VL 16
IS 9
BP 21087
EP 21108
DI 10.3390/ijms160921087
PG 22
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA CV8MD
UT WOS:000364541000054
PM 26404256
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Toriyama, Y
   Iesato, Y
   Imai, A
   Sakurai, T
   Kamiyoshi, A
   Ichikawa-Shindo, Y
   Kawate, H
   Yamauchi, A
   Igarashi, K
   Tanaka, M
   Liu, T
   Xian, X
   Zhai, LY
   Owa, S
   Murata, T
   Shindo, T
AF Toriyama, Yuichi
   Iesato, Yasuhiro
   Imai, Akira
   Sakurai, Takayuki
   Kamiyoshi, Akiko
   Ichikawa-Shindo, Yuka
   Kawate, Hisaka
   Yamauchi, Akihiro
   Igarashi, Kyoko
   Tanaka, Megumu
   Liu, Tian
   Xian, Xian
   Zhai, Liuyu
   Owa, Shinji
   Murata, Toshinori
   Shindo, Takayuki
TI Pathophysiological Function of Endogenous Calcitonin Gene-Related
   Peptide in Ocular Vascular Diseases
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID OXYGEN-INDUCED RETINOPATHY; CHOROIDAL NEOVASCULARIZATION;
   ADRENOMEDULLIN-RAMP2 SYSTEM; MICE; ANGIOGENESIS; INFLAMMATION;
   FACILITATION; INTEGRITY; ISCHEMIA; FIBROSIS
AB Calcitonin gene-related peptide (CGRP; official name CALCA) has a variety of functions and exhibits both angiogenic and anti-inflammatory properties. We previously reported the angiogenic effects of the CGRP family peptide adrenomedullin in oxygen-induced retinopathy; however, the effects of CGRP on ocular angiogenesis remain unknown. Herein, we used CGRP knockout (CGRP(-/-)) mice to investigate the roles of CGRP in ocular vascular disease. Observation of pathological retinal angiogenesis in the oxygen-induced retinopathy model revealed no difference between CGRP(-/-) and wild-type mice. However, much higher Levels of the CGRP receptor were present in the choroid than the retina. Laser-induced choroidal neovascularization (CNV), a model of exudative age-related macular degeneration, revealed more severe CNV Lesions in CGRP(-/-) than wild-type mice, and fluorescein angiography showed greater leakage from CNV in CGRP(-/-). In addition, macrophage infiltration and tumor necrosis factor (TNF)-alpha production were enhanced within the CNV lesions in CGRP(-/-) mice, and the TNF-alpha, in turn, suppressed the barrier formation of retinal pigment epithelial cells. In vivo, CGRP administration suppressed CNV formation, and CGRP also dose dependently suppressed TNF-alpha production by isolated macrophages. From these data, we conclude that CGRP suppresses the development of leaky CNV through negative regulation of inflammation. CGRP may thus be a promising therapeutic agent for the treatment of ocular vascular diseases associated with inflammation.
C1 [Toriyama, Yuichi; Iesato, Yasuhiro; Imai, Akira; Sakurai, Takayuki; Kamiyoshi, Akiko; Ichikawa-Shindo, Yuka; Kawate, Hisaka; Yamauchi, Akihiro; Igarashi, Kyoko; Tanaka, Megumu; Liu, Tian; Xian, Xian; Zhai, Liuyu; Owa, Shinji; Shindo, Takayuki] Shinshu Univ, Grad Sch Med, Dept Cardiovasc Dis, Matsumoto, Nagano 3908621, Japan.
   [Toriyama, Yuichi; Iesato, Yasuhiro; Imai, Akira; Murata, Toshinori] Shinshu Univ, Sch Med, Dept Ophthalmol, Matsumoto, Nagano 3908621, Japan.
C3 Shinshu University; Shinshu University
RP Shindo, T (通讯作者)，Shinshu Univ, Grad Sch Med, Dept Cardiovasc Dis, Asahi 3-1-1, Matsumoto, Nagano 3908621, Japan.
EM tshindo@shinshu-u.ac.jp
RI Xian, Xunde/B-9490-2012
OI Xian, Xunde/0000-0003-3059-1254
FU Cabinet Office, Government of Japan; Funding Program for Next Generation
   World-Leading Researchers (NEXT Program); (KAKENHI), the Japan Science
   and Technology Agency CREST; National Cardiovascular Center research
   grant for cardiovascular diseases; Novartis Foundation for
   Gerontological Research; Ichiro Kanehara Foundation; Cosmetology
   Research Foundation; SENSHIN Medical Research Foundation; Nagao Memorial
   Fund research grant; Kanzawa Medical Research Foundation; Ono Medical
   Research Foundation; Nakatomi Foundation; Japan Heart Foundation;
   Astellas/Pfizer; Research Foundation for Opto-Science and Technology;
   Japan Vascular Disease Research Foundation; Takeda Science Foundation
FX Supported by the Cabinet Office, Government of Japan, Funding Program
   for Next Generation World-Leading Researchers (NEXT Program), a
   Grant-in-Aid for Scientific Research (KAKENHI), the Japan Science and
   Technology Agency CREST, a National Cardiovascular Center research grant
   for cardiovascular diseases, and the Novartis Foundation for
   Gerontological Research research grant, the Ichiro Kanehara Foundation
   research grant, the Cosmetology Research Foundation research grant,
   SENSHIN Medical Research Foundation research grant, Nagao Memorial Fund
   research grant, Kanzawa Medical Research Foundation research grant, Ono
   Medical Research Foundation research grant, the Nakatomi Foundation
   research grant, the Japan Heart Foundation and Astellas/Pfizer grant for
   research on atherosclerosis update, the Research Foundation for
   Opto-Science and Technology research grant, the Japan Vascular Disease
   Research Foundation research grant, and Takeda Science Foundation
   research grant.
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NR 38
TC 9
Z9 10
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2015
VL 185
IS 6
BP 1783
EP 1794
DI 10.1016/j.ajpath.2015.02.017
PG 12
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA CJ2YL
UT WOS:000355350500025
PM 25857228
OA Green Submitted, Bronze
DA 2022-11-30
ER

PT J
AU Lyzogubov, V
   Wu, X
   Jha, P
   Tytarenko, R
   Triebwasser, M
   Kolar, G
   Bertram, P
   Bora, PS
   Atkinson, JP
   Bora, NS
AF Lyzogubov, Valeriy
   Wu, Xiaobo
   Jha, Purushottam
   Tytarenko, Ruslana
   Triebwasser, Michael
   Kolar, Grant
   Bertram, Paula
   Bora, Puran S.
   Atkinson, John P.
   Bora, Nalini S.
TI Complement Regulatory Protein CD46 Protects against Choroidal
   Neovascularization in Mice
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MEMBRANE ATTACK COMPLEX; MACULAR DEGENERATION; MOUSE MODEL;
   RISK-FACTORS; ACTIVATION; MCP; LOCALIZATION; EXPRESSION; GROWTH; CELLS
AB Dysregulation of the complement system is increasingly recognized as a contributing factor in age-related macular degeneration. Although the complement regulator CD46 is expressed ubiquitously in humans, in mouse it was previously thought to be expressed only on spermatozoa. We detected CD46 mRNA and protein in the posterior ocular segment (neuronal retina, retinal pigment epithelium, and choroid) of wild-type (WT) C57BL/6J mice. Cd46(-/-) knockout mice exhibited increased levels of the membrane attack complex and of vascular endothelial growth factor (VEGF) in the retina and choroid. The Cd46(-/-) mice were also more susceptible to laser-induced choroidal neovascularization (CNV). In Cd46(-/-) mice, 19% of laser spots were positive for CNV at day 2 after treatment, but no positive spots were detected in WT mice. At day 3, 42% of laser spots were positive in Cd46(-/-) mice, but only 11% in WT mice. A fully developed CNV complex was noted in both Cd46(-/-) and WT mice at day 7; however, lesion size was significantly (P < 0.05) increased in Cd46(-/-) mice. Our findings provide evidence for expression of CD46 in the mouse eye and a role for CD46 in protection against laser-induced CNV. We propose that the Cd46(-/-) mouse has a greater susceptibility to experimental CNV because of insufficient complement inhibition, which leads to increased membrane attack complex deposition and VEGF expression.
C1 [Lyzogubov, Valeriy; Jha, Purushottam; Tytarenko, Ruslana; Bora, Puran S.; Bora, Nalini S.] Univ Arkansas Med Sci, Dept Ophthalmol, Jones Eye Inst, Pat & Willard Walker Eye Res Ctr, Little Rock, AR 72205 USA.
   [Wu, Xiaobo; Triebwasser, Michael; Kolar, Grant; Bertram, Paula; Atkinson, John P.] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA.
   [Kolar, Grant] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
C3 University of Arkansas System; University of Arkansas Medical Sciences;
   Washington University (WUSTL); Washington University (WUSTL)
RP Bora, NS (通讯作者)，Univ Arkansas Med Sci, Dept Ophthalmol, Jones Eye Inst, 4301 W Markham,523-7, Little Rock, AR 72205 USA.
EM nbora@uams.edu
OI Bora, Puran/0000-0003-4781-1217
FU Edward N. & Della L. Thome Memorial Foundation; Lions of Arkansas
   Foundation; Pat and Willard Walker Eye Research Center-Harvey & Bernice
   Jones Eye Institute; NIH [R01-AI041592, R01-GM099111, P20-RR016460,
   P30-DK052574]; Protein Production and Purification Core
   Facility-Rheumatic Diseases Core Center [P30-AR048335]; NATIONAL CENTER
   FOR RESEARCH RESOURCES [P20RR016460] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI041592]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ARTHRITIS AND
   MUSCULOSKELETAL AND SKIN DISEASES [P30AR048335] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY
   DISEASES [P30DK052574] Funding Source: NIH RePORTER; NATIONAL INSTITUTE
   OF GENERAL MEDICAL SCIENCES [R01GM099111] Funding Source: NIH RePORTER
FX Supported by grants from the Edward N. & Della L. Thome Memorial
   Foundation, the Lions of Arkansas Foundation, and the Pat and Willard
   Walker Eye Research Center-Harvey & Bernice Jones Eye Institute and by
   NIH grants R01-AI041592 (J.P.A.), R01-GM099111 (J.P.A.), P20-RR016460
   (Digital Microscopy Core), P30-DK052574 (Morphology Core), and
   P30-AR048335 (Protein Production and Purification Core
   Facility-Rheumatic Diseases Core Center).
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NR 49
TC 22
Z9 23
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD SEP
PY 2014
VL 184
IS 9
BP 2537
EP 2548
DI 10.1016/j.ajpath.2014.06.001
PG 12
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA AO4CN
UT WOS:000341283900018
PM 25019227
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Shmueli, RB
   Sunshine, JC
   Xu, ZH
   Duh, EJ
   Green, JJ
AF Shmueli, Ron B.
   Sunshine, Joel C.
   Xu, Zhenhua
   Duh, Elia J.
   Green, Jordan J.
TI Gene delivery nanoparticles specific for human microvasculature and
   macrovasculature
SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
LA English
DT Article
DE Nonviral gene delivery; Nanoparticles; Ocular diseases; Human retinal
   endothelial cells
ID ENDOTHELIAL-CELLS; EXPRESSION; VECTORS; THERAPY
AB Endothelial cell dysfunction is a critical component of ocular diseases such as age-related macular degeneration and diabetic retinopathy. An important limitation in endothelial cell research is the difficulty in achieving efficient transfection of these cells. A new polymer library was here synthesized and utilized to find polymeric nanoparticles that can transfect macrovascular (human umbilical vein, HUVECs) and microvascular (human retinal, HRECs) endothelial cells. Nanoparticles were synthesized that can achieve transfection efficiency of up to 85% for HRECs and 65% for HUVECs. These nanoparticle systems enable high levels of expression while avoiding problems associated with viral gene delivery. The polymeric nanoparticles also show cell-specific behavior, with a high correlation between microvascular and macrovascular transfection (R-2 = 0.81) but low correlation between retinal endothelial and retinal epithelial transfection (R-2 = 0.21). These polymeric nanoparticles can be used in vitro as experimental tools and potentially in vivo to target and treat vascular-specific diseases.
   From the Clinical Editor: Polymeric nanoparticles were synthesized with the goal of transfecting endothelial cells, which are commonly considered difficult targets. The authors report excellent transfection efficiency of up to 85% for human retinal and 65% for human umbilical vein endothelial cells. These NPs can be used in vitro as experimental tools and potentially in vivo to target and treat vascular-specific diseases. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Shmueli, Ron B.; Sunshine, Joel C.; Green, Jordan J.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21231 USA.
   [Xu, Zhenhua; Duh, Elia J.; Green, Jordan J.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21231 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins
   Medicine
RP Green, JJ (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21231 USA.
EM green@jhu.edu
RI Green, Jordan/B-9001-2009
OI Green, Jordan/0000-0003-4176-3808; Sunshine, Joel/0000-0001-9987-6712
FU Maryland Technology Development Corporation-Maryland Stem Cell Research
   Fund [2009-MSCRFE-0098-00]; National Institutes of Health [R21CA152473];
   Medical Scientist Training Program; Career Development Award from
   Research to Prevent Blindness; NATIONAL CANCER INSTITUTE [R21CA152473]
   Funding Source: NIH RePORTER
FX The work was supported in part by the Maryland Technology Development
   Corporation-Maryland Stem Cell Research Fund (2009-MSCRFE-0098-00), the
   National Institutes of Health (R21CA152473), and the Medical Scientist
   Training Program (to J.C.S.). E.J.D. is supported by a Career
   Development Award from Research to Prevent Blindness.
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NR 24
TC 35
Z9 35
U1 3
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1549-9634
J9 NANOMED-NANOTECHNOL
JI Nanomed.-Nanotechnol. Biol. Med.
PD OCT
PY 2012
VL 8
IS 7
BP 1200
EP 1207
DI 10.1016/j.nano.2012.01.006
PG 8
WC Nanoscience & Nanotechnology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics; Research & Experimental Medicine
GA 012DS
UT WOS:000309216300018
PM 22306159
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Vaclavik, V
   Tran, HV
   Gaillard, MC
   Schorderet, DF
   Munier, FL
AF Vaclavik, Veronika
   Tran, Hoai V.
   Gaillard, Marie-Claire
   Schorderet, Daniel F.
   Munier, Francis L.
TI PATTERN DYSTROPHY WITH HIGH INTRAFAMILIAL VARIABILITY ASSOCIATED WITH
   Y141C MUTATION IN THE PERIPHERIN/RDS GENE AND SUCCESSFUL TREATMENT OF
   SUBFOVEAL CNV RELATED TO MULTIFOCAL PATTERN TYPE WITH ANTI-VEGF
   (RANIBIZUMAB) INTRAVITREAL INJECTIONS
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE pattern dystrophy; peripherin/RDS; choroidal neovascularization;
   anti-VEGF treatment; ranibizumab; lucentis
ID FOVEOMACULAR VITELLIFORM DYSTROPHY; RETINAL-PIGMENT EPITHELIUM; CONE-ROD
   DYSTROPHY; DEGENERATION SLOW RDS; CHOROIDAL NEOVASCULARIZATION;
   RETINITIS-PIGMENTOSA; PHOTODYNAMIC THERAPY; PHENOTYPIC VARIATION;
   RETICULAR DYSTROPHY; MACULAR DYSTROPHY
AB Objective: To identify disease causing mutation in three generations of a Swiss family with pattern dystrophy and high intrafamilial variability of phenotype. To assess the effect of intravitreal ranibizumab injections in the treatment of subfoveal choroidal neovascularization associated with pattern dystrophy in one patient.
   Methods: Affected family members were ascertained for phenotypic and genotypic characterization. Ophthalmic evaluations included fundus photography, autofluorescence imaging, optical coherence tomography, and International Society for Clinical Electrophysiology of Vision standard full-field electroretinography. When possible family members had genetic testing. The proband presented with choroidal neovascularization and had intravitreal injections as needed according to visual acuity and optical coherence tomography.
   Results: Proband had a multifocal type pattern dystrophy, and his choroidal neovascularization regressed after four intravitreal injections. The vision improved from 0.8 to 1.0, and optical coherence tomography showed complete anatomical restoration. A butterfly-shaped pattern was observed in her cousin, whereas a fundus pulverulentus pattern was seen in a second cousin. Aunt had a multifocal atrophic appearance, simulating geographic atrophy in age-related macular degeneration. The Y141C mutation was identified in the peripherin/RDS gene and segregated with disease in the family.
   Conclusion: This is the first report of marked intrafamilial variation of pattern dystrophy because of peripherin/RDS Y141C mutation. Intravitreal ranibizumab injections might be a valuable treatment for associated subfoveal choroidal neovascularization. RETINA 32:1942-1949, 2012
C1 [Vaclavik, Veronika; Tran, Hoai V.; Gaillard, Marie-Claire; Munier, Francis L.] Hop Ophtalm Jules Gonin, CH-1004 Lausanne, Switzerland.
   [Vaclavik, Veronika] Clin Ophtalmol Univ, HUG, Geneva, Switzerland.
   [Schorderet, Daniel F.; Munier, Francis L.] IRO, Sion, Switzerland.
   [Schorderet, Daniel F.] Univ Lausanne, Fac Biol & Med, Lausanne, Switzerland.
   [Schorderet, Daniel F.] Ecole Polytech Fed Lausanne, Fac Life Sci, Lausanne, Switzerland.
C3 University of Geneva; University of Lausanne; Swiss Federal Institutes
   of Technology Domain; Ecole Polytechnique Federale de Lausanne
RP Vaclavik, V (通讯作者)，Hop Ophtalm Jules Gonin, Ave France 15, CH-1004 Lausanne, Switzerland.
EM veronika.vaclavik@fa2.ch
CR [Anonymous], 1997, DIAGNOSIS TREATMENT
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NR 39
TC 27
Z9 27
U1 0
U2 3
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 OCT
PY 2012
VL 32
IS 9
BP 1942
EP 1949
DI 10.1097/IAE.0b013e31824b32e4
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 012EH
UT WOS:000309217800030
PM 22466463
DA 2022-11-30
ER

PT J
AU Dong, A
   Xie, B
   Shen, J
   Yoshida, T
   Yokoi, K
   Hackett, SF
   Campochiaro, PA
AF Dong, Aling
   Xie, Bing
   Shen, Jikui
   Yoshida, Tsunehiko
   Yokoi, Katsutoshi
   Hackett, Sean F.
   Campochiaro, Peter A.
TI Oxidative Stress Promotes Ocular Neovascularization
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL NEOVASCULARIZATION; INCREASED
   EXPRESSION; MODEL; MICE; RANIBIZUMAB; RETINOPATHY; OXIDASE; DRUSEN; VEGF
AB Mice deficient in superoxide dismutase / (Sod I-/- mice) develop many features seen in patients with age-related macular degeneration (AMD) including choroidal neovascularization (NV). We sought to determine if the absence of SOD I contributes to the pro-angiogenic environment in the subretinal space or whether it is completely secondary to other changes in Bruch's membrane and the retinal pigmented epithelium (RPE) that precede the development of choroidal NV. In an ischemic retinopathy model or a transgenic model in which the rhodopsin promoter drives expression of vascular endothelial growth factor (VEGF) in photoreceptor there was significantly more NV in Sod I-/- compared to Sod I+/+ mice. The compromised antioxidant defense system in Sod I-/- mice contributes to the proangiogenic environment, because treatment of Sod I-/- mice with a mixture of antioxidants caused a significant reduction in ischemia-induced retinal NV. Wild-type mice treated with the same antioxidants also showed reduced ischemia-induced retinal NV, reduced VEGF-induced subretinal NV, and reduced choroidal NV at Bruch's membrane rupture sites. These data suggest that reactive oxygen species contribute to several types of ocular NV. This could explain why in the Age-Related Eye Disease Trial, antioxidant treatment reduced conversion from non-neovascular to neovascular AMD and severe vision loss, and suggest that potent antioxidants should be considered for other diseases complicated by ocular NV.
C1 [Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA.
   Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins University
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Maumenee 719,600 N Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhmi.edu
OI Xie, Bing/0000-0003-2335-5966
FU NEI (National Eye Institute) [EY05951, EY12609, P30EY1765]; NATIONAL EYE
   INSTITUTE [P30EY001765, R01EY005951, R01EY012609] Funding Source: NIH
   RePORTER
FX Contract grant sponsor: NEI (National Eye Institute);; Contract grant
   numbers: EY05951, EY12609, P30EY1765.
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NR 27
TC 104
Z9 113
U1 1
U2 12
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9541
EI 1097-4652
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD JUN
PY 2009
VL 219
IS 3
BP 544
EP 552
DI 10.1002/jcp.21698
PG 9
WC Cell Biology; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Physiology
GA 438IA
UT WOS:000265547900006
PM 19142872
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Izumi-Nagai, K
   Nagai, N
   Ohgami, K
   Satofuka, S
   Ozawa, Y
   Tsubota, K
   Umezawa, K
   Ohno, S
   Oike, Y
   Ishida, S
AF Izumi-Nagai, Kanako
   Nagai, Norihiro
   Ohgami, Kazuhiro
   Satofuka, Shingo
   Ozawa, Yoko
   Tsubota, Kazuo
   Umezawa, Kazuo
   Ohno, Shigeaki
   Oike, Yuichi
   Ishida, Susumu
TI Macular pigment lutein is antiinflammatory in preventing Choroidal
   neovascularization
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE choroidal neovascularization; lutein; inflammation; nuclear factor-kappa
   B; age-relatedmacular degeneration
ID NF-KAPPA-B; AGE-RELATED MACULOPATHY; ENDOTHELIAL GROWTH-FACTOR; II
   TYPE-1 RECEPTOR; BIOLOGICAL-ACTIVITIES; DEGENERATION; ZEAXANTHIN;
   ATHEROSCLEROSIS; SUPPLEMENTATION; INFLAMMATION
AB Background-Choroidal neovascularization (CNV) is a critical pathogenesis in age-related macular degeneration, the most common cause of blindness in the developed countries. The aim of the current study was to investigate the effect of lutein supplementation on the development of the murine model of laser-induced CNV together with underlying molecular mechanisms.
   Methods and Results-Mice were orally pretreated with lutein daily from 3 days before laser photocoagulation untill the end of the study. The index of CNV volume was significantly suppressed by the treatment with lutein, compared with vehicle-treated animals. Lutein treatment led to significant inhibition of macrophage infiltration into CNV and of the in vivo and in vitro expression of inflammation-related molecules including vascular endothelial growth factor, monocyte chemotactic protein-1, and intercellular adhesion molecule-1. Importantly, lutein suppressed I kappa B-alpha degradation and nuclear translocation of nuclear factor (NF)-kappa Bp65 both in vivo and in vitro. Additionally, the development of CNV was significantly suppressed by inhibiting NF-kappa B p65 nuclear translocation, to the levels seen in the lutein treatment.
   Conclusions-Lutein treatment led to significant suppression of CNV development together with inflammatory processes including NF-kappa B activation and subsequent upregulation of inflammatory molecules, providing molecular evidence of potential validity of lutein supplementation as a therapeutic strategy to suppress CNV.
C1 Keio Univ, Sch Med, Dept Ophthalmol, Lab Retinal Cell Biol,Shinjuku Ku, Tokyo 1608582, Japan.
   Hokkaido Univ, Grad Sch Med, Dept Optometry & Vis Sci, Sapporo, Hokkaido, Japan.
   Keio Univ, Fac Sci & Technol, Dept Appl Chem, Yokohama, Kanagawa 223, Japan.
   Kumamoto Univ, Grad Sch Med Sci, Dept Mol Genet, Kumamoto, Japan.
C3 Keio University; Hokkaido University; Keio University; Kumamoto
   University
RP Ishida, S (通讯作者)，Keio Univ, Sch Med, Dept Ophthalmol, Lab Retinal Cell Biol,Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
EM ishidasu@sc.itc.keio.ac.jp
RI ISHIDA, SUSUMU/D-7067-2012; Ozawa, Yoko/AAH-9888-2020
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NR 39
TC 118
Z9 129
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD DEC
PY 2007
VL 27
IS 12
BP 2555
EP 2562
DI 10.1161/ATVBAHA.107.151431
PG 8
WC Hematology; Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Hematology; Cardiovascular System & Cardiology
GA 234EK
UT WOS:000251143300013
PM 17932319
OA Bronze
DA 2022-11-30
ER

PT J
AU Ikeda, Y
   Yonemitsu, Y
   Onimaru, M
   Nakano, T
   Miyazaki, M
   Kohno, R
   Nakagawa, K
   Ueno, A
   Sueishi, K
   Ishibashi, T
AF Ikeda, Yasuhiro
   Yonemitsu, Yoshikazu
   Onimaru, Mitsuho
   Nakano, Toshiaki
   Miyazaki, Masanori
   Kohno, Ri-Ichiro
   Nakagawa, Kazunori
   Ueno, Akifumi
   Sueishi, Katsuo
   Ishibashi, Tatsuro
TI The regulation of vascular endothelial growth factors (VEGF-A -C, and
   -D) expression in the retinal pigment epithelium
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retinal pigment epithelium; hypoxia; cell-cell adhesion; cell-matrix
   adhesion
ID CHOROIDAL NEOVASCULAR MEMBRANES; ANGIOGENESIS IN-VIVO; MACULAR
   DEGENERATION; PERMEABILITY FACTOR; TRANSGENIC MICE; HUMAN PLACENTA;
   CELLS; RECEPTOR; HYPOXIA; LYMPHANGIOGENESIS
AB The vascular endothelial growth factor (VEGF) family plays an essential role in vascular development, angiogenesis and lymphangiogenesis. VEGF-A is a key regulator of endothelial cell functions and VEGF-C and VEGF-D are known to stimulate both angiogenesis and lymphangiogenesis. In a surgically removed subretinal vascular membrane of an age-related macular degeneration (AMD) patient, both VEGF-C and VEGF-D were confirmed. in addition to VEGF-A, to be markedly positive in the retinal pigment epithelium (RPE). There is no lymph vessel in ocular tissue, so it is possible that VEGF-C and VEGF-D expression in the RPE play some role in ocular angiogenesis, as well as VEGF-A. Next, we assessed the transition of VEGF-A, -C, and -D expression on several conditions, in human RPE. Hypoxia proverbially induced VEGF-A mRNA expression, meanwhile VEGF-C and VEGF-D mRNA expression was down-regulated. The Ca2+ deprivation from culture medium strongly up-regulated VEGF-A and VEGF-D mRNA expression. Culture on plastic flasks precoated with poly-2-hydroxyethyl methacrylate up-regulated VEGF-D expression. Meanwhile, no significant change of VEGF-C mRNA expression was found in the blockade of cell-cell and/or cell-matrix adhesion. These findings suggest the possibility that VEGF-C and VEGF-D expression in RPE modify the ocular angiogenesis as angiogenic stimulators. (c) 2006 Elsevier Ltd. All rights reserved.
C1 Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan.
   Kyushu Univ, Grad Sch Med Sci, Dept Pathol, Div Pathophysiol & Expt Pathol, Fukuoka 812, Japan.
C3 Kyushu University; Kyushu University
RP Ikeda, Y (通讯作者)，Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
EM ymocl@pathol1.med.kyushu-u.ac.jp
CR Achen MG, 1998, P NATL ACAD SCI USA, V95, P548, DOI 10.1073/pnas.95.2.548
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NR 41
TC 39
Z9 39
U1 0
U2 3
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 1031
EP 1040
DI 10.1016/j.exer.2006.05.007
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 093WZ
UT WOS:000241202300004
PM 16842779
DA 2022-11-30
ER

PT J
AU Taylor, HR
   Keeffe, JE
   Vu, HTV
   Wang, JJ
   Rochtchina, E
   Pezzullo, ML
   Mitchell, P
AF Taylor, HR
   Keeffe, JE
   Vu, HTV
   Wang, JJ
   Rochtchina, E
   Pezzullo, ML
   Mitchell, P
TI Vision loss in Australia
SO MEDICAL JOURNAL OF AUSTRALIA
LA English
DT Article
ID BILATERAL VISUAL IMPAIRMENT; PREVALENCE
AB Objective: To assess the prevalence and causes of vision loss in Australia and to project these data into the future.
   Design: Synthesis of data from two cross-sectional population-based cohort studies the Melbourne Visual Impairment Project and the Blue Mountains Eye Study - and extrapolation to the entire Australian population.
   Setting and participants: 8376 community and 533 nursing home residents recruited between 1992 and 1996 in urban and rural Victoria and New South Wales. Main outcome measures: Age-standardised prevalence of low vision (visual acuity < 6/12) and blindness (visual acuity < 6/60) (both measured in the best eye, with spectacles if usually worn for distance vision), and their causes for the Australian population for 2000 to 2024, projected from Australian Bureau of Statistics population data.
   Results: In 2004, 480 300 Australians were estimated to have low vision, including 50600 with blindness. The most common causes of low vision were undercorrected refractive error (62%), cataract (14%) and age-related macular degeneration (10%). The latter was responsible for almost half of all cases of blindness. The numbers of people with low vision and blindness are projected to almost double by 2024.
   Conclusions: Vision loss in Australia is a much bigger problem than is usually recognised; 76% of low vision is caused by uncorrected refractive error or cataract, both readily treatable. However, the prevention and treatment of macular degeneration poses a major challenge.
C1 Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.
   Univ Sydney, Ctr Vis Res, Sydney, NSW 2006, Australia.
   Access Econ, Canberra, ACT, Australia.
C3 Centre for Eye Research Australia; University of Melbourne; University
   of Sydney
RP Taylor, HR (通讯作者)，Univ Melbourne, Ctr Eye Res Australia, Locked Bag 8, Melbourne, Vic 3002, Australia.
EM h.taylor@unimelb.edu.au
RI wang, jie/GRS-0942-2022; Mitchell, Paul/P-1498-2014; Wang, Jie
   Jin/P-1499-2014
OI Wang, Jie Jin/0000-0001-9491-4898; Taylor, Hugh/0000-0002-9437-784X
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NR 14
TC 179
Z9 179
U1 0
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0025-729X
EI 1326-5377
J9 MED J AUSTRALIA
JI Med. J. Aust.
PD JUN 6
PY 2005
VL 182
IS 11
BP 565
EP 568
DI 10.5694/j.1326-5377.2005.tb06815.x
PG 4
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 948CE
UT WOS:000230692800009
PM 15938683
DA 2022-11-30
ER

PT J
AU Kikuchi, Y
   Sugano, E
   Yuki, S
   Tabata, K
   Endo, Y
   Takita, Y
   Onoguchi, R
   Ozaki, T
   Fukuda, T
   Takai, Y
   Kurose, T
   Tanaka, K
   Honma, Y
   Perez, E
   Stock, M
   Fernandez, JR
   Tamura, M
   Voronkov, M
   Stock, JB
   Tomita, H
AF Kikuchi, Yuki
   Sugano, Eriko
   Yuki, Shiori
   Tabata, Kitako
   Endo, Yuka
   Takita, Yuya
   Onoguchi, Reina
   Ozaki, Taku
   Fukuda, Tomokazu
   Takai, Yoshihiro
   Kurose, Takahiro
   Tanaka, Koichi
   Honma, Yoichi
   Perez, Eduardo
   Stock, Maxwell
   Fernandez, Jose R.
   Tamura, Masanori
   Voronkov, Michael
   Stock, Jeffry B.
   Tomita, Hiroshi
TI SIG-1451, a Novel, Non-Steroidal Anti-Inflammatory Compound, Attenuates
   Light-Induced Photoreceptor Degeneration by Affecting the Inflammatory
   Process
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration; light-induced photoreceptor
   degeneration; anti-inflammatory drug; Toll-like receptor 4
ID NF-KAPPA-B; RETINAL DEGENERATION; MACULAR DEGENERATION;
   COMPLEMENT-SYSTEM; MULLER CELLS; EXPRESSION; MICROGLIA; ACCUMULATION;
   MITOCHONDRIA; PREVALENCE
AB Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory compound developed for treating atopic dermatitis and known to inhibit Toll-like receptor 4, in light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once per day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 partially protected against this decrease in retinal thickness and increase in ERG amplitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Muller cells. The upregulation of C-C motif chemokine 2 by LPS stimulation was significantly inhibited by SIG-1451 treatment, and Western blot analysis revealed a decrease in phosphorylated I-kappa B levels. These results indicate that SIG-1451 indirectly protects photoreceptor cells by attenuating light damage progression, by affecting the inflammatory responses.
C1 [Kikuchi, Yuki; Sugano, Eriko; Yuki, Shiori; Tabata, Kitako; Endo, Yuka; Takita, Yuya; Onoguchi, Reina; Ozaki, Taku; Fukuda, Tomokazu; Tomita, Hiroshi] Iwate Univ, Lab Visual Neurosci, Grad Course Biol Sci, Div Sci & Engn, 4-3-5 Ueda, Morioka, Iwate 0208551, Japan.
   [Takai, Yoshihiro; Kurose, Takahiro; Tanaka, Koichi; Honma, Yoichi] Rohto Pharmaceut Co Ltd, 6-5-4 Kunimidai, Kizugawa, Kyoto 6190216, Japan.
   [Perez, Eduardo; Stock, Maxwell; Fernandez, Jose R.; Tamura, Masanori; Voronkov, Michael] Signum Biosci, 4999 Pearl East Circle, Boulder, CO 80301 USA.
   [Stock, Jeffry B.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
C3 Iwate University; Rohto Pharmaceutical Co Ltd; Princeton University
RP Tomita, H (通讯作者)，Iwate Univ, Lab Visual Neurosci, Grad Course Biol Sci, Div Sci & Engn, 4-3-5 Ueda, Morioka, Iwate 0208551, Japan.
EM htomita@iwate-u.ac.jp
RI ; Tomita, Hiroshi/O-2135-2018
OI Perez, Edwardo/0000-0002-7112-6896; Tomita, Hiroshi/0000-0003-1051-2301;
   Ozaki, Taku/0000-0001-8183-5453
FU Ministry of Education, Culture, Sports, Science and Technology, Japan
   [21K18278, 19H03807, 19K09945, 21K09713]
FX This research was funded by Grants-in-Aid for Scientific Research from
   the Ministry of Education, Culture, Sports, Science and Technology,
   Japan (grant nos. 21K18278, 19H03807, 19K09945, and 21K09713).
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NR 48
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 AUG
PY 2022
VL 23
IS 15
AR 8802
DI 10.3390/ijms23158802
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 3R7BJ
UT WOS:000839063100001
PM 35955937
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Muangnoi, C
   Phumsuay, R
   Jongjitphisut, N
   Waikasikorn, P
   Sangsawat, M
   Rashatasakhon, P
   Paraoan, L
   Rojsitthisak, P
AF Muangnoi, Chawanphat
   Phumsuay, Rianthong
   Jongjitphisut, Nattapong
   Waikasikorn, Pasin
   Sangsawat, Monsin
   Rashatasakhon, Paitoon
   Paraoan, Luminita
   Rojsitthisak, Pornchai
TI Protective Effects of a Lutein Ester Prodrug, Lutein Diglutaric Acid,
   against H2O2-Induced Oxidative Stress in Human Retinal Pigment
   Epithelial Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration; human retinal pigmented epithelium;
   oxidative stress; lutein; lutein diglutaric acid
ID MACULAR DEGENERATION AMD; CURCUMIN DIETHYL DISUCCINATE; INDUCED
   APOPTOSIS; ANTIOXIDANT ENZYMES; SIGNALING PATHWAY; INCLUSION-BODIES; ERK
   ACTIVATION; ARPE-19 CELLS; CANCER CELLS; PATHOGENESIS
AB Oxidative stress-induced cell damage and death of the retinal pigmented epithelium (RPE), a polarized monolayer that maintains retinal health and homeostasis, lead to the development of age-related macular degeneration (AMD). Several studies show that the naturally occurring antioxidant Lutein (Lut) can protect RPE cells from oxidative stress. However, the poor solubility and low oral bioavailability limit the potential of Lut as a therapeutic agent. In this study, lutein diglutaric acid (Lut-DG), a prodrug of Lut, was synthesized and its ability to protect human ARPE-19 cells from oxidative stress was tested compared to Lut. Both Lut and Lut-DG significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Moreover, the immunoblotting analysis indicated that both drugs exerted their protective effects by modulating phosphorylated MAPKs (p38, ERK1/2 and SAPK/JNK) and downstream molecules Bax, Bcl-2 and Cytochrome c. In addition, the enzymatic antioxidants glutathione peroxidase (GPx) and catalase (CAT) and non-enzymatic antioxidant glutathione (GSH) were enhanced in cells treated with Lut and Lut-DG. In all cases, Lut-DG was more effective than its parent drug against oxidative stress-induced damage to RPE cells. These findings highlight Lut-DG as a more potent compound than Lut with the protective effects against oxidative stress in RPE cells through the modulation of key MAPKs, apoptotic and antioxidant molecular pathways.
C1 [Muangnoi, Chawanphat; Phumsuay, Rianthong] Mahidol Univ, Inst Nutr, Cell & Anim Model Unit, Phutthamonthon Dist 73170, Nakhon Pathom, Thailand.
   [Phumsuay, Rianthong; Jongjitphisut, Nattapong; Waikasikorn, Pasin; Sangsawat, Monsin; Rojsitthisak, Pornchai] Chulalongkorn Univ, Fac Pharmaceut Sci, Nat Prod Ageing & Chron Dis Res Unit, Bangkok 10330, Thailand.
   [Jongjitphisut, Nattapong] Chulalongkorn Univ, Fac Pharmaceut Sci, Pharmaceut Sci & Technol Program, Bangkok 10330, Thailand.
   [Rashatasakhon, Paitoon] Chulalongkorn Univ, Fac Sci, Dept Chem, Bangkok 10330, Thailand.
   [Paraoan, Luminita] Univ Liverpool, Inst Life Course & Med Sci, Dept Eye & Vis Sci, Liverpool L7 8TX, Merseyside, England.
   [Rojsitthisak, Pornchai] Chulalongkorn Univ, Fac Pharmaceut Sci, Dept Food & Pharmaceut Chem, Bangkok 10330, Thailand.
C3 Mahidol University; Chulalongkorn University; Chulalongkorn University;
   Chulalongkorn University; University of Liverpool; Chulalongkorn
   University
RP Rojsitthisak, P (通讯作者)，Chulalongkorn Univ, Fac Pharmaceut Sci, Nat Prod Ageing & Chron Dis Res Unit, Bangkok 10330, Thailand.; Rojsitthisak, P (通讯作者)，Chulalongkorn Univ, Fac Pharmaceut Sci, Dept Food & Pharmaceut Chem, Bangkok 10330, Thailand.
EM chawanphat.mua@mahidol.ac.th; Rianthong_p@hotmail.com;
   nattapong.pharmcu@gmail.com; stamppasin@gmail.com;
   jansee_93@hotmail.com; paitoon.r@chula.ac.th;
   Luminita.Paraoan@liverpool.ac.uk; pornchai.r@chula.ac.th
RI Paraoan, Luminita/K-1066-2016
OI Paraoan, Luminita/0000-0001-7568-7116; Muangnoi,
   Chawanphat/0000-0002-5422-1023
FU National Research Council of Thailand [IRN FY2020 507/2563]; Thailand
   Science Research and Innovation (TSRI) Fund [CU_FRB640001_01_33_3];
   Ratchadaphiseksomphot Endowment Fund for the Natural Products for Ageing
   and Chronic Diseases, Chulalongkorn University
FX This study was supported by Ratchadaphiseksomphot Endowment Fund for the
   Natural Products for Ageing and Chronic Diseases, Chulalongkorn
   University (P.R.). The authors express gratitude to the National
   Research Council of Thailand (IRN FY2020 507/2563) (P.R.) and the
   Thailand Science Research and Innovation (TSRI) Fund
   (CU_FRB640001_01_33_3) (P.R.).
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NR 72
TC 8
Z9 9
U1 4
U2 10
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 MAY
PY 2021
VL 22
IS 9
AR 4722
DI 10.3390/ijms22094722
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA SC0KG
UT WOS:000650371200001
PM 33946898
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Dere, E
   Crowell, S
   Maia, M
   Schuetz, C
   Lai, P
   Bantseev, V
   Booler, H
AF Dere, Edward
   Crowell, Susan
   Maia, Mauricio
   Schuetz, Chris
   Lai, Phillip
   Bantseev, Vladimir
   Booler, Helen
TI Nonclinical Safety Assessment of FHTR2163, An Antigen-Binding Fragment
   Against HTRA1 for the Treatment of Geographic Atrophy
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE drug development; preclinical safety assessment; risk management; safety
   assessment
AB FHTR2163 is an antigen-binding fragment of a humanized immunoglobulin G1 monoclonal antibody directed against high-temperature requirement A serine peptidase 1 (HTRA1) that is being developed as a potential intravitreal (ITV) treatment for patients with geographic atrophy (GA), an advanced form of dry age-related macular degeneration. The nonclinical toxicology program was designed to assess the safety and tolerability of HTRA1 inhibition following ITV administration of FHTR2163 to support ITV administration in patients with GA. FHTR2163 was well tolerated in a single-dose ITV-administered 8-day toxicity study in cynomolgus monkeys following a 50 mu L high (>700 mOsm/kg) osmolality formulation up to 12.5 mg/eye; however, 100 mu L (2x 50 mu L injections) of a high-osmolality formulation resulted in transient retinal detachment. Repeat-dose ITV administration every 2 weeks of FHTR2163 was well tolerated in 8- and 26-week studies with ITV injection of 100 mu L (2x 50 mu L) of iso-osmolar formulation up to 15 mg/eye, or 50 mu L of the high-osmolality formulation up to 12.5 mg/eye. Observed transient and reversible ocular effects included inflammation and perivascular infiltrates, consistent with an immune response attributed to the administration of heterologous (humanized) protein. Overall, FHTR2163 was well tolerated, and the nonclinical package supported the continued clinical development of FHTR2163 in patients with GA.
C1 [Dere, Edward; Schuetz, Chris; Bantseev, Vladimir; Booler, Helen] Genentech Inc, Dept Safety Assessment, 1 DNA Way, San Francisco, CA 94080 USA.
   [Crowell, Susan] Genentech Inc, Dept Preclin & Translat Pharmacokinet & Pharmacod, San Francisco, CA 94080 USA.
   [Maia, Mauricio] Genentech Inc, Dept Bioanalyt Sci, San Francisco, CA 94080 USA.
   [Lai, Phillip] Genentech Inc, Dept Early Clin Dev OMNI, San Francisco, CA 94080 USA.
   [Booler, Helen] F Hoffmann La Roche Ltd, Dept BIOm & Pathol, Basel, Switzerland.
C3 Roche Holding; Genentech; Roche Holding; Genentech; Roche Holding;
   Genentech; Roche Holding; Genentech; Roche Holding
RP Dere, E (通讯作者)，Genentech Inc, Dept Safety Assessment, 1 DNA Way, San Francisco, CA 94080 USA.
EM dere.edward@gene.com
OI Dere, Edward/0000-0002-8233-9774
CR [Anonymous], 1997, S6R1 ICH
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NR 48
TC 1
Z9 1
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD APR
PY 2021
VL 49
IS 3
SI SI
BP 610
EP 620
DI 10.1177/0192623320976095
PG 11
WC Pathology; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology; Toxicology
GA QZ1JO
UT WOS:000630491300019
PM 33297886
DA 2022-11-30
ER

PT J
AU Hemalakshmi, GR
   Santhi, D
   Mani, VRS
   Geetha, A
   Prakash, NB
AF Hemalakshmi, G. R.
   Santhi, D.
   Mani, V. R. S.
   Geetha, A.
   Prakash, N. B.
TI Classification of retinal fundus image using MS-DRLBP features and
   CNN-RBF classifier
SO JOURNAL OF AMBIENT INTELLIGENCE AND HUMANIZED COMPUTING
LA English
DT Article
DE Diabetic retinopathy (DR); Age-related macular degeneration (AMD);
   Retinal fundus images; Multi-scale discriminative robust LBP (MS-DRLBP);
   Convolution neural network (CNN); Radial basis function (RBF)
ID RADIAL BASIS FUNCTION; MACULAR DEGENERATION; GRAY-SCALE; SEGMENTATION;
   DIAGNOSIS; PATTERNS; NETWORK; INDEX
AB The most common retinal diseases that are to be diagnosed are Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD) and Choroidal Neovascularization (CNV). For the people above 60 years of age, detection of these retinal diseases is an important task for treatment that reduces the risk of vision loss. Retinal fundus images play a significant role in the detection of DR, AMD and CNV disease diagnosis and treatment. The existing techniques for the detection of DR, AMD and CNV have not fulfilled with the classification accuracy of the retinal diseases effectively. This research work proposes an efficient classification framework for retinal fundus image recognition to overcome these drawbacks. Initially, the input image from the publicly available STARE database is preprocessed with the following three steps (a) Specular reflection removal and smoothing, (b) contrast enhancement and (c) retinal region expansion. With the preprocessed image, the features are extracted using Multi-Scale Discriminative Robust Local Binary Pattern (MS-DRLBP), based on RGB component selection, Gradient operation, and LBP descriptor. Finally, classification was done using hybrid Convolution Neural Network (CNN) and Radial Basis Function (RBF) model (CNN-RBF) which classifies the retinal fundus images into four classes such as DR, AMD, CNV and Normal (NR). Experimental results of the proposed method gives an accuracy of 97.22% compared with the existing other methodologies.
C1 [Hemalakshmi, G. R.; Santhi, D.; Mani, V. R. S.; Geetha, A.; Prakash, N. B.] Natl Engn Coll, Kovilpatti, Tamil Nadu, India.
C3 National Engineering College - India
RP Hemalakshmi, GR (通讯作者)，Natl Engn Coll, Kovilpatti, Tamil Nadu, India.
EM grhemalakshmi@gmail.com
RI NB, Prakash/G-3995-2018; G.R, Hemalakshmi/AAO-6763-2021; Santhi,
   D/AAC-5211-2022
OI NB, Prakash/0000-0002-9663-7625; G.R, Hemalakshmi/0000-0002-3261-8820; 
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U1 0
U2 9
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1868-5137
EI 1868-5145
J9 J AMB INTEL HUM COMP
JI J. Ambient Intell. Humaniz. Comput.
PD SEP
PY 2021
VL 12
IS 9
BP 8747
EP 8762
DI 10.1007/s12652-020-02647-y
EA NOV 2020
PG 16
WC Computer Science, Artificial Intelligence; Computer Science, Information
   Systems; Telecommunications
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Telecommunications
GA TT8HC
UT WOS:000587274600002
DA 2022-11-30
ER

PT J
AU Samson, FP
   He, WL
   Sripathi, SR
   Patrick, AT
   Madu, J
   Chung, H
   Frost, MC
   Jee, D
   Gutsaeva, DR
   Jahng, WJ
AF Samson, Faith Pwaniyibo
   He, Weilue
   Sripathi, Srinivas R.
   Patrick, Ambrose Teru
   Madu, Joshua
   Chung, Hyewon
   Frost, Megan C.
   Jee, Donghyun
   Gutsaeva, Diana R.
   Jahng, Wan Jin
TI Dual Switch Mechanism of Erythropoietin as an Antiapoptotic and
   Pro-Angiogenic Determinant in the Retina
SO ACS OMEGA
LA English
DT Article
ID GROWTH-FACTOR SECRETION; NITRIC-OXIDE; PIGMENT EPITHELIUM; OXIDATIVE
   STRESS; ENDOTHELIAL-CELLS; RAT MODEL; IN-VITRO; RECEPTOR; EXPRESSION;
   NEUROPROTECTION
AB Constant or intense light degenerates the retina and retinal pigment epithelial cells. Light generates reactive oxygen species and nitric oxide leading to initial reactions of retinal degeneration. Apoptosis is the primary mechanism of abnormal death of photoreceptors, retinal ganglion cells, or retinal pigment epithelium (RPE) in degenerative retinal diseases, including diabetic retinopathy and age-related macular degeneration. The current study evaluated the function of erythropoietin (EPO) on angiogenesis and apoptosis in the retina and RPE under oxidative stress. We determined the pro-angiogenic and antiapoptotic mechanism of EPO under stress conditions using a conditional EPO knockdown model using siRNA, EPO addition, proteomics, immunocytochemistry, and bioinformatic analysis. Our studies verified that EPO protected retinal cells from light-, hypoxia-, hyperoxia-, and hydrogen peroxide-induced apoptosis through caspase inhibition, whereas up-regulated angiogenic reactions through vascular endothelial growth factor (VEGF) and angiotensin pathway. We demonstrated that the EPO expression in the retina and subsequent serine/threonine/tyrosine kinase phosphorylations might be linked to oxidative stress response tightly to determining angiogenesis and apoptosis. Neuroprotective roles of EPO may involve the balance between antiapoptotic and proangiogenic signaling molecules, including BCL-xL, c-FOS, caspase-3, nitric oxide, angiotensin, and VEGF receptor. Our data indicate a new therapeutic application of EPO toward retinal degeneration based on the dual roles in apoptosis and angiogenesis at the molecular level under oxidative stress.
C1 [Samson, Faith Pwaniyibo; Patrick, Ambrose Teru; Madu, Joshua; Jahng, Wan Jin] Amer Univ Nigeria, Dept Petr Chem, Yola 640101, Nigeria.
   [He, Weilue; Frost, Megan C.] Michigan Technol Univ, Dept Biomed Engn, Houghton, MI 49931 USA.
   [Sripathi, Srinivas R.] Johns Hopkins Univ, Wilmer Eye Inst, Dept Ophthalmol, Sch Med, Baltimore, MD 21205 USA.
   [Chung, Hyewon] Konkuk Univ, Sch Med, Dept Ophthalmol, Seoul 05030, South Korea.
   [Jee, Donghyun] Catholic Univ Korea, Div Vitreous & Retina, Dept Ophthalmol, St Vincents Hosp,Coll Med, Suwon 16247, South Korea.
   [Gutsaeva, Diana R.] Augusta Univ, Dept Ophthalmol, Augusta, GA 30912 USA.
C3 American University of Nigeria; Michigan Technological University; Johns
   Hopkins University; Johns Hopkins Medicine; Konkuk University; Konkuk
   University Medical Center; 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 Research Assistantship and Teaching Assistantship from the American
   University of Nigeria
FX The current research was supported in part by Research Assistantship and
   Teaching Assistantship from the American University of Nigeria.
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NR 117
TC 11
Z9 11
U1 0
U2 7
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 AUG 25
PY 2020
VL 5
IS 33
BP 21113
EP 21126
DI 10.1021/acsomega.0c02763
PG 14
WC Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry
GA NJ9DP
UT WOS:000566344600046
PM 32875248
OA Green Published
DA 2022-11-30
ER

PT J
AU Sun, YX
   Wang, X
   Shang, JL
   Liu, JX
   Zheng, CH
   Lei, XJ
AF Sun, Yingxia
   Wang, Xuan
   Shang, Junliang
   Liu, Jin-Xing
   Zheng, Chun-Hou
   Lei, Xiujuan
TI Introducing Heuristic Information Into Ant Colony Optimization Algorithm
   for Identifying Epistasis
SO IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
LA English
DT Article
DE Ant colony optimization; epistasis; expert knowledge; genome-wide
   association studies; gini index; mutual information
ID MUTUAL INFORMATION; INFERENCE
AB Epistasis learning, which is aimed at detecting associations between multiple Single Nucleotide Polymorphisms (SNPs) and complex diseases, has gained increasing attention in genome wide association studies. Although much work has been done on mapping the SNPs underlying complex diseases, there is still difficulty in detecting epistatic interactions due to the lack of heuristic information to expedite the search process. In this study, a method EACO is proposed to detect epistatic interactions based on the ant colony optimization (ACO) algorithm, the highlights of which are the introduced heuristic information, fitness function, and a candidate solutions filtration strategy. The heuristic information multi-SURF* is introduced into EACO for identifying epistasis, which is incorporated into ant-decision rules to guide the search with linear time. Two functionally complementary fitness functions, mutual information and the Gini index, are combined to effectively evaluate the associations between SNP combinations and the phenotype. Furthermore, a strategy for candidate solutions filtration is provided to adaptively retain all optimal solutions which yields a more accurate way for epistasis searching. Experiments of EACO, as well as three ACO based methods (AntEpiSeeker, MACOED, and epiACO) and four commonly used methods (BOOST, SNPRuler, TEAM, and epiMODE) are performed on both simulation data sets and a real data set of age-related macular degeneration. Results indicate that EACO is promising in identifying epistasis.
C1 [Sun, Yingxia; Wang, Xuan; Shang, Junliang; Liu, Jin-Xing] Qufu Normal Univ, Sch Informat Sci & Engn, Rizhao 276826, Peoples R China.
   [Zheng, Chun-Hou] Qufu Normal Univ, Sch Software Engn, Rizhao 276826, Peoples R China.
   [Lei, Xiujuan] Shannxi Normal Univ, Sch Comp Sci, Xian 710062, Peoples R China.
C3 Qufu Normal University; Qufu Normal University; Shaanxi Normal
   University
RP Shang, JL; Liu, JX (通讯作者)，Qufu Normal Univ, Sch Informat Sci & Engn, Rizhao 276826, Peoples R China.
EM sunyingxia026@163.com; wangxuanfine@163.com; shangjunliang110@163.com;
   sdcavell@126.com; zhengch99@126.com; xjlei@snnu.edu.cn
FU National Science Foundation of China [61502272, 61572284, 61701279,
   61702299]; Shandong Provincial Natural Science Foundation [ZR2017PF006,
   ZR2018MA019]; Project of Shandong Province Higher Educational Science
   and Technology Program [J18KA373, J17KA063]
FX This work was supported by the National Science Foundation of China
   (61502272, 61572284, 61701279, 61702299), the Shandong Provincial
   Natural Science Foundation (ZR2017PF006, ZR2018MA019), and the Project
   of Shandong Province Higher Educational Science and Technology Program
   (J18KA373, J17KA063).
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NR 46
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U1 0
U2 15
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 1545-5963
EI 1557-9964
J9 IEEE ACM T COMPUT BI
JI IEEE-ACM Trans. Comput. Biol. Bioinform.
PD JUL-AUG
PY 2020
VL 17
IS 4
BP 1253
EP 1261
DI 10.1109/TCBB.2018.2879673
PG 9
WC Biochemical Research Methods; Computer Science, Interdisciplinary
   Applications; Mathematics, Interdisciplinary Applications; Statistics &
   Probability
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Computer Science; Mathematics
GA MW1AD
UT WOS:000556777900015
PM 30403637
DA 2022-11-30
ER

PT J
AU Enayati, S
   Chang, KR
   Achour, H
   Cho, KS
   Xu, FY
   Guo, S
   Enayati, KZ
   Xie, J
   Zhao, E
   Turunen, T
   Sehic, A
   Lu, L
   Utheim, TP
   Chen, DF
AF Enayati, Sam
   Chang, Karen
   Achour, Hamida
   Cho, Kin-Sang
   Xu, Fuyi
   Guo, Shuai
   Enayati, Katarina Z.
   Xie, Jia
   Zhao, Eric
   Turunen, Tytteli
   Sehic, Amer
   Lu, Lu
   Utheim, Tor Paaske
   Chen, Dong Feng
TI Electrical Stimulation Induces Retinal Muller Cell Proliferation and
   Their Progenitor Cell Potential
SO CELLS
LA English
DT Article
DE electrical-stimulation; retina; glial cells; Muller cells;
   proliferation; retinitis pigmentosa
ID GANGLION-CELLS; PROMOTES; SURVIVAL; PHOTORECEPTORS; ACTIVATION; NEURON;
   GLIA; DRY
AB Non-invasive electrical stimulation (ES) is increasingly applied to improve vision in untreatable eye conditions, such as retinitis pigmentosa and age-related macular degeneration. Our previous study suggested that ES promoted retinal function and the proliferation of progenitor-like glial cells in mice with inherited photoreceptor degeneration; however, the underlying mechanism remains obscure. Muller cells (MCs) are thought to be dormant residential progenitor cells that possess a high potential for retinal neuron repair and functional plasticity. Here, we showed that ES with a ramp waveform of 20 Hz and 300 mu A of current was effective at inducing mouse MC proliferation and enhancing their expression of progenitor cell markers, such as Crx (cone-rod homeobox) and Wnt7, as well as their production of trophic factors, including ciliary neurotrophic factor. RNA sequencing revealed that calcium signaling pathway activation was a key event, with a false discovery rate of 5.33 x 10(-8) (p = 1.78 x 10(-10)) in ES-mediated gene profiling changes. Moreover, the calcium channel blocker, nifedipine, abolished the observed effects of ES on MC proliferation and progenitor cell gene induction, supporting a central role of ES-induced Ca2+ signaling in the MC changes. Our results suggest that low-current ES may present a convenient tool for manipulating MC behavior toward neuroregeneration and repair.
C1 [Enayati, Sam; Chang, Karen; Achour, Hamida; Cho, Kin-Sang; Guo, Shuai; Enayati, Katarina Z.; Xie, Jia; Zhao, Eric; Turunen, Tytteli; Utheim, Tor Paaske; Chen, Dong Feng] Harvard Med Sch, Schepens Eye Res Inst, Dept Ophthalmol, Massachusetts Eye & Ear, Boston, MA 02114 USA.
   [Enayati, Sam; Utheim, Tor Paaske] Oslo Univ Hosp, Dept Med Biochem, N-0372 Oslo, Norway.
   [Enayati, Sam; Utheim, Tor Paaske] Vestre Viken Hosp Trust, Drammen Hosp, Dept Ophthalmol, N-3004 Drammen, Norway.
   [Enayati, Sam; Achour, Hamida] Univ Oslo, Inst Clin Med, N-0318 Oslo, Norway.
   [Xu, Fuyi; Lu, Lu] Univ Tennessee, Dept Genet Genom & Informat, Hlth Sci Ctr, Memphis, TN 38163 USA.
   [Sehic, Amer; Utheim, Tor Paaske] Univ Oslo, Dept Oral Biol, N-0372 Oslo, Norway.
   [Sehic, Amer; Utheim, Tor Paaske] Univ Oslo, Fac Dent, N-0372 Oslo, Norway.
   [Utheim, Tor Paaske] Oslo Univ Hosp, Dept Plast & Reconstruct Surg, N-0027 Oslo, Norway.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Schepens Eye Research Institute; University of Oslo;
   University of Oslo; University of Tennessee System; University of
   Tennessee Health Science Center; University of Oslo; University of Oslo;
   University of Oslo
RP Chen, DF (通讯作者)，Harvard Med Sch, Schepens Eye Res Inst, Dept Ophthalmol, Massachusetts Eye & Ear, Boston, MA 02114 USA.
EM samenayati@gmail.com; karen_chang@meei.harvard.edu;
   ach.hamida@gmail.com; kinsang_cho@meei.harvard.edu; fxu10@uthsc.edu;
   james.shuaig@gmail.com; k.zihlavnikova@gmail.com; x.jessica@outlook.com;
   eric_zhao@brown.edu; tutteli_turunen@meei.harvard.edu;
   amer.sehic@odont.uio.no; llu@uthsc.edu; utheim2@gmail.com;
   dongfeng_chen@meei.harvard.edu
RI Chen, Dong/AAJ-2444-2020; Chang, Karen/AAE-8296-2022
OI Chen, Dong/0000-0001-6283-8843; Cho, Kin-Sang/0000-0003-4285-615X;
   Chang, Karen/0000-0002-5920-6201; Zhao, Eric/0000-0002-1314-0518
FU National Institutes of Health/National Eye Institute [EY025913,
   EY025259, P30EY003790, EY023651, NS099700]; South-Eastern Norway
   Regional Health Authority; Norwegian Association of the Blind and
   Partially Sighted; Massachusetts Lions Foundation
FX This work was supported by grants from the National Institutes of
   Health/National Eye Institute (EY025913, EY025259, P30EY003790,
   EY023651, NS099700), the South-Eastern Norway Regional Health Authority,
   Massachusetts Lions Foundation, and Norwegian Association of the Blind
   and Partially Sighted.
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NR 57
TC 10
Z9 10
U1 2
U2 3
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD MAR
PY 2020
VL 9
IS 3
AR 781
DI 10.3390/cells9030781
PG 18
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA LI2TV
UT WOS:000529337400258
PM 32210151
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Jimenez-Garcia, J
   Romero-Oraa, R
   Garcia, M
   Lopez-Galvez, MI
   Hornero, R
AF Jimenez-Garcia, Jorge
   Romero-Oraa, Roberto
   Garcia, Maria
   Lopez-Galvez, Maria I.
   Hornero, Roberto
TI Combination of Global Features for the Automatic Quality Assessment of
   Retinal Images
SO ENTROPY
LA English
DT Article
DE diabetic retinopathy; fundus images; retinal image quality assessment;
   Shannon entropy; spectral entropy; continuous wavelet transform;
   multilayer perceptron
ID DIABETIC-RETINOPATHY; VESSEL SEGMENTATION; FEATURE-SELECTION; WAVELET;
   RELEVANCE; DIAGNOSIS; CLARITY
AB Diabetic retinopathy (DR) is one of the most common causes of visual loss in developed countries. Computer-aided diagnosis systems aimed at detecting DR can reduce the workload of ophthalmologists in screening programs. Nevertheless, a large number of retinal images cannot be analyzed by physicians and automatic methods due to poor quality. Automatic retinal image quality assessment (RIQA) is needed before image analysis. The purpose of this study was to combine novel generic quality features to develop a RIQA method. Several features were calculated from retinal images to achieve this goal. Features derived from the spatial and spectral entropy-based quality (SSEQ) and the natural images quality evaluator (NIQE) methods were extracted. They were combined with novel sharpness and luminosity measures based on the continuous wavelet transform (CWT) and the hue saturation value (HSV) color model, respectively. A subset of non-redundant features was selected using the fast correlation-based filter (FCBF) method. Subsequently, a multilayer perceptron (MLP) neural network was used to obtain the quality of images from the selected features. Classification results achieved 91.46% accuracy, 92.04% sensitivity, and 87.92% specificity. Results suggest that the proposed RIQA method could be applied in a more general computer-aided diagnosis system aimed at detecting a variety of retinal pathologies such as DR and age-related macular degeneration.
C1 [Jimenez-Garcia, Jorge; Romero-Oraa, Roberto; Garcia, Maria; Lopez-Galvez, Maria I.; Hornero, Roberto] Univ Valladolid, Biomed Engn Grp, Paseo Belen 15, E-47011 Valladolid, Spain.
   [Lopez-Galvez, Maria I.] Hosp Clin Univ Valladolid, Dept Ophthalmol, Ave Ramon y Cajal 3, Valladolid 47003, Spain.
   [Lopez-Galvez, Maria I.] Univ Valladolid, Inst Oftalmobiol Aplicada, Paseo Belen 17, E-47011 Valladolid, Spain.
   [Hornero, Roberto] Univ Valladolid, Inst Invest Matemat IMUVA, E-47011 Valladolid, Spain.
   [Hornero, Roberto] Univ Salamanca, Inst Neurociencias Castilla & Leon INCYL, Salamanca 37007, Spain.
C3 Universidad de Valladolid; Universidad de Valladolid; Universidad de
   Valladolid; University of Salamanca
RP Jimenez-Garcia, J (通讯作者)，Univ Valladolid, Biomed Engn Grp, Paseo Belen 15, E-47011 Valladolid, Spain.
EM jorge.jimenez@gib.tel.uva.es; roberto.romero@gib.tel.uva.es;
   maria.garcia@tel.uva.es; maribel@ioba.med.uva.es; robhor@tel.uva.es
RI García, María/F-3347-2011; Hornero, Roberto/M-5313-2019
OI García, María/0000-0002-4037-0351; Hornero, Roberto/0000-0001-9915-2570;
   Romero-Oraa, Roberto/0000-0003-2996-4754; Jimenez-Garcia,
   Jorge/0000-0001-5540-6778
FU Ministerio de Ciencia, Innovacion y Universidades; 'European Regional
   Development Fund' (FEDER) [RTC-2015-3467-1, DPI2017-84280-R]; European
   Commission; FEDER under project 'Analisis y correlacion entre el genoma
   completo y la actividad cerebral para la ayuda en el diagnostico de la
   enfermedad de Alzheimer' ('Cooperation Programme Interreg V-A
   Spain-Portugal POCTEP 2014-2020'); 'Ayudas para la contratacion de
   personal tecnico de apoyo a la investigacion' grant from the 'Junta de
   Castilla y Leon' - European Social Fund; Youth Employment Initiative;
   Junta de Castilla y Leon - European Social Fund
FX This research was supported by 'Ministerio de Ciencia, Innovacion y
   Universidades' and 'European Regional Development Fund' (FEDER) under
   projects RTC-2015-3467-1 and DPI2017-84280-R, and by 'European
   Commission' and FEDER under project 'Analisis y correlacion entre el
   genoma completo y la actividad cerebral para la ayuda en el diagnostico
   de la enfermedad de Alzheimer' ('Cooperation Programme Interreg V-A
   Spain-Portugal POCTEP 2014-2020'). J.J.-G. was in receipt of a 'Ayudas
   para la contratacion de personal tecnico de apoyo a la investigacion'
   grant from the 'Junta de Castilla y Leon' funded by the European Social
   Fund and Youth Employment Initiative. R.R.-O. was in receipt of a
   predoctoral scholarshipfrom the 'Junta de Castilla y Leon' funded by the
   European Social Fund. The APC was funded by the 36th Annual Conference
   of the Spanish Society of Biomedical Engineering organization and
   Entropy Journal.
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NR 63
TC 4
Z9 4
U1 2
U2 6
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1099-4300
J9 ENTROPY-SWITZ
JI Entropy
PD MAR 21
PY 2019
VL 21
IS 3
AR 311
DI 10.3390/e21030311
PG 19
WC Physics, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Physics
GA HT2JG
UT WOS:000464388400009
PM 33267025
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Hayashi, H
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AF Hayashi, Hisaki
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   Yamamura, Aya
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   Nakahara, Tsutomu
   Kamei, Motohiro
   Sato, Motohiko
TI Activator of G-protein signaling 8 is involved in VEGF-induced choroidal
   neovascularization
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RECEPTOR-INDEPENDENT ACTIVATOR; MACULAR DEGENERATION; IDENTIFICATION;
   MECHANISMS; THERAPY
AB Choroidal neovascularization (CNV) is associated with age-related macular degeneration (AMD), a major cause of vision loss among elderly people. Vascular endothelial cell growth factor (VEGF) is essential for the development and progression of AMD, and VEGF signaling molecules are effective targets for the treatment of AMD. We recently reported that activator of G-protein signaling 8 (AGS8), a receptor-independent G beta gamma regulator, is involved in VEGF-induced angiogenesis in cultured endothelial cells (EC); however, the role of AGS8 in CNV is not yet understood. This study aimed to explore the role of AGS8 in CNV in cultured cells, explanted choroid tissue, and laser-induced CNV in a mouse AMD model. AGS8 knockdown in cultured choroidal EC inhibited VEGF-induced VEGFR-2 phosphorylation, cell proliferation, and migration. AGS8 knockdown also downregulated cell sprouting from mouse choroidal tissue in ex vivo culture. A mouse model of laser-induced CNV, created to analyze the roles of AGS8 in vivo, demonstrated that AGS8 mRNA was significantly upregulated in choroidal lesions and AGS8 was specifically expressed in the neovasculature. Local AGS8 knockdown in intravitreal tissue significantly inhibited laser-induced AGS8 upregulation and suppressed CNV, suggesting that AGS8 knockdown in the choroid has therapeutic potential for AMD. Together, these results demonstrate that AGS8 plays critical roles in VEGF-induced CNV.
C1 [Hayashi, Hisaki; Al Mamun, Abdullah; Yamamura, Aya; Sato, Motohiko] Aichi Med Univ, Dept Physiol, Nagakute, Aichi, Japan.
   [Takeyama, Masayuki; Kamei, Motohiro] Aichi Med Univ, Dept Ophthalmol, Nagakute, Aichi, Japan.
   [Zako, Masahiro] Asai Hosp, Dept Ophthalmol, Seto, Japan.
   [Yagasaki, Rina; Nakahara, Tsutomu] Kitasato Univ, Dept Mol Pharmacol, Sch Pharm, Tokyo, Japan.
C3 Aichi Medical University; Aichi Medical University; Kitasato University
RP Hayashi, H; Sato, M (通讯作者)，Aichi Med Univ, Dept Physiol, Nagakute, Aichi, Japan.
EM h-hayashi@aichi-med-u.ac.jp; motosato@aichi-med-u.ac.jp
OI Al Mamun, Md. Abdullah/0000-0003-3839-9603
FU JPSP [16K08600, 16K08508]
FX We thank Ms. Rie Takahashi for technical assistance. This work was
   supported by a JPSP Grant-in-Aid for HH (16K08600) and for MS
   (16K08508).
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NR 37
TC 2
Z9 2
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 FEB 7
PY 2019
VL 9
AR 1560
DI 10.1038/s41598-018-38067-4
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HK5PC
UT WOS:000458017800028
PM 30733465
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zhao, J
   Wang, YX
   Zhang, Q
   Wei, WB
   Xu, L
   Jonas, JB
AF Zhao, Jing
   Wang, Ya Xing
   Zhang, Qi
   Wei, Wen Bin
   Xu, Liang
   Jonas, Jost B.
TI Macular Choroidal Small-Vessel Layer, Sattler's Layer and Haller's Layer
   Thicknesses: The Beijing Eye Study
SO SCIENTIFIC REPORTS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; ANGLE-CLOSURE; VISUAL-ACUITY;
   DIABETIC-RETINOPATHY; HEALTHY-SUBJECTS; DEGENERATION; VASCULATURE;
   SECONDARY
AB To study macular choroidal layer thickness, 3187 study participants from the population-based Beijing Eye Study underwent spectral-domain optical coherence tomography with enhanced depth imaging for thickness measurements of the macular small-vessel layer, including the choriocapillaris, medium-sized choroidal vessel layer (Sattler's layer) and large choroidal vessel layer (Haller's layer). In multivariate analysis, greater thickness of all three choroidal layers was associated (all P < 0.05) with higher prevalence of age-related macular degeneration (AMD) (except for geographic atrophy), while it was not significantly (all P > 0.05) associated with the prevalence of open-angle glaucoma or diabetic retinopathy. There was a tendency (0.07 > P > 0.02) toward thinner choroidal layers in chronic angle-closure glaucoma. The ratio of small-vessel layer thickness to total choroidal thickness increased (P < 0.001; multivariate analysis) with older age and longer axial length, while the ratios of Sattler's layer and Haller's layer thickness to total choroidal thickness decreased. A higher ratio of small-vessel layer thickness to total choroidal thickness was significantly associated with a lower prevalence of AMD (early type, intermediate type, late geographic type). Axial elongation-associated and aging-associated choroidal thinning affected Haller's and Sattler's layers more markedly than the small-vessel layer. Non-exudative and exudative AMD, except for geographic atrophy, was associated with slightly increased choroidal thickness.
C1 [Zhao, Jing; Wang, Ya Xing; Zhang, Qi; Xu, Liang; Jonas, Jost B.] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Inst Ophthalmol, Beijing, Peoples R China.
   [Zhao, Jing; Wang, Ya Xing; Zhang, Qi; Xu, Liang; Jonas, Jost B.] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Ophthalmol & Visual Sci Key Lab, Beijing, Peoples R China.
   [Wei, Wen Bin] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing, Peoples R China.
   [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Heidelberg, Germany.
C3 Capital Medical University; Capital Medical University; Capital Medical
   University; Ruprecht Karls University Heidelberg
RP Wang, YX; Xu, L (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Inst Ophthalmol, Beijing, Peoples R China.; Wang, YX; Xu, L (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Ophthalmol & Visual Sci Key Lab, Beijing, Peoples R China.; Wei, WB (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing, Peoples R China.
EM yaxingw@gmail.com; tr_weiwenbin@163.com; xlbio1@163.com
RI wang, YA XING/K-9671-2016
OI wang, YA XING/0000-0003-2749-7793; Jonas, Jost/0000-0003-2972-5227
FU National Natural Science Foundation of China [81770890]
FX Supported by National Natural Science Foundation of China (grant #
   81770890)
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NR 41
TC 35
Z9 36
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAR 13
PY 2018
VL 8
AR 4411
DI 10.1038/s41598-018-22745-4
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FZ0EZ
UT WOS:000427241500012
PM 29535365
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU MacDonald, DA
   Martin, J
   Muthusamy, KK
   Luo, JK
   Pyles, E
   Rafique, A
   Huang, T
   Potocky, T
   Liu, Y
   Cao, JT
   Bono, F
   Delesque, N
   Savi, P
   Francis, J
   Amirkhosravi, A
   Meyer, T
   Romano, C
   Glinka, M
   Yancopoulos, GD
   Stahl, N
   Wiegand, SJ
   Papadopoulos, N
AF MacDonald, Douglas A.
   Martin, Joel
   Muthusamy, Kathir K.
   Luo, Jiann-Kae
   Pyles, Erica
   Rafique, Ashique
   Huang, Tammy
   Potocky, Terra
   Liu, Yang
   Cao, Jingtai
   Bono, Francoise
   Delesque, Nathalie
   Savi, Pierre
   Francis, John
   Amirkhosravi, Ali
   Meyer, Todd
   Romano, Carmelo
   Glinka, Meredith
   Yancopoulos, George D.
   Stahl, Neil
   Wiegand, Stanley J.
   Papadopoulos, Nicholas
TI Aflibercept exhibits VEGF binding stoichiometry distinct from
   bevacizumab and does not support formation of immune-like complexes
SO ANGIOGENESIS
LA English
DT Article
DE VEGF; Bevacizumab; Aflibercept; Immune complexes
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; RANIBIZUMAB; TRAP;
   ANGIOGENESIS; RECEPTORS; INJECTION; ANTIBODY; AFFINITY; THERAPY
AB Anti-vascular endothelial growth factor (VEGF) therapies have improved clinical outcomes for patients with cancers and retinal vascular diseases. Three anti-VEGF agents, pegaptanib, ranibizumab, and aflibercept, are approved for ophthalmic indications, while bevacizumab is approved to treat colorectal, lung, and renal cancers, but is also used off-label to treat ocular vascular diseases. The efficacy of bevacizumab relative to ranibizumab in treating neovascular age-related macular degeneration has been assessed in several trials. However, questions persist regarding its safety, as bevacizumab can form large complexes with dimeric VEGF(165), resulting in multimerization of the Fc domain and platelet activation. Here, we compare binding stoichiometry, Fc gamma receptor affinity, platelet activation, and binding to epithelial and endothelial cells in vitro for bevacizumab and aflibercept, in the absence or presence of VEGF. In contrast to bevacizumab, aflibercept forms a homogenous 1:1 complex with each VEGF dimer. Unlike multimeric bevacizumab:VEGF complexes, the monomeric aflibercept:VEGF complex does not exhibit increased affinity for low-affinity Fc gamma receptors, does not activate platelets, nor does it bind to the surface of epithelial or endothelial cells to a greater degree than unbound aflibercept or control Fc. The latter finding reflects the fact that aflibercept binds VEGF in a unique manner, distinct from antibodies not only blocking the amino acids necessary for VEGFR1/R2 binding but also occluding the heparin-binding site on VEGF(165).
C1 [MacDonald, Douglas A.; Martin, Joel; Muthusamy, Kathir K.; Luo, Jiann-Kae; Pyles, Erica; Rafique, Ashique; Huang, Tammy; Potocky, Terra; Liu, Yang; Cao, Jingtai; Romano, Carmelo; Glinka, Meredith; Yancopoulos, George D.; Stahl, Neil; Wiegand, Stanley J.; Papadopoulos, Nicholas] Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
   [Bono, Francoise; Delesque, Nathalie; Savi, Pierre] Sanofi, Toulouse, France.
   [Francis, John; Amirkhosravi, Ali; Meyer, Todd] Florida Hosp, Thrombosis Res Ctr, Orlando, FL USA.
C3 Regeneron; Sanofi-Aventis; Sanofi France; Adventist Health Services;
   AdventHealth
RP Papadopoulos, N (通讯作者)，Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
EM nicholas.papadopoulos@regeneron.com
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NR 41
TC 24
Z9 26
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD JUL
PY 2016
VL 19
IS 3
BP 389
EP 406
DI 10.1007/s10456-016-9515-8
PG 18
WC Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA DQ5BO
UT WOS:000379219600010
PM 27234973
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Niu, SJ
   Chen, Q
   de Sisternes, L
   Rubin, DL
   Zhang, WW
   Liu, QH
AF Niu, Sijie
   Chen, Qiang
   de Sisternes, Luis
   Rubin, Daniel L.
   Zhang, Weiwei
   Liu, Qinghuai
TI Automated retinal layers segmentation in SD-OCT images using
   dual-gradient and spatial correlation smoothness constraint
SO COMPUTERS IN BIOLOGY AND MEDICINE
LA English
DT Article
DE Spectral domain optical coherence tomography; Spatial correlation
   smoothness constraint; Edge flow; Gradient compensation; Automatic
   segmentation
ID OPTICAL COHERENCE TOMOGRAPHY; ACTIVE CONTOUR APPROACH; NERVE HEAD;
   HIGH-SPEED; CLASSIFICATION; DRUSEN; MODEL; MAP
AB Automatic segmentation of retinal layers in spectral domain optical coherence tomography (SD-OCT) images plays a vital role in the quantitative assessment of retinal disease, because it provides detailed information which is hard to process manually. A number of algorithms to automatically segment retinal layers have been developed; however, accurate edge detection is challenging. We developed an automatic algorithm for segmenting retinal layers based on dual-gradient and spatial correlation smoothness constraint. The proposed algorithm utilizes a customized edge flow to produce the edge map and a convolution operator to obtain local gradient map in the axial direction. A valid search region is then defined to identify layer boundaries. Finally, a spatial correlation smoothness constraint is applied to remove anomalous points at the layer boundaries. Our approach was tested on two datasets including 10 cubes from 10 healthy eyes and 15 cubes from 6 patients with age-related macular degeneration. A quantitative evaluation of our method was performed on more than 600 images from cubes obtained in five healthy eyes. Experimental results demonstrated that the proposed method can estimate six layer boundaries accurately. Mean absolute boundary positioning differences and mean absolute thickness differences (mean +/- SD) were 4.43 +/- 3.32 mu m and 0.22 +/- 0.24 mu m, respectively. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Niu, Sijie; Chen, Qiang] Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Nanjing 210094, Jiangsu, Peoples R China.
   [de Sisternes, Luis; Rubin, Daniel L.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA.
   [Zhang, Weiwei; Liu, Qinghuai] Nanjing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Nanjing, Jiangsu, Peoples R China.
C3 Nanjing University of Science & Technology; Stanford University; Nanjing
   Medical University
RP Niu, SJ (通讯作者)，Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Nanjing 210094, Jiangsu, Peoples R China.
EM sjniu@hotmail.com
RI chen, qiang/GWZ-7308-2022
OI Liu, Qinghuai/0000-0003-1605-1964
FU Qing Lan Project; Programme of Introducing Talents of Discipline to
   Universities [B13022]; Fundamental Research Funds for the Central
   Universities [30920140111004]
FX This work was supported by the Qing Lan Project, the Programme of
   Introducing Talents of Discipline to Universities, No. B13022, and the
   Fundamental Research Funds for the Central Universities, No.
   30920140111004.
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NR 50
TC 36
Z9 38
U1 0
U2 13
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 NOV 1
PY 2014
VL 54
BP 116
EP 128
DI 10.1016/j.compbiomed.2014.08.028
PG 13
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 AT8NM
UT WOS:000345189800014
PM 25240102
DA 2022-11-30
ER

PT J
AU Yang, HK
   Yang, MC
   Guan, HP
   Liu, ZY
   Zhao, SG
   Takeuchi, S
   Yanagisawa, D
   Tooyama, I
AF Yang, Hongkuan
   Yang, Mingchun
   Guan, Hongpeng
   Liu, Ziyi
   Zhao, Shiguang
   Takeuchi, Shigeko
   Yanagisawa, Daijiro
   Tooyama, Ikuo
TI Mitochondrial ferritin in neurodegenerative diseases
SO NEUROSCIENCE RESEARCH
LA English
DT Review
DE d Iron; Transition metal; Alzheimer's disease, Restless legs syndrome;
   Substantia nigra; Oxidative stress
ID RESTLESS LEGS SYNDROME; DIVALENT METAL TRANSPORTER-1; INDUCED OXIDATIVE
   STRESS; IRON-RESPONSIVE ELEMENT; CENTRAL-NERVOUS-SYSTEM; REDOX-ACTIVE
   IRON; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; HUMAN-BRAIN; TRANSFERRIN
   RECEPTOR
AB Mitochondrial ferritin (FtMt) is a novel protein encoded by an intronless gene mapped to chromosome 5q23.1. Ferritin is ubiquitously expressed; however, FtMt expression is restricted to specific tissues such as the testis and the brain. The distribution pattern of FtMt suggests a functional role for this protein in the brain; however, data concerning the roles of FtMt in neurodegenerative diseases remain scarce. In the human cerebral cortex, FtMt expression was increased in Alzheimer's disease patients compared to control cases. Cultured neuroblastoma cells showed low-level expression of FtMt, which was increased by H2O2 treatment. FtMt overexpression showed a neuroprotective effect against H2O2-induced oxidative stress and A beta-induced neurotoxicity in neuroblastoma cells. FtMt expression was also detected in dopaminergic neurons in the substantia nigra and was increased in patients with restless legs syndrome, while FtMt had a protective effect against cell death in a neuroblastoma cell line model of Parkinson's disease. FtMt is involved in other neurodegenerative diseases such as age-related macular degeneration (AMD), with an FtMt gene mutation identified in AMD patients, and Friedreich's ataxia, which is caused by a deficiency in frataxin. FtMt overexpression in frataxin-deficient cells increased cell resistance to H2O2 damage. These results implicate a neuroprotective role of FtMt in neurodegenerative diseases. (C) 2013 The Authors. Published by Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
C1 [Yang, Hongkuan; Yang, Mingchun; Guan, Hongpeng; Liu, Ziyi; Takeuchi, Shigeko; Yanagisawa, Daijiro; Tooyama, Ikuo] Shiga Univ Med Sci, Mol Neurosci Res Ctr, Otsu, Shiga 5202192, Japan.
   [Yang, Hongkuan; Yang, Mingchun; Guan, Hongpeng; Liu, Ziyi; Zhao, Shiguang] Harbin Med Univ, Affiliated Hosp 1, Dept Neurosurg, Harbin 150001, Peoples R China.
C3 Shiga University of Medical Science; Harbin Medical University
RP Tooyama, I (通讯作者)，Shiga Univ Med Sci, Mol Neurosci Res Ctr, Seta Tsukinowa Cho, Otsu, Shiga 5202192, Japan.
EM kinchan@belle.shiga-med.ac.jp
OI Tooyama, Ikuo/0000-0001-8054-9666
FU Ministry of Education, Science, Sports and Culture of Japan;
   Grants-in-Aid for Scientific Research [24111522, 24590400] Funding
   Source: KAKEN
FX This work was supported by the Grant-in-Aid for Scientific Research on
   Innovative Areas ("Brain Environment") from the Ministry of Education,
   Science, Sports and Culture of Japan (I.T.).
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NR 89
TC 45
Z9 46
U1 2
U2 31
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0168-0102
EI 1872-8111
J9 NEUROSCI RES
JI Neurosci. Res.
PD SEP-OCT
PY 2013
VL 77
IS 1-2
BP 1
EP 7
DI 10.1016/j.neures.2013.07.005
PG 7
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 254NF
UT WOS:000327171700001
PM 23916831
OA hybrid
DA 2022-11-30
ER

PT J
AU Yu, CC
   Nandrot, EF
   Dun, Y
   Finnemann, SC
AF Yu, Chia-Chia
   Nandrot, Emeline F.
   Dun, Ying
   Finnemann, Silvia C.
TI Dietary antioxidants prevent age-related retinal pigment epithelium
   actin damage and blindness in mice lacking alpha v beta 5 integrin
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Actin; Age-related blindness; Antioxidant; Cytoskeleton;
   4-Hydroxynonenal; Lipotuscin; Oxidative stress; Protein oxidation;
   Retina; Retinal pigment epithelium; Free radicals
ID MACULAR DEGENERATION; INDUCED INFLAMMATION; LIPOFUSCIN GRANULES;
   OXIDATIVE DAMAGE; FOCAL ADHESION; CELLS; A2E; PHAGOCYTOSIS; DYSFUNCTION;
   PROTEINS
AB In the aging human eye, oxidative damage and accumulation of pro-oxidant lysosomal lipofuscin cause functional decline of the retinal pigment epithelium (RPE), which contributes to age-related macular degeneration. In mice with an RPE-specific phagocytosis defect due to lack of alpha v beta 5 integrin receptors, RPE accumulation of lipofuscin suggests that the age-related blindness we previously described in this model may also result from oxidative stress. Cellular and molecular targets of oxidative stress in the eye remain poorly understood. Here we identify actin among 4-hydroxynonenal (HNE) adducts formed specifically in beta 5(-/-) RPE but not in neural retina with age. HNE modification directly correlated with loss of resistance of actin to detergent extraction, suggesting cytoskeletal damage in aging RPE. Dietary enrichment with natural antioxidants, grapes or marigold extract containing macular pigments lutein/zeaxanthin, was sufficient to prevent HNE-adduct formation, actin solubility, lipofuscin accumulation, and age-related cone and rod photoreceptor dysfunction in beta 5(-/-) mice. Acute generation of HNE adducts directly destabilized actin but not tubulin cytoskeletal elements of RPE cells. These findings identify destabilization of the actin cytoskeleton as a consequence of a physiological, sublethal oxidative burden of RPE cells in vivo that is associated with age-related blindness and that can be prevented by consuming an antioxidant-rich diet. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Yu, Chia-Chia; Dun, Ying; Finnemann, Silvia C.] Fordham Univ, Dept Biol Sci, Bronx, NY 10458 USA.
   [Nandrot, Emeline F.] INSERM, U968, F-75012 Paris, France.
   [Nandrot, Emeline F.] Univ Paris 06, Inst Vis, UMR S 968, F-75012 Paris, France.
   [Nandrot, Emeline F.] CNRS, UMR 7210, F-75012 Paris, France.
C3 Fordham University; Institut National de la Sante et de la Recherche
   Medicale (Inserm); UDICE-French Research Universities; Sorbonne
   Universite; Centre National de la Recherche Scientifique (CNRS); CNRS -
   National Institute for Biology (INSB); UDICE-French Research
   Universities; Universite Paris Cite
RP Finnemann, SC (通讯作者)，Fordham Univ, Dept Biol Sci, Bronx, NY 10458 USA.
EM finnemann@fordham.edu
RI Nandrot, Emeline F./AAN-3925-2020
OI Nandrot, Emeline/0000-0003-3087-078X
FU National Institutes of Health, National Eye Institute [EY013295];
   California Table Grape Commission; Institut National de la Sante et de
   la Recherche Medicale; Universite Pierre et Marie Curie-Paris; Centre
   National de la Recherche Scientifique; Department de Paris; Fondation
   Voir et Entendre; Fondation Bettencourt Schueller; NATIONAL EYE
   INSTITUTE [R01EY013295] Funding Source: NIH RePORTER
FX We thank Ms. Kathryn Silva for excellent technical support. We thank Dr.
   Zoraida Freitas from Kemin Health for generously supplying the FloraGlo
   lutein/zeaxanthin mix. This work was supported by National Institutes of
   Health Grant EY013295 from the National Eye Institute (to S.C.F.) and a
   Research Award by The California Table Grape Commission (to S.C.F.).
   E.F.N. was supported by the Institut National de la Sante et de la
   Recherche Medicale, the Universite Pierre et Marie Curie-Paris 6, the
   Centre National de la Recherche Scientifique, and the Department de
   Paris (to Institut de la Vision) and by Young Investigator Grants from
   the Fondation Voir et Entendre and Fondation Bettencourt Schueller.
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NR 40
TC 48
Z9 48
U1 1
U2 22
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD FEB 1
PY 2012
VL 52
IS 3
BP 660
EP 670
DI 10.1016/j.freeradbiomed.2011.11.021
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 885UA
UT WOS:000299805100010
PM 22178979
OA Green Accepted, Green Published
DA 2022-11-30
ER

PT J
AU Kaiser, RS
   Gupta, OP
   Regillo, CD
   Ho, AC
   Fineman, MS
   Vander, JF
   McNamara, JA
   Brown, GC
AF Kaiser, Richard S.
   Gupta, Omesh P.
   Regillo, Carl D.
   Ho, Allen C.
   Fineman, Mitchell S.
   Vander, James F.
   McNamara, J. Arch
   Brown, Gary C.
TI Ranibizumab for Eyes Previously Treated With Pegaptanib or Bevacizumab
   Without Clinical Response
SO OPHTHALMIC SURGERY LASERS & IMAGING
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; CHOROIDAL
   NEOVASCULARIZATION; PHARMACOKINETICS; THERAPY; INJECTION; ANTIBODY;
   FRAGMENT; AVASTIN; RABBITS
AB BACKGROUND AND OBJECTIVE: To assess the safety and efficacy of ranibizumab in patients who had inadequate response to pegaptanib or bevacizumab.
   PATIENTS AND METHODS: In this single-center study, 19 patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) previously treated with pegaptanib (n = 1), bevacizumab (n = 13), or both (n = 5) received 12 monthly ranibizumab injections (0.5 mg). Outcomes were measured from start of previous therapy (baseline) to start of ranibizumab treatment (day 0) through 12 months.
   RESULTS: No drug-or injection-related adverse events and no serious adverse events were reported. At 6 and 12 months, 4 and 5 patients gained 3 or more lines of VA, respectively; 3 patients lost less than 3 lines of VA at 6 months, and 6 patients lost less than 3 lines at 12 months. At 6 and 12 months, VA increased by a mean (+/- standard error of the mean) of 2.06 +/- 1.23 and 1.17 +/- 0.62 lines, respectively. Central retinal thickness decreased by a mean of 62.65 +/- 22.46 and 62.16 +/- 29.20 mu m at months 6 and 12, respectively. When stratified by pigment epithelial detachment (PED) status, patients without PED had better visual and anatomical outcomes than patients with PED.
   CONCLUSION: Ranibizumab has favorable safety and efficacy profiles for patients with AMD without previous response to pegaptanib or bevacizumab.
C1 [Kaiser, Richard S.; Gupta, Omesh P.; Regillo, Carl D.; Ho, Allen C.; Fineman, Mitchell S.; Vander, James F.; McNamara, J. Arch; Brown, Gary C.] Thomas Jefferson Univ, Wills Eye Inst, Retina Serv, Philadelphia, PA 19107 USA.
C3 Jefferson University
RP Kaiser, RS (通讯作者)，Mid Atlantic Retina, 501 Cooper Landing Rd, Cherry Hill, NJ 08002 USA.
EM kaiserrick@aol.com
OI Ho, Allen/0000-0003-3921-608X
FU Genentech, Inc.
FX Supported by a grant from Genentech, Inc. Third-party medical writing
   assistance for this manuscript was supported by Genentech, Inc.
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NR 18
TC 13
Z9 14
U1 0
U2 1
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 1542-8877
J9 OPHTHAL SURG LAS IM
JI Ophthalmic Surg. Lasers Imaging
PD JAN-FEB
PY 2012
VL 43
IS 1
BP 13
EP 19
DI 10.3928/15428877-20111006-01
PG 7
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA 959VA
UT WOS:000305342600002
PM 21986085
DA 2022-11-30
ER

PT J
AU Zhou, YD
   Sheets, KG
   Knott, EJ
   Regan, CE
   Tuo, JS
   Chan, CC
   Gordon, WC
   Bazan, NG
AF Zhou, Yongdong
   Sheets, Kristopher G.
   Knott, Eric J.
   Regan, Cornelius E., Jr.
   Tuo, Jingsheng
   Chan, Chi-Chao
   Gordon, William C.
   Bazan, Nicolas G.
TI Cellular and 3D optical coherence tomography assessment during the
   initiation and progression of retinal degeneration in the
   Ccl2/Cx3cr1-deficient mouse
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Ccl2; Cx3cr1; rodent model; confocal scanning laser ophthalmoscopy;
   optical coherence tomography; 3D OCT; photoreceptor degeneration;
   reactive gliosis; Muller cell
ID PHOTORECEPTOR DEGENERATION; RETINITIS-PIGMENTOSA; PROTEIN EXPRESSION;
   ANIMAL-MODEL; LIGHT; MICE; CX3CR1; DEFICIENT; DAMAGE; ACCUMULATION
AB Retinal pathologies common to human eye diseases, including abnormal retinal pigment epithelial (RPE) cells, drusen-like accumulation, photoreceptor atrophy, and choroidal neovascularization, have been reported in the Ccl2/Cx3cr1-deficient mouse. The Ccl2 gene encodes the pro-inflammatory chemokine CCL2 (MCP-1), which is responsible for chemotactic recruitment of monocyte-derived macrophages to sites of inflammation. The Cx3cr1 gene encodes the fractalkine receptor, CX3CR1, and is required for accumulation of monocytes and microglia recruited via CCL2. Chemokine-mediated inflammation is implicated in retinal degenerative diseases such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and uveoretinitis, and proper chemokine signaling from the RPE, Muller glia, and astrocytes is necessary to regulate leukocyte trafficking. Therefore, this mouse, possessing aberrant chemokine signaling coupled with retinal degenerative pathologies, presents an ideal opportunity to investigate the effect of altered signaling on retinal homeostasis and photoreceptor degeneration. Since this mouse is a recent development, more data covering the onset, location, and progression rate of pathologies is needed. In the present study we establish these parameters and show two photoreceptor cell death processes. Our observations of decreased glutamine synthetase and increased glial fibrillary acidic protein suggest that Muller cells respond very early within regions where lesions are forming. Finally, we suggest that retinal angiomatous proliferation contributes to pathological angiogenesis in this Ccl2/Cx3cr1-deficient mouse. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Bazan, Nicolas G.] Louisiana State Univ, Sch Med, Dept Ophthalmol, Hlth Sci Ctr,Neurosci Ctr Excellence, New Orleans, LA 70112 USA.
   [Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
C3 Louisiana State University System; Louisiana State University Health
   Sciences Center New Orleans; National Institutes of Health (NIH) - USA;
   NIH National Eye Institute (NEI)
RP Bazan, NG (通讯作者)，Louisiana State Univ, Sch Med, Dept Ophthalmol, Hlth Sci Ctr,Neurosci Ctr Excellence, 2020 Gravier St,Suite D, New Orleans, LA 70112 USA.
EM nbazan@lsuhsc.edu
RI Bazan, Nicolas/AAN-4121-2020
OI Bazan, Nicolas/0000-0002-9243-5444; Tuo, Jingsheng/0000-0002-1372-7810;
   Sheets, Kristopher/0000-0003-0923-4068
FU National Institutes of Health, NCRR [P20 RR016816]; NEI [R01 EY005121];
   American Health Assistance Foundation [M2010091]; Foundation Fighting
   Blindness [TA-NP-0808-0463-LSUNO]; NATIONAL CENTER FOR RESEARCH
   RESOURCES [P20RR016816] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [ZIAEY000418, F31EY020115, R01EY005121, ZIAEY000222] Funding
   Source: NIH RePORTER
FX This research was supported by grants from the National Institutes of
   Health, NCRR (P20 RR016816) and NEI (R01 EY005121), the American Health
   Assistance Foundation (M2010091), and the Foundation Fighting Blindness
   (TA-NP-0808-0463-LSUNO).
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NR 39
TC 22
Z9 23
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 NOV
PY 2011
VL 93
IS 5
BP 636
EP 648
DI 10.1016/j.exer.2011.07.017
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 855AK
UT WOS:000297535700010
PM 21854772
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Moutray, T
   Alarbi, M
   Mahon, G
   Stevenson, M
   Chakravarthy, U
AF Moutray, T.
   Alarbi, M.
   Mahon, G.
   Stevenson, M.
   Chakravarthy, U.
TI Relationships between clinical measures of visual function, fluorescein
   angiographic and optical coherence tomography features in patients with
   subfoveal choroidal neovascularisation
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID DIABETIC MACULAR EDEMA; INTRAVITREAL BEVACIZUMAB AVASTIN; PHOTODYNAMIC
   THERAPY; DEGENERATION; VERTEPORFIN; PATTERNS; ACUITY
AB Aims: To examine the relationships between measures of vision, optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) characteristics in patients with exudative age-related macular degeneration (AMD).
   Study design: Retrospective case note review. Inclusion criteria were: confirmed diagnosis of new exudative AMD; recorded visual function using best corrected distance visual acuity (DVA), near visual acuity (NVA) and contrast sensitivity; corresponding FFA and OCT. FFA parameters included greatest linear diameter of lesion (GLD), area of choroidal neovascularisation (CNV) and area of leakage. OCT parameters included maximum retinal thickness (Ret(max)), central foveal thickness, maximum thickness of the CNV (CNVmax), and the distances from the foveal depression to Ret(max) and CNVmax.
   Results: 74 patients were included in this study. Correlations were highly statistically significant for both NVA and contrast sensitivity with GLD, CNV area and leakage (p<0.01 for all combinations). With DVA, modest statistically significant correlations were seen with CNV area and GLD (p<0.05). There was a statistically significant correlation between CNV leakage and the distance of CNVmax to the fovea (p<0.05). The relationships between the measures of vision and OCT parameters were weak and did not reach significance. Regression analysis showed that the combination of Ret(max), GLD, and CNVmax to fovea had the highest coefficient (r(2) = 0.27).
   Conclusion: OCT measurements by themselves are not robust markers for visual function.
C1 [Chakravarthy, U.] Queens Univ Belfast, Ctr Vis Sci, Belfast, Antrim, North Ireland.
   [Moutray, T.; Alarbi, M.; Mahon, G.; Chakravarthy, U.] Royal Victoria Hosp, Directorate Ophthalmol, Head & Skeletal Div, Belfast BT12 6BA, Antrim, North Ireland.
   [Stevenson, M.] Queens Univ Belfast, Ctr Populat Sci, Belfast, Antrim, North Ireland.
C3 Queens University Belfast; Queens University Belfast
RP Chakravarthy, U (通讯作者)，Queens Univ Belfast, Ctr Vis Sci, Belfast, Antrim, North Ireland.
EM u.chakravarthy@qub.ac.uk
OI Chakravarthy, Usha/0000-0002-2606-3734
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NR 16
TC 61
Z9 63
U1 0
U2 2
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 MAR
PY 2008
VL 92
IS 3
BP 361
EP 364
DI 10.1136/bjo.2007.123976
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 274HG
UT WOS:000253991800015
PM 18303157
DA 2022-11-30
ER

PT J
AU Rosenthal, R
   Heimann, H
   Agostini, H
   Martin, G
   Hansen, LL
   Strauss, O
AF Rosenthal, Rita
   Heimann, Heinrich
   Agostini, Hansjuergen
   Martin, Gottfried
   Hansen, Lutz Lothar
   Strauss, Olaf
TI Ca2+ channels in retinal pigment epithelial cells regulate vascular
   endothelial growth factor secretion rates in health and disease
SO MOLECULAR VISION
LA English
DT Article
ID CHOROIDAL NEOVASCULAR MEMBRANES; PROTEIN-TYROSINE KINASE; MACULAR
   DEGENERATION; CALCIUM-CHANNELS; IGFBP-3 SECRETION; BRAIN NEURONS;
   CULTURED RAT; FACTOR-I; VOLTAGE; EXPRESSION
AB PURPOSE: Choroidal neovascularization (CNV) is the most severe complication in age-related macular degeneration. The major angiogenic factor involved is vascular endothelial growth factor (VEGF) secreted by the retinal pigment epithelium (RPE). Since RPE cells express neuroendocrine L-type Ca2+ channels we investigated their involvement in VEGF secretion in normal RPE cells and RPE cells from patients with CNV.
   METHODS: Freshly isolated and cultured RPE cells were studied using the patch-clamp technique and ELISA-based secretion assays.
   RESULTS: Both freshly isolated and cultured cells showed whole-cell Ba2+ currents with properties of L-type Ca2+ currents: high activation threshold, sensitivity to dihydropyridines (10 mu M nifedipine) and slow inactivation. VEGF-A secretion was elevated by BayK8644 (10 mu M) or basic fibroblast growth factor (bFGF, 10 ng/ml), both of which are able to activate L-type channels. Cells from CNV tissue also showed nifedipine-sensitive Ba2+ currents, which displayed a voltage-dependent activation at more negative potentials, faster inactivation and changed regulation by tyrosine kinase pp60(c-src). The CNV RPE cells showed higher VEGF secretion rates which were reduced by nifedipine.
   CONCLUSIONS: Thus, L-type Ca2+ channels in normal RPE cells regulate the secretion of VEGF. RPE cells from eyes with CNV maintain a VEGF secretion regulated by nifedipine-sensitve Ca2+ channels which might be of importance for the development of CNV.
C1 Univ Hamburg, Klinikum Eppendorf, Klin & Poliklin Augenheilkunde, D-20246 Hamburg, Germany.
   Univ Med Berlin, Charite, Inst Klin Physiol, Berlin, Germany.
   Royal Liverpool Hosp, St Pauls Eye Unit, Liverpool L7 8XP, Merseyside, England.
   Univ Freiburg Klinikum, Augenklin, Freiburg, Germany.
C3 University of Hamburg; Free University of Berlin; Humboldt University of
   Berlin; Charite Universitatsmedizin Berlin; Royal Liverpool & Broadgreen
   University Hospitals NHS Trust; Royal Liverpool University Hospital;
   University of Freiburg; University of Hamburg; University Medical Center
   Hamburg-Eppendorf
RP Strauss, O (通讯作者)，Univ Hamburg, Klinikum Eppendorf, Klin & Poliklin Augenheilkunde, Martinistr 52, D-20246 Hamburg, Germany.
EM o.strauss@uke.uni-hamburg.de
RI Rosenthal, Rita/M-5652-2014; Hansen, Lutz L/A-1390-2011; Heimann,
   Heinrich/AAP-8747-2020; Strauss, Olaf/AAA-6485-2019
OI Heimann, Heinrich/0000-0002-3298-4644; Strauss, Olaf/0000-0002-6272-8596
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NR 54
TC 50
Z9 59
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 MAR 27
PY 2007
VL 13
IS 47-49
BP 443
EP 456
PG 14
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 154LU
UT WOS:000245509700001
PM 17417605
DA 2022-11-30
ER

PT J
AU Rogers, AH
   Duker, JS
   Nichols, N
   Baker, BJ
AF Rogers, AH
   Duker, JS
   Nichols, N
   Baker, BJ
TI Photodynamic therapy of idiopathic and inflammatory choroidal
   neovascularization in young adults
SO OPHTHALMOLOGY
LA English
DT Article
ID PUNCTATE INNER CHOROIDOPATHY
AB Purpose: To evaluate the treatment of subfoveal choroidal neovascularization (CNV) using photodynamic therapy (PDT) with verteporfin (Visudyne; Novartis, Duluth, GA) in young adults.
   Design: Retrospective noncomparative interventional case series.
   Participants: Nineteen eyes of 17 patients with classic, subfoveal CNV treated with PDT using verteporfin, excluding eyes with CNV secondary to age-related macular degeneration, angioid streaks, and myopia.
   Main Outcome Measures: Snellen visual acuity before and after PDT.
   Results: Nineteen eyes were followed an average of 12.8 months (range, 4-33 months) after PDT. Before treatment, visual acuity measured greater than or equal to20/40 in 0 eyes (0.0%), <20/40 to >20/200 in 11 eyes (57.9%), and less than or equal to20/200 in 8 eyes (42.1%). After treatment, visual acuity measured greater than or equal to20/40 in four eyes (21.1%), <20/40 to >20/200 in eight eyes (42.1%), and less than or equal to20/200 in seven eyes (36.8%). Six eyes (31.6%) underwent retreatment, with only two eyes retreated twice. Four eyes underwent eventual surgical removal of the CNV after PDT.
   Conclusions: Photodynamic therapy seems to be useful in stabilizing and improving visual acuity in young adults with subfoveal CNV secondary to idiopathic and inflammatory etiologies. (C) 2003 by the American Academy of Ophthalmology.
C1 Tufts Univ, New England Eye Ctr, Sch Med, Boston, MA 02111 USA.
C3 Tufts University
RP Duker, JS (通讯作者)，Tufts Univ, New England Eye Ctr, Sch Med, 750 Washington St,Box 450, Boston, MA 02111 USA.
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NR 16
TC 53
Z9 59
U1 1
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 JUL
PY 2003
VL 110
IS 7
BP 1315
EP 1320
DI 10.1016/S0161-6420(03)00466-4
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 700DK
UT WOS:000184097200022
PM 12867384
DA 2022-11-30
ER

PT J
AU Li, HX
   Zhu, XY
   Wang, MJ
   Zhao, DY
   Li, HL
   Yan, J
AF Li, Hongxia
   Zhu, Xinyu
   Wang, Minjie
   Zhao, Danyang
   Li, Honglin
   Yan, Jun
TI Drug sustained release from degradable drug-loaded in-situ hydrogels in
   the posterior eye: A mechanistic model and analytical method
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Biodegradable hydrogels; Drug delivery; The posterior eye; Macular
   disease; Numerical simulation
ID CONTROLLED ANTIBODY RELEASE; DIELS-ALDER HYDROGELS; DIFFUSIVE TRANSPORT;
   PROTEIN DELIVERY; MESH SIZE; INTRAVITREAL; BEVACIZUMAB; STABILITY;
   INJECTION; CARRIERS
AB Biodegradable in-situ hydrogels as drug release carriers injected into the eye can treat Neovascular age-related macular degeneration (NV-AMD). Obviously, the biodegradation behavior of hydrogels affects the drug diffusion process in the eye, which can influence the drug concentration distribution and development in the macula. Herein, the intraocular diffusion process of the drugs which are released from the biodegradable hydrogel was studied by using finite element method, with the effect of the biodegradation behavior of hydrogels on the drug release process was considered. The effects of the initial average mesh size, rate constant of biodegradation, and position of hydrogels on the drug release process were analyzed. The results showed that the biodegradation behavior of hydrogels decreases the drug release rate by gradually expanding the mesh size, prolonging the duration of drug treatment in the macula. The biodegradable hydrogels' position, initial mesh size, and biodegradation rate constant also affect drug delivery. Different locations of hydrogels denote different distances between the drug and macula, which affects the diffusion time and further influence the macular drug concentration. The initial mesh size alters the initial drug release rate, which affects the duration of hydrogels' drug release process and drug concentration and duration in the macula. The hydrogel degradation rate affects the development of its mesh size, which affects the drug diffusion in hydrogels, and further affects the drug concentration in the macular region.
C1 [Li, Hongxia; Zhu, Xinyu; Wang, Minjie; Zhao, Danyang] Dalian Univ Technol, Key Lab Precis & Nontradit Machining Technol, Minist Educ, Dalian 116023, Liaoning, Peoples R China.
   [Li, Honglin] East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China.
   [Yan, Jun] Dalian Univ Technol, Dept Engn Mech, State Key Lab Struct Anal Ind Equipment, Dalian 116023, Peoples R China.
C3 Dalian University of Technology; East China University of Science &
   Technology; Dalian University of Technology
RP Li, HX (通讯作者)，Dalian Univ Technol, Key Lab Precis & Nontradit Machining Technol, Minist Educ, 2 Linggong Rd, Dalian 116024, Peoples R China.
EM hxli@dlut.edu.cn
FU National Natural Science Foundation of China [11502044, U1906233];
   Fundamental Research Funds for the Central Universities [DUT17RC(3)
   104]; National Key R&D Program of China [2018YFA0703, 2019YFA0708804]
FX The authors greatly appreciate the financial support by the National
   Natural Science Foundation of China (11502044, U1906233), the
   Fundamental Research Funds for the Central Universities (DUT17RC(3) 104)
   and the National Key R&D Program of China(2018YFA0703, 2019YFA0708804).
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NR 35
TC 0
Z9 0
U1 9
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9290
EI 1873-2380
J9 J BIOMECH
JI J. Biomech.
PD MAY
PY 2022
VL 136
AR 111052
DI 10.1016/j.jbiomech.2022.111052
PG 10
WC Biophysics; Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biophysics; Engineering
GA 2R3TF
UT WOS:000821034500003
PM 35349869
DA 2022-11-30
ER

PT J
AU Leger-Charnay, E
   Gambert, S
   Martine, L
   Dubus, E
   Maire, MA
   Buteau, B
   Morala, T
   Gigot, V
   Bron, AM
   Bretillon, L
   Masson, EAY
AF Leger-Charnay, Elise
   Gambert, Segolene
   Martine, Lucy
   Dubus, Elisabeth
   Maire, Marie-Annick
   Buteau, Benedicte
   Morala, Tristan
   Gigot, Vincent
   Bron, Alain M.
   Bretillon, Lionel
   Masson, Elodie A. Y.
TI Retinal cholesterol metabolism is perturbated in response to
   experimental glaucoma in the rat
SO PLOS ONE
LA English
DT Article
ID POLYUNSATURATED FATTY-ACIDS; GLIAL-CELLS; INTRAOCULAR-PRESSURE;
   APOLIPOPROTEIN-E; MOUSE RETINA; CYP46A1; ELEVATION; RECEPTOR; DIETARY;
   NEUROINFLAMMATION
AB Alterations of cholesterol metabolism have been described for many neurodegenerative pathologies, such as Alzheimer's disease in the brain and age-related macular degeneration in the retina. Recent evidence suggests that glaucoma, which is characterized by the progressive death of retinal ganglion cells, could also be associated with disruption of cholesterol homeostasis. In the present study we characterized cholesterol metabolism in a rat model of laser-induced intraocular hypertension, the main risk factor for glaucoma. Sterol levels were measured using gas-chromatography and cholesterol-related gene expression using quantitative RT-PCR at various time-points. As early as 18 hours after the laser procedure, genes implicated in cholesterol biosynthesis and uptake were upregulated (+49% and +100% for HMG-CoA reductase and LDLR genes respectively, vs. naive eyes) while genes involved in efflux were downregulated (-26% and -37% for ApoE and CYP27A1 genes, respectively). Cholesterol and precursor levels were consecutively elevated 3 days post-laser (+14%, +40% and +194% for cholesterol, desmosterol and lathosterol, respectively). Interestingly, counter-regulatory mechanisms were transcriptionally activated following these initial dysregulations, which were associated with the restoration of retinal cholesterol homeostasis, favorable to ganglion cell viability, one month after the laser-induced ocular hypertension. In conclusion, we report here for the first time that ocular hypertension is associated with transient major dynamic changes in retinal cholesterol metabolism.
C1 [Leger-Charnay, Elise; Gambert, Segolene; Martine, Lucy; Dubus, Elisabeth; Maire, Marie-Annick; Buteau, Benedicte; Morala, Tristan; Gigot, Vincent; Bron, Alain M.; Bretillon, Lionel; Masson, Elodie A. Y.] Univ Bourgogne Franche Comte, Ctr Sci Gout & Alimentat, INRAE, CNRS,AgroSup Dijon, Dijon, France.
   [Gambert, Segolene] Plateforme Biol Hosp Univ, Lab Biochim Med, Dijon, France.
   [Bron, Alain M.] Ctr Hosp Univ Dijon, Dept Ophtalmol, Dijon, France.
C3 INRAE; Institut Agro; AgroSup Dijon; Centre National de la Recherche
   Scientifique (CNRS); Universite de Bourgogne; CHU Dijon Bourgogne; CHU
   Dijon Bourgogne
RP Masson, EAY (通讯作者)，Univ Bourgogne Franche Comte, Ctr Sci Gout & Alimentat, INRAE, CNRS,AgroSup Dijon, Dijon, France.
EM elodie.masson@inrae.fr
OI Bron, Alain/0000-0002-7265-931X
FU Institut National de la Recherche Agronomique; Conseil Regional
   Bourgogne, Franche-Comte (PARI grant); FEDER (European Funding for
   Regional Economical Development); Fondation de France/Fondation de
   l'oeil; Ministere de l'Enseignement Superieur, de la Recherche et de
   l'Innovation; Universite de Bourgogne Franche-Comte; Nouvelle Societe
   Francaise d'Atherosclerose
FX This work was supported by grants from the Institut National de la
   Recherche Agronomique; the Conseil Regional Bourgogne, Franche-Comte
   (PARI grant); the FEDER (European Funding for Regional Economical
   Development); the Fondation de France/Fondation de l'oeil; the Ministere
   de l'Enseignement Superieur, de la Recherche et de l'Innovation; the
   Universite de Bourgogne Franche-Comte; and the Nouvelle Societe
   Francaise d'Atherosclerose. The funders had no role in study design,
   data collection and interpretation, or the decision to submit the work
   for publication. 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 1
Z9 1
U1 3
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 MAR 11
PY 2022
VL 17
IS 3
AR e0264787
DI 10.1371/journal.pone.0264787
PG 20
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 4H6NN
UT WOS:000849994500025
PM 35275950
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Tawfeeq, GSH
   Kakey, IS
AF Tawfeeq, Govand S. H.
   Kakey, Ismail S.
TI Melatonin's Antioxidative Characteristic in Human Aging Retinal Pigment
   Epithelial Cells
SO INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE Melatonin; retinal pigment epithelial; oxidative biomarkers; real-time
   polymerase chain reaction
ID OXIDATIVE STRESS; PROTECTS; DEGENERATION; LIGHT
AB In this study, the antioxidative effect of melatonin was investigated in aging retinal pigment epithelial cells in vitro. The objective of this study is to explore the administration of melatonin pharmacological doses for the prevention of aging symptoms. Specific concentrations of melatonin (20 mu M, 40 mu M and 80 mu M) were used to treat hydrogen peroxide-induced aging retinal pigment epithelial cells and flow cytometry was employed to examine retinal pigment epithelial cell apoptosis. A specific probe was utilized to detect the intracellular reactive oxygen species concentration and apoptosis-associated proteins were detected in real-time polymerase chain reaction. Commercially available assay kits detected the expression of oxidative biomarkers, superoxide dismutase, malondialdehyde and glutathione. In comparison to normal cells, the aging retinal pigment epithelial cell model had lower cell viability, higher apoptosis rates and a more severe oxidation status. Melatonin increased cell viability while lowering apoptosis and oxidative stress. It influenced the expression of apoptosis-related proteins as well as oxidative stress indicators. Finally, treatment with melatonin was able to regulate proliferation, oxidative stress and apoptosis in aging retinal pigment epithelial cells. The application of melatonin may be a novel strategy to protect against age-related changes in age-related macular degeneration. Melatonin has protective effects against hydrogen peroxide-induced retinal cell death. It inhibits hydrogen peroxide-induced retinal pigment epithelial cell damage and decreases the apoptosis rate.
C1 [Tawfeeq, Govand S. H.] Hawler Med Univ, Coll Pharm, Dept Clin Anal, Erbil, Kurdistan Regio, Iraq.
   [Kakey, Ismail S.] Koya Univ, Fac Sci & Hlth, Dept Biol, KOY45, Koya, Kurdistan Regio, Iraq.
C3 Hawler Medical University; Koya University
RP Tawfeeq, GSH (通讯作者)，Hawler Med Univ, Coll Pharm, Dept Clin Anal, Erbil, Kurdistan Regio, Iraq.
EM govand.tawfeeq@hmu.edu.krd
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TC 0
Z9 0
U1 2
U2 2
PU INDIAN PHARMACEUTICAL ASSOC
PI MUMBAI
PA KALINA, SANTA CRUZ EAST, MUMBAI, 00000, INDIA
SN 0250-474X
EI 1998-3743
J9 INDIAN J PHARM SCI
JI Indian J. Pharm. Sci.
PY 2022
VL 84
SI 3
BP 64
EP 70
DI 10.36468/pharmaceutical-sciences.spl.492
PG 7
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 2V0RT
UT WOS:000823561100008
OA hybrid
DA 2022-11-30
ER

PT J
AU Sim, SS
   Yip, MYT
   Wang, ZR
   Tan, ACS
   Tan, GSW
   Cheung, CMG
   Chakravarthy, U
   Wong, TY
   Teo, KYC
   Ting, DSW
AF Sim, Shaun Sebastian
   Yip, Michelle Y. T.
   Wang, Zhaoran
   Tan, Anna Cheng Sim
   Tan, Gavin Siew Wei
   Cheung, Chui Ming Gemmy
   Chakravarthy, Usha
   Wong, Tien Yin
   Teo, Kelvin Yi Chong
   Ting, Daniel S. W.
TI Digital Technology for AMD Management in the Post-COVID-19 New Normal
SO ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE AI; AMD; Covid-19; digital healthcare; telemedicine
AB Purpose: The COVID-19 pandemic has put strain on healthcare systems and the availability and allocation of healthcare manpower, resources and infrastructure. With immediate priorities to protect the health and safety of both patients and healthcare service providers, ophthalmologists globally were advised to defer nonurgent cases, while at the same time managing sight-threatening conditions such as neovascular Age-related Macular Degeneration (AMD). The management of AMD patients both from a monitoring and treatment perspective presents a particular challenge for ophthalmologists. This review looks at how these pressures have encouraged the acceptance and speed of adoption of digitalization.
   Design and methods: A literature review was conducted on the use of digital technology during COVID-19 pandemic, and on the transformation of medicine, ophthalmology and AMD screening through digitalization.
   Results: In the management of AMD, the implementation of artificial intelligence and "virtual clinics" have provided assistance in screening, diagnosis, monitoring of the progression and the treatment of AMD. In addition, hardware and software developments in home monitoring devices has assisted in self-monitoring approaches.
   Conclusions: Digitalization strategies and developments are currently ongoing and underway to ensure early detection, stability and visual improvement in patients suffering from AMD in this COVID-19 era. This may set a precedence for the post COVID-19 new normal where digital platforms may be routine, standard and expected in healthcare delivery.
C1 [Sim, Shaun Sebastian; Yip, Michelle Y. T.; Wang, Zhaoran; Tan, Anna Cheng Sim; Tan, Gavin Siew Wei; Cheung, Chui Ming Gemmy; Wong, Tien Yin; Teo, Kelvin Yi Chong; Ting, Daniel S. W.] Natl Univ Singapore, Duke NUS Med Sch, Singapore Natl Eye Ctr, Singapore, Singapore.
   [Sim, Shaun Sebastian; Yip, Michelle Y. T.; Wang, Zhaoran; Tan, Anna Cheng Sim; Tan, Gavin Siew Wei; Cheung, Chui Ming Gemmy; Wong, Tien Yin; Teo, Kelvin Yi Chong; Ting, Daniel S. W.] Natl Univ Singapore, Duke NUS Med Sch, Singapore Eye Res Inst, Singapore, Singapore.
   [Sim, Shaun Sebastian; Yip, Michelle Y. T.; Wang, Zhaoran; Tan, Anna Cheng Sim; Tan, Gavin Siew Wei; Cheung, Chui Ming Gemmy; Wong, Tien Yin; Teo, Kelvin Yi Chong; Ting, Daniel S. W.] Natl Univ Singapore, Ophthalmol & Visual Sci Acad Clin Program, Duke NUS Med Sch, Singapore, Singapore.
   [Chakravarthy, Usha] Queens Univ Belfast, Royal Victoria Hosp, Belfast, North Ireland.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; Singapore National Eye Center;
   National University of Singapore; Queens University Belfast
RP Ting, DSW (通讯作者)，Natl Univ Singapore, Duke NUS Med Sch, Singapore, Singapore.; Ting, DSW (通讯作者)，Singapore Natl Eye Ctr, Surg Retina, Singapore, Singapore.; Ting, DSW (通讯作者)，Singapore Eye Res Inst, Artificial Intelligence & Digital Innovat, Singapore, Singapore.; Teo, KYC (通讯作者)，11 Third Hosp Ave, Singapore 168751, Singapore.; Teo, KYC (通讯作者)，Singapore Natl Eye Ctr, Med Retina, Singapore, Singapore.
EM kelvin.teo.y.c@singhealth.com.sg; daniel.ting45@gmail.com
RI Wong, Tien Yin/AAC-9724-2020
OI Wong, Tien Yin/0000-0002-8448-1264; Bidwai, Pooja
   Vishal/0000-0002-3077-4395; Teo, Kelvin/0000-0002-7458-7081
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NR 91
TC 12
Z9 12
U1 3
U2 16
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 JAN-FEB
PY 2021
VL 10
IS 1
BP 39
EP 48
DI 10.1097/APO.0000000000000363
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RI6UD
UT WOS:000637043300007
PM 33512827
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Gote, V
   Mandal, A
   Alshamrani, M
   Pal, D
AF Gote, Vrinda
   Mandal, Abhirup
   Alshamrani, Meshal
   Pal, Dhananjay
TI Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery
SO PHARMACEUTICS
LA English
DT Article
DE retinal pigment epithelial cells; sodium iodate; pro-inflammatory
   cytokines; reactive oxygen species; VEGF-A
ID MACULAR DEGENERATION; SODIUM IODATE; DIABETIC-RETINOPATHY; OXIDATIVE
   STRESS; UNITED-STATES; INFLAMMATION; CELLS; FORMULATION; PREVALENCE;
   PROTECTS
AB Neovascular age-related macular degeneration (AMD) is characterized by an increase in reactive oxygen species (ROS) and pro-inflammatory cytokines in the retinal pigment epithelium cells. The primary purpose of this study was the development of a clear, tacrolimus nanomicellar formulation (TAC-NMF) for AMD. The optimized formulation had a mean diameter of 15.41 nm, a zeta potential of 0.5 mV, and an entrapment efficiency of 97.13%. In-vitro cytotoxicity studies revealed the dose-dependent cytotoxicity of TAC-NMF on various ocular cell lines, such as human retinal pigment epithelium (D407), monkey retinal choroidal endothelial (RF/6A) cells, and human corneal epithelium (CCL 20.2) cells. Cellular uptake and in-vitro distribution studies using flow cytometry and confocal microscopy, respectively, indicated an elevated uptake of TAC-NMF in a time-dependent manner. Biocompatibility assay using macrophage RAW 264.7 cell line resulted in low production of inflammatory cytokines such as IL-6, IL-1 beta and TNF-alpha after treatment with TAC-NMF. There was a decrease in ROS in D407 cells pre-treated with sodium iodate (ROS inducing agent) after treating with TAC-NMF and tacrolimus drug. Similarly, there was a reduction in the pro-inflammatory cytokines and VEGF-A in D407 cells pretreated with sodium iodate. This indicates that TAC-NMF could lower pro-inflammatory cytokines and ROS commonly seen in AMD.
C1 [Gote, Vrinda; Mandal, Abhirup; Alshamrani, Meshal; Pal, Dhananjay] Univ Missouri, Sch Pharm, Div Pharmaceut Sci, 2464 Charlotte St, Kansas City, MO 64108 USA.
   [Alshamrani, Meshal] Jazan Univ, Coll Pharm, Dept Pharmaceut, POB 114, Jazan 45142, Saudi Arabia.
C3 University of Missouri System; University of Missouri Kansas City; Jazan
   University
RP Pal, D (通讯作者)，Univ Missouri, Sch Pharm, Div Pharmaceut Sci, 2464 Charlotte St, Kansas City, MO 64108 USA.
EM vrindagote@mail.umkc.edu; abhirupmandal@mail.umkc.edu;
   malshamrani@jazanu.edu.sa; pald@umkc.edu
OI Gote, Vrinda/0000-0002-8967-601X
FU University of Missouri School of Graduate Studies Research Grant
FX This research work was funded by University of Missouri School of
   Graduate Studies Research Grant which was received by Vrinda Gote.
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NR 59
TC 9
Z9 9
U1 1
U2 10
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1999-4923
J9 PHARMACEUTICS
JI Pharmaceutics
PD NOV
PY 2020
VL 12
IS 11
AR 1072
DI 10.3390/pharmaceutics12111072
PG 31
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA OX6WY
UT WOS:000593703600001
PM 33182620
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hanna, RM
   Tran, NT
   Patel, SS
   Hou, J
   Jhaveri, KD
   Parikh, R
   Selamet, U
   Ghobry, L
   Wassef, O
   Barsoum, M
   Bijol, V
   Kalantar-Zadeh, K
   Pai, A
   Amin, A
   Kupperman, B
   Kurtz, IB
AF Hanna, Ramy M.
   Tran, Ngoc-Tram
   Patel, Sapna S.
   Hou, Jean
   Jhaveri, Kenar D.
   Parikh, Rushang
   Selamet, Umut
   Ghobry, Lena
   Wassef, Olivia
   Barsoum, Marina
   Bijol, Vanesa
   Kalantar-Zadeh, Kamyar
   Pai, Alex
   Amin, Alpesh
   Kupperman, Baruch
   Kurtz, Ira B.
TI Thrombotic Microangiopathy and Acute Kidney Injury Induced After
   Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors
   VEGF Blockade-Related TMA After Intravitreal Use
SO FRONTIERS IN MEDICINE
LA English
DT Article
DE intravitreal injections; thrombotic microangiopathy; diabetic
   retinopathy; vascular endothelial growth factor (VEGF); bevacizumab
   (avastin); ranibizumab (Lucentis); aflibercept (Eylea)
ID SEGMENTAL GLOMERULOSCLEROSIS; MACULAR DEGENERATION; CHRONIC PROTEINURIA;
   NEPHROTIC SYNDROME; PRESSURE CHANGES; BLOOD-PRESSURE; FACTOR THERAPY;
   BEVACIZUMAB; DISEASE; PATIENT
AB Vascular endothelial growth factor (VEGF) inhibition can cause worsening hypertension, proteinuria, chronic kidney injury, and glomerular disease. Thrombotic microangiopathy (TMA) and other nephrotic disorders have been reported with systemic VEGF blockade. These same agents are given intravitreally for age-related macular degeneration (AMD) and diabetic retinopathy (DR), albeit at lower doses than those given for systemic indications. Systemic absorption of anti-VEGF agents when given intravitreally has been shown consistently along with evidence of significant intravascular VEGF suppression. While worsening hypertension has only been seen in some large-scale studies, case reports show worsening proteinuria and diverse glomerular diseases. These include TMA-associated lesions like focal and segmental glomerulosclerosis with collapsing features (cFSGS). In this paper, we report three cases of TMA likely associated with the use of intravitreal anti-VEGF therapy. These patients developed the signature lesion of VEGF blockade in a 6 to 11 month time frame after starting intravitreal VEGF inhibitors. The literature is reviewed showing similar cases. Intravitreal VEGF blockade may cause these adverse events in a hitherto unidentified subgroup of patients. Well-controlled prospective observational trials are needed to determine the event rate and identify which subgroups of patients are at increased risk. A registry for patients who develop worsening hypertension, proteinuria exacerbation, and glomerular diseases from intravitreal VEGF blockade is proposed.
C1 [Hanna, Ramy M.; Kalantar-Zadeh, Kamyar; Pai, Alex] Univ Calif UC, Irvine Sch Med, Dept Med, Div Nephrol, Orange, CA USA.
   [Tran, Ngoc-Tram; Patel, Sapna S.] Long Beach Mem Med Ctr, Dept Med, Div Nephrol, Long Beach, CA USA.
   [Hou, Jean] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA.
   [Jhaveri, Kenar D.; Parikh, Rushang] Donald & Barbara Zucker Sch Med Hofstra Northwell, Div Kidney Dis & Hypertens, Great Neck, NY USA.
   [Selamet, Umut] Brigham & Womens Hosp, Dept Internal Med, Div Renal Med, 75 Francis St, Boston, MA 02115 USA.
   [Ghobry, Lena] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
   [Wassef, Olivia; Kurtz, Ira B.] Univ Calif Los Angeles, Dept Med, Div Nephrol, Los Angeles, CA 90024 USA.
   [Barsoum, Marina] Chapman Univ, Sch Pharm, Keck Sch Sci & Technol, Orange, CA USA.
   [Bijol, Vanesa] Donald & Barbara Zucker Sch Med Hofstra Northwell, Dept Pathol, Great Neck, NY USA.
   [Amin, Alpesh] Univ Calif UC Irvine, Dept Med, Orange, CA USA.
   [Kupperman, Baruch] Univ Calif UC Irvine, Herbert Gavin Eye Inst, Dept Ophthalmol, Irvine, CA USA.
   [Kurtz, Ira B.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA USA.
C3 Cedars Sinai Medical Center; Harvard University; Brigham & Women's
   Hospital; Pennsylvania Commonwealth System of Higher Education (PCSHE);
   University of Pittsburgh; University of California System; University of
   California Los Angeles; Chapman University System; Chapman University;
   University of California System; University of California Los Angeles
RP Hanna, RM (通讯作者)，Univ Calif UC, Irvine Sch Med, Dept Med, Div Nephrol, Orange, CA USA.
EM rhannamd81@yahoo.com
RI Kalantar-Zadeh, Kamyar/Q-4734-2018
OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725
FU NIH [R01-DK077162]; Allan Smidt Charitable Fund; Factor Family
   Foundation; Ralph Block Family Foundation; National Institute on Aging
   of the National Institutes of Health [R21-AG047036]; National Institute
   of Diabetes, Digestive and Kidney Disease [R01-DK078106, R01DK096920,
   U01-DK102163, K24-DK091419]
FX IK was supported in part by funds from the NIH (R01-DK077162), the Allan
   Smidt Charitable Fund, the Factor Family Foundation, and the Ralph Block
   Family Foundation. KK-Z was supported by the National Institute on Aging
   of the National Institutes of Health (grant R21-AG047036) and the
   National Institute of Diabetes, Digestive and Kidney Disease (grants
   R01-DK078106, R01DK096920, U01-DK102163, and K24-DK091419), as well as
   philanthropist grants from Mr. Harold Simmons and Mr. Louis Chang.
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NR 50
TC 13
Z9 14
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 OCT 7
PY 2020
VL 7
AR 579603
DI 10.3389/fmed.2020.579603
PG 10
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA OI5ZB
UT WOS:000583355100001
PM 33117836
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Seah, I
   Zhao, XX
   Lin, QY
   Liu, ZP
   Su, SZZ
   Yuen, YS
   Hunziker, W
   Lingam, G
   Loh, XJ
   Su, XY
AF Seah, Ivan
   Zhao, Xinxin
   Lin, Qianyu
   Liu, Zengping
   Su, Steven Zheng Zhe
   Yuen, Yew Sen
   Hunziker, Walter
   Lingam, Gopal
   Loh, Xian Jun
   Su, Xinyi
TI Use of biomaterials for sustained delivery of anti-VEGF to treat retinal
   diseases
SO EYE
LA English
DT Review
ID VERTEPORFIN PLUS RANIBIZUMAB; DIABETIC MACULAR EDEMA; REVERSE THERMAL
   GEL; INTRAVITREAL INJECTION; VEIN OCCLUSION; BEVACIZUMAB AVASTIN;
   CONTROLLED-RELEASE; CHOROIDAL NEOVASCULARIZATION; CLINICAL UTILIZATION;
   POSTERIOR SEGMENT
AB Anti-vascular endothelial growth factors (anti-VEGF) have become the most common treatment modality for many retinal diseases. These include neovascular age-related macular degeneration (n-AMD), proliferative diabetic retinopathy (PDR) and retinal vein occlusions (RVO). However, these drugs are administered via intravitreal injections that are associated with sight-threatening complications. The most feared of these complications is endophthalmitis, a severe infection of the eye with extremely poor visual outcomes. Patients with retinal diseases typically have to undergo multiple injections before achieving the desired therapeutic effect. Each injection incurs the risk of the sight-threatening complications. As such, there has been great interest in developing sustained delivery platforms for anti-VEGF agents to the posterior segment of the eye. In recent years, there have been various strategies that have been conceptualised. These include non-biodegradable implants, nano-formulations and hydrogels. In this review, the barriers of drug delivery to the posterior segment of the eye will be explained. The characteristics of an ideal sustained delivery platform will then be discussed. Finally, the current available strategies will be analysed with the above-mentioned characteristics in mind to determine the advantages and disadvantages of each sustained drug delivery modality. Through the above, this review attempts to provide an overview of the sustained delivery platforms in their various phases of development.
C1 [Seah, Ivan; Yuen, Yew Sen; Lingam, Gopal; Su, Xinyi] Natl Univ Singapore Hosp, Dept Ophthalmol, Singapore, Singapore.
   [Zhao, Xinxin; Liu, Zengping; Hunziker, Walter; Su, Xinyi] ASTAR, IMCB, Singapore, Singapore.
   [Lin, Qianyu; Loh, Xian Jun] ASTAR, IMRE, Singapore, Singapore.
   [Liu, Zengping; Lingam, Gopal; Su, Xinyi] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
   [Liu, Zengping; Su, Xinyi] Singapore Eye Res Inst, Singapore, Singapore.
   [Su, Steven Zheng Zhe; Hunziker, Walter] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.
   [Hunziker, Walter] Natl Univ Singapore, Dept Physiol, Singapore, Singapore.
C3 National University of Singapore; Agency for Science Technology &
   Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology
   (IMCB); Agency for Science Technology & Research (A*STAR); A*STAR -
   Institute of Materials Research & Engineering (IMRE); National
   University of Singapore; National University of Singapore; Singapore
   National Eye Center; Nanyang Technological University & National
   Institute of Education (NIE) Singapore; Nanyang Technological
   University; National University of Singapore
RP Lingam, G; Su, XY (通讯作者)，Natl Univ Singapore Hosp, Dept Ophthalmol, Singapore, Singapore.; Su, XY (通讯作者)，ASTAR, IMCB, Singapore, Singapore.; Loh, XJ (通讯作者)，ASTAR, IMRE, Singapore, Singapore.; Lingam, G; Su, XY (通讯作者)，Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.; Su, XY (通讯作者)，Singapore Eye Res Inst, Singapore, Singapore.
EM gopal_lingam@nuhs.edu.sg; lohxj@imre.a-star.edu.sg; xinyi_su@nuhs.edu.sg
RI Seah, Ivan/AAK-6341-2020; Hunziker, Walter/B-3140-2010; Hunziker,
   Walter/GSM-8190-2022; Liu, Zengping/GQO-9030-2022; Loh, Xian
   Jun/H-6260-2013
OI Seah, Ivan/0000-0001-7843-1917; Hunziker, Walter/0000-0002-5265-4933;
   Loh, Xian Jun/0000-0001-8118-6502; Liu, Zengping/0000-0002-2578-293X;
   Lingam, Gopal/0000-0001-9130-5712
FU IAF-PP (HMBS Domain) [H17/01/a0/013]
FX This study was supported by an IAF-PP (HMBS Domain) grant H17/01/a0/013
   (OrBID): OculaR Biomaterials and Device.
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NR 107
TC 40
Z9 41
U1 5
U2 30
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 AUG
PY 2020
VL 34
IS 8
BP 1341
EP 1356
DI 10.1038/s41433-020-0770-y
EA JAN 2020
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MO4WR
UT WOS:000510326900002
PM 32001821
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Millan-Linares, MC
   Toscano, R
   Lemus-Conejo, A
   Martin, ME
   Pedroche, J
   Millan, F
   Montserrat-de la Paz, S
AF Millan-Linares, Maria C.
   Toscano, Rocio
   Lemus-Conejo, Ana
   Martin, Maria E.
   Pedroche, Justo
   Millan, Francisco
   Montserrat-de la Paz, Sergio
TI GPETAFLR, a biopeptide from Lupinus angustifolius L., protects against
   oxidative and inflammatory damage in retinal pigment epithelium cells
SO JOURNAL OF FOOD BIOCHEMISTRY
LA English
DT Article
DE age-related macular degeneration; biopeptide; lupine seeds; Lupinus
   angustifolius; retinal pigment epithelium
ID DIETARY FATTY-ACIDS; EXPRESSION; METABOLITES
AB GPETAFLR, an octapeptide released from the enzymatic hydrolysis of lupine (Lupinus angustifolius L.) protein, has demonstrated anti-inflammatory effect in myeloid lineage. This work aims to evaluate in retinal pigment epithelium (RPE) cells the protective role of GPETAFLR on both oxidative and inflammatory markers known to be involved in age-related macular degeneration (AMD). In comparison with stimulated control cells, GPETAFLR increased glutathione production and diminished the secretion and gene expression of VEFG, IL-1 beta, IL-6, IFN gamma, and TNF-alpha, as well as reactive oxygen species, and nitrite output. Our findings reveal that GPETAFLR, a novel plant peptide, is able to protect against RPE oxidative stress and inflammation. Taken together, these results strongly support innovative nutritional strategies considering Lupinus angustifolius L. as source of proteins to prevent the onset and progression of AMD. Practical applications We reveal a novel nutraceutical impact of GPETAFLR peptide in human RPE cells to prevent oxidative and inflammatory mediators. Our results support that the intake of Lupine angustifolius L., proposed to be a reservoir of GPETAFLR, could lessen the functional decay of RPE cells, leading therefore to a slowdown of the progress of AMD during age. Not only this work, but also future simple clinical studies should raise new nutritional strategies focused on understanding the etiological role of the foods, nutrition, and metabolism in the pathogenesis of ocular disorders.
C1 [Millan-Linares, Maria C.] CSIC, Inst Grasa, Cell Biol Unit, Seville, Spain.
   [Toscano, Rocio; Lemus-Conejo, Ana; Pedroche, Justo; Millan, Francisco] CSIC, Inst Grasa, Dept Food & Hlth, Seville, Spain.
   [Toscano, Rocio; Lemus-Conejo, Ana; Montserrat-de la Paz, Sergio] Univ Seville, Sch Med, Dept Med Biochem Mol Biol & Immunol, Av Dr Fedriani 3, Seville 41071, Spain.
   [Martin, Maria E.] Univ Seville, Fac Biol, Dept Cell Biol, Seville, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto
   de la Grasa (IG); Consejo Superior de Investigaciones Cientificas
   (CSIC); CSIC - Instituto de la Grasa (IG); University of Sevilla;
   University of Sevilla
RP Montserrat-de la Paz, S (通讯作者)，Univ Seville, Sch Med, Dept Med Biochem Mol Biol & Immunol, Av Dr Fedriani 3, Seville 41071, Spain.
EM delapaz@us.es
RI Conejo, Ana Lemus/AAB-5962-2019; Pedroche, Justo/AAG-5713-2020; Martín,
   María/ACU-3685-2022; Martín, María/HDL-9512-2022; Millán-Linares, Maria
   C./W-1924-2018
OI Conejo, Ana Lemus/0000-0002-5539-2393; Martín,
   María/0000-0002-3204-1726; Millán-Linares, Maria C./0000-0002-5661-8366;
   Toscano-Sanchez, Rocio/0000-0002-1913-2711
FU Spanish Ministry of Economy and Competitiveness [AGL2012-40247-C02-01];
   "V Own Research Plan" (University of Seville)
FX This work was supported by grant AGL2012-40247-C02-01 from the Spanish
   Ministry of Economy and Competitiveness. Authors thank Cell Biology Unit
   of Instituto de la Grasa for its assistance during the fulfilment of
   this work and Research Scientist Enrique Martinez Force for his help
   with the protein structure models. SMP acknowledges financial support
   from "V Own Research Plan" (University of Seville).
CR Bienert S, 2017, NUCLEIC ACIDS RES, V45, pD313, DOI 10.1093/nar/gkw1132
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NR 23
TC 5
Z9 5
U1 0
U2 7
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-8884
EI 1745-4514
J9 J FOOD BIOCHEM
JI J. Food Biochem.
PD NOV
PY 2019
VL 43
IS 11
AR e12995
DI 10.1111/jfbc.12995
EA JUL 2019
PG 7
WC Biochemistry & Molecular Biology; Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Food Science & Technology
GA JH9IL
UT WOS:000478700200001
PM 31659814
OA Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Baksheeva, VE
   Tiulina, VV
   Tikhomirova, NK
   Gancharova, OS
   Komarov, SV
   Philippov, PP
   Zamyatnin, AA
   Senin, II
   Zernii, EY
AF Baksheeva, Viktoriia E.
   Tiulina, Veronika V.
   Tikhomirova, Natalia K.
   Gancharova, Olga S.
   Komarov, Sergey V.
   Philippov, Pavel P.
   Zamyatnin, Andrey A., Jr.
   Senin, Ivan I.
   Zernii, Evgeni Yu.
TI Suppression of Light-Induced Oxidative Stress in the Retina by
   Mitochondria-Targeted Antioxidant
SO ANTIOXIDANTS
LA English
DT Article
DE light-induced retinal damage; age-related macular degeneration;
   oxidative stress; antioxidant activity; superoxide dismutase;
   glutathione peroxidase; mitochondria-targeted antioxidant; SkQ1; visual
   arrestin; disulfide dimerization of proteins
ID PIGMENT EPITHELIAL-CELLS; VISOMITIN EYE DROPS; BLUE-LIGHT; PLASTOQUINONE
   DERIVATIVES; SUPEROXIDE-DISMUTASE; INTERRUPT EXECUTION; OUTER SEGMENTS;
   MOUSE MODEL; DNA DAMAGE; SUSCEPTIBILITY
AB Light-induced oxidation of lipids and proteins provokes retinal injuries and results in progression of degenerative retinal diseases, such as, for instance, iatrogenic photic maculopathies. Having accumulated over years retinal injuries contribute to development of age-related macular degeneration (AMD). Antioxidant treatment is regarded as a promising approach to protecting the retina from light damage and AMD. Here, we examine oxidative processes induced in rabbit retina by excessive light illumination with or without premedication using mitochondria-targeted antioxidant SkQ1 (10-(6'-plastoquinonyl)decyltriphenyl-phosphonium). The retinal extracts obtained from animals euthanized within 1-7 days post exposure were analyzed for H2O2, malondialdehyde (MDA), total antioxidant activity (AOA), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) using colorimetric and luminescence assays. Oxidation of visual arrestin was monitored by immunoblotting. The light exposure induced lipid peroxidation and H2O2 accumulation in the retinal cells. Unexpectedly, it prominently upregulated AOA in retinal extracts although SOD and GPx activities were compromised. These alterations were accompanied by accumulation of disulfide dimers of arrestin revealing oxidative stress in the photoreceptors. Premedication of the eyes with SkQ1 accelerated normalization of H2O2 levels and redox-status of lipids and proteins, contemporarily enhancing AOA and, likely, sustaining normal activity of GPx. Thus, SkQ1 protects the retina from light-induced oxidative stress and could be employed to suppress oxidative damage of proteins and lipids contributing to AMD.
C1 [Baksheeva, Viktoriia E.; Tiulina, Veronika V.; Tikhomirova, Natalia K.; Gancharova, Olga S.; Philippov, Pavel P.; Zamyatnin, Andrey A., Jr.; Senin, Ivan I.; Zernii, Evgeni Yu.] Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow 119992, Russia.
   [Gancharova, Olga S.] Sechenov First Moscow State Med Univ, Inst Regenerat Med, Moscow 119991, Russia.
   [Komarov, Sergey V.] Skryabin Moscow State Acad Vet Med & Biotechnol, Dept Biol & Pathol Domest Lab & Exot Anim, Moscow 109472, Russia.
   [Zamyatnin, Andrey A., Jr.; Zernii, Evgeni Yu.] Sechenov First Moscow State Med Univ, Inst Mol Med, Moscow 119991, Russia.
C3 Lomonosov Moscow State University; Sechenov First Moscow State Medical
   University; Moscow State Academy of Veterinary Medicine & Biotechnology
   named after K.I. Skryabin; Sechenov First Moscow State Medical
   University
RP Zernii, EY (通讯作者)，Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow 119992, Russia.; Zernii, EY (通讯作者)，Sechenov First Moscow State Med Univ, Inst Mol Med, Moscow 119991, Russia.
EM vbaksheeva@belozersky.msu.ru; tyulina_nika@list.ru;
   tikhomir@belozersky.msu.ru; olgancharova@belozersky.msu.ru;
   skomarov1977@mail.ru; ppph@belozersky.msu.ru; zamyat@genebee.msu.ru;
   senin@belozersky.msu.ru; zerni@belozersky.msu.ru
RI Viktoriia, Baksheeva E/Q-8035-2018; Gancharova, Olga S/M-9980-2014;
   Zamyatnin, Andrey A./D-6443-2012; Zernii, Evgeni Yu./D-9446-2012;
   Baksheeva, Viktoriia/AAO-3153-2020
OI Gancharova, Olga S/0000-0001-7441-1062; Zamyatnin, Andrey
   A./0000-0002-3046-4565; Zernii, Evgeni Yu./0000-0002-3013-7863;
   Baksheeva, Viktoriia/0000-0002-0445-2667
FU RUSSIAN SCIENCE FOUNDATION [16-15-00255]
FX This research was funded by the RUSSIAN SCIENCE FOUNDATION, grant number
   16-15-00255.
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NR 72
TC 21
Z9 22
U1 0
U2 7
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD JAN
PY 2019
VL 8
IS 1
AR 3
DI 10.3390/antiox8010003
PG 17
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 HJ8HR
UT WOS:000457439300003
PM 30577635
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, YK
   Grenell, A
   Zhong, FY
   Yam, M
   Hauer, A
   Gregor, E
   Zhu, SY
   Lohner, D
   Zhu, JJ
   Du, JH
AF Wang, Yekai
   Grenell, Allison
   Zhong, Fanyi
   Yam, Michelle
   Hauer, Allison
   Gregor, Elizabeth
   Zhu, Siyan
   Lohner, Daniel
   Zhu, Jiangjiang
   Du, Jianhai
TI Metabolic signature of the aging eye in mice
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Metabolite; Aging; Retina; RPE; Lens; Cornea; Optic nerve
ID NICOTINAMIDE N-METHYLTRANSFERASE; SPECTROMETRY-BASED METABOLOMICS;
   PIGMENT EPITHELIAL-CELLS; AGE-RELATED-CHANGES; MITOCHONDRIAL
   DYSFUNCTION; OXIDATIVE STRESS; BRUCHS MEMBRANE; OPTIC-NERVE; LENS;
   TAURINE
AB Aging is a major risk factor for age-related ocular diseases including age-related macular degeneration in the retina and retinal pigment epithelium (RPE), cataracts in the lens, glaucoma in the optic nerve, and dry eye syndrome in the cornea. We used targeted metabolomics to analyze metabolites from young (6 weeks) and old (73 weeks) eyes in C57 BL6/J mice. Old mice had diminished electroretinogram responses and decreased number of photoreceptors in their retinas. Among the 297 detected metabolites, 45-114 metabolites are significantly altered in aged eye tissues, mostly in the neuronal tissues (retina and optic nerve) and less in cornea, RPE/choroid, and lens. We noted that changes of metabolites in mitochondrial metabolism and glucose metabolism are common features in the aged retina, RPE/choroid, and optic nerve. The aging retina, cornea, and optic nerve also share similar changes in Nicotinamide adenine dinucleotide (NAD), 1-methylnicotinamides, 3-methylhistidine, and other methylated metabolites. Metabolites in taurine metabolism are strikingly influenced by aging in the cornea and lens. In conclusion, the aging eye has both common and tissue-specific metabolic signatures. These changes may be attributed to dysregulated mitochondrial metabolism, reprogrammed glucose metabolism and impaired methylation in the aging eye. Our findings provide biochemical insights into the mechanisms of age-related ocular changes. (C) 2018 Elsevier Inc. All rights reserved.
C1 [Wang, Yekai; Grenell, Allison; Yam, Michelle; Hauer, Allison; Gregor, Elizabeth; Zhu, Siyan; Lohner, Daniel; Du, Jianhai] West Virginia Univ, Dept Ophthalmol, Morgantown, WV 26506 USA.
   [Wang, Yekai; Grenell, Allison; Yam, Michelle; Hauer, Allison; Gregor, Elizabeth; Zhu, Siyan; Lohner, Daniel; Du, Jianhai] West Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA.
   [Zhong, Fanyi; Zhu, Jiangjiang] Miami Univ, Dept Chem & Biochem, Oxford, OH 45056 USA.
C3 West Virginia University; West Virginia University; University System of
   Ohio; Miami University
RP Du, JH (通讯作者)，West Virginia Univ, Eye Inst, One Med Ctr,POB 9193, Morgantown, WV 26505 USA.
EM jianhai.du@wvumedicine.org
OI GRENELL, ALLISON/0000-0002-1463-849X; Yam, Michelle/0000-0001-5250-994X
FU NIH [EY026030]; Brightfocus Foundation; NATIONAL EYE INSTITUTE
   [R01EY026030] Funding Source: NIH RePORTER
FX This work was supported by NIH Grants EY026030 (to J.D., and Jennifer
   Chao.) and the Brightfocus Foundation (to J.D. and Jennifer Chao). We
   thank Dr James Hurley for helpful comments and suggestions.
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NR 69
TC 34
Z9 34
U1 1
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD NOV
PY 2018
VL 71
BP 223
EP 233
DI 10.1016/j.neurobiolaging.2018.07.024
PG 11
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA GU7QY
UT WOS:000445521400021
PM 30172221
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Hussain, MA
   Bhuiyan, A
   Luu, CD
   Smith, RT
   Guymer, RH
   Ishikawa, H
   Schuman, JS
   Ramamohanarao, K
AF Hussain, Md Akter
   Bhuiyan, Alauddin
   Luu, Chi D.
   Smith, R. Theodore
   Guymer, Robyn H.
   Ishikawa, Hiroshi
   Schuman, Joel S.
   Ramamohanarao, Kotagiri
TI Classification of healthy and diseased retina using SD-OCT imaging and
   Random Forest algorithm
SO PLOS ONE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; CHOROIDAL THICKNESS;
   IMAGES; IDENTIFICATION; DIAGNOSIS
AB In this paper, we propose a novel classification model for automatically identifying individuals with age-related macular degeneration (AMD) or Diabetic Macular Edema (DME) using retinal features from Spectral Domain Optical Coherence Tomography (SD-OCT) images. Our classification method uses retinal features such as the thickness of the retina and the thickness of the individual retinal layers, and the volume of the pathologies such as drusen and hyper-reflective intra-retinal spots. We extract automatically, ten clinically important retinal features by segmenting individual SD-OCT images for classification purposes. The effectiveness of the extracted features is evaluated using several classification methods such as Random Forrest on 251 (59 normal, 177 AMD and 15 DME) subjects. We have performed 15-fold cross-validation tests for three phenotypes; DME, AMD and normal cases using these data sets and achieved accuracy of more than 95% on each data set with the classification method using Random Forrest. When we trained the system as a two-class problem of normal and eye with pathology, using the Random Forrest classifier, we obtained an accuracy of more than 96%. The area under the receiver operating characteristic curve (AUC) finds a value of 0.99 for each dataset. We have also shown the performance of four state-of-the-methods for classification the eye participants and found that our proposed method showed the best accuracy.
C1 [Hussain, Md Akter; Ramamohanarao, Kotagiri] Univ Melbourne, Comp & Informat Syst, Melbourne, Vic, Australia.
   [Hussain, Md Akter; Bhuiyan, Alauddin] iHealthScreen Inc, Queens, NY 11367 USA.
   [Luu, Chi D.; Guymer, Robyn H.] Univ Melbourne, Dept Surg Ophthalmol, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Smith, R. Theodore] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
   [Ishikawa, Hiroshi; Schuman, Joel S.] NYU, Sch Med, New York, NY USA.
C3 University of Melbourne; Centre for Eye Research Australia; Royal
   Victorian Eye & Ear Hospital; University of Melbourne; Icahn School of
   Medicine at Mount Sinai; New York University
RP Hussain, MA (通讯作者)，Univ Melbourne, Comp & Informat Syst, Melbourne, Vic, Australia.; Hussain, MA (通讯作者)，iHealthScreen Inc, Queens, NY 11367 USA.
EM hussain@student.unimelb.edu.au
RI Schuman, Joel S/M-2389-2019; Ishikawa, Hiroshi/ABC-6293-2020; Schuman,
   Joel S/K-7304-2012
OI Schuman, Joel S/0000-0002-8885-3766; Ishikawa,
   Hiroshi/0000-0001-6310-5748; Schuman, Joel S/0000-0002-8885-3766;
   Guymer, Robyn/0000-0002-9441-4356; Hussain, Md Akter/0000-0002-7780-298X
FU University of Melbourne International PhD Research Scholarship;
   Principal Research Fellowship [1103013]; Australian Research Council
   (ARC) [DP110102621]
FX This research is funded by three funds. M.A. Hussain is supported by the
   University of Melbourne International PhD Research Scholarship. R.H.
   Guymer is supported by Principal Research Fellowship (1103013). K.
   Ramamohanarao is supported by Australian Research Council (ARC
   DP110102621).
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NR 25
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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 JUN 4
PY 2018
VL 13
IS 6
AR e0198281
DI 10.1371/journal.pone.0198281
PG 17
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GI0YU
UT WOS:000434097100026
PM 29864167
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Zheng, YJ
   Wu, XH
   Lin, XM
   Lin, HT
AF Zheng, Yajing
   Wu, Xiaohang
   Lin, Xiaoming
   Lin, Haotian
TI The Prevalence of Depression and Depressive Symptoms among Eye Disease
   Patients: A Systematic Review and Meta-analysis
SO SCIENTIFIC REPORTS
LA English
DT Article
ID QUALITY-OF-LIFE; CROSS-SECTIONAL ANALYSIS; MACULAR DEGENERATION;
   HOSPITAL ANXIETY; GLOBAL BURDEN; OLDER-PEOPLE; VISION LOSS; AGE;
   GLAUCOMA; VALIDITY
AB The prevalence of depression among different eye disease patients varies across studies and has not been systematically reviewed. This study is to provide a summary of the prevalence of depression among eye disease patients. PubMed, Medline, Embase and Cochrane Library were searched from January, 1990 to December, 2015 to identify studies with information on the prevalence of depression among ophthalmic patients. A random/fixed-effects meta-analysis was used to estimate the pooled prevalence of depression among eye disease patients. Heterogeneity was assessed with the I-2 test. 28 studies were selected from 3162 references. The overall pooled prevalence of depression or depressive symptoms with eye disease was 25% (1502/6589 individuals, 95% CI, 0.20-0.30) ranging from 5.4% to 57.0%. Regarding different disease categories, the highest prevalence was revealed for dry eye disease (DED) with 29%, followed by 25% for glaucoma patients, 24% for age-related macular degeneration (AMD) patients, 23% for cataract patients. The increased pooled prevalence of depression was identified in those with eye diseases compared with healthy controls (OR, 1.59; 95% CI, 1.40-1.81; I-2 = 68.5%). Substantial heterogeneity was identified across most estimates (I-2 > 75%). Further research is needed to identify effective strategies for preventing and treating depression among eye disease patients.
C1 [Zheng, Yajing; Wu, Xiaohang; Lin, Xiaoming; Lin, Haotian] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
C3 Sun Yat Sen University
RP Lin, XM; Lin, HT (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
EM linxiaom@mail.sysu.edu.cn; haot.lin@hotmail.com
OI Lin, Haotian/0000-0003-4672-9721; lin, xiao ming/0000-0001-7161-1085
FU Key Research Plan for the National Natural Science Foundation of China
   in Cultivation Project [91546101]; Pear River Scholar Program of
   Guangdong Province; Outstanding Young Teacher Cultivation Projects in
   Guangdong Province [YQ2015006]; Guangdong Provincial Natural Science
   Foundation for Distinguished Young Scholars of China [2014A030306030];
   Youth Science and Technology Innovation Talents Funds in a Special
   Support Plan for High Level Talents in Guangdong Province
   [2014TQ01R573]; Young Teacher Top-Support project of Sun Yat-sen
   University [2015ykzd11]
FX This study was supported by the Key Research Plan for the National
   Natural Science Foundation of China in Cultivation Project (No.
   91546101), the Pear River Scholar Program of Guangdong Province (Haotian
   Lin), the Outstanding Young Teacher Cultivation Projects in Guangdong
   Province (No. YQ2015006), the Guangdong Provincial Natural Science
   Foundation for Distinguished Young Scholars of China (No.
   2014A030306030), the Youth Science and Technology Innovation Talents
   Funds in a Special Support Plan for High Level Talents in Guangdong
   Province (No. 2014TQ01R573) and the Young Teacher Top-Support project of
   Sun Yat-sen University (No. 2015ykzd11). The sponsor or funding
   organization had no role in the design or conduct of this research.
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NR 61
TC 71
Z9 72
U1 2
U2 23
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 12
PY 2017
VL 7
AR 46453
DI 10.1038/srep46453
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Science & Technology - Other Topics
GA ER7LB
UT WOS:000398993200002
PM 28401923
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Chen, CL
   Wang, RK
AF Chen, Chieh-Li
   Wang, Ruikang K.
TI Optical coherence tomography based angiography [Invited]
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Review
ID RETINAL VEIN OCCLUSION; AMPLITUDE-DECORRELATION ANGIOGRAPHY; MACULAR
   TELANGIECTASIA TYPE-2; SWEPT-SOURCE OCT; FLOW VELOCITY ESTIMATION;
   CEREBRAL-BLOOD-FLOW; IN-VIVO; SPECTRAL-DOMAIN; HUMAN SKIN;
   MICRO-ANGIOGRAPHY
AB Optical coherence tomography (OCT)-based angiography (OCTA) provides in vivo, three-dimensional vascular information by the use of flowing red blood cells as intrinsic contrast agents, enabling the visualization of functional vessel networks within microcirculatory tissue beds non-invasively, without a need of dye injection. Because of these attributes, OCTA has been rapidly translated to clinical ophthalmology within a short period of time in the development. Various OCTA algorithms have been developed to detect the functional micro-vasculatures in vivo by utilizing different components of OCT signals, including phase-signal-based OCTA, intensity-signal-based OCTA and complex-signal-based OCTA. All these algorithms have shown, in one way or another, their clinical values in revealing micro-vasculatures in biological tissues in vivo, identifying abnormal vascular networks or vessel impairment zones in retinal and skin pathologies, detecting vessel patterns and angiogenesis in eyes with age-related macular degeneration and in skin and brain with tumors, and monitoring responses to hypoxia in the brain tissue. The purpose of this paper is to provide a technical oriented overview of the OCTA developments and their potential preclinical and clinical applications, and to shed some lights on its future perspectives. Because of its clinical translation to ophthalmology, this review intentionally places a slightly more weight on ophthalmic OCT angiography. (C) 2017 Optical Society of America
C1 [Chen, Chieh-Li; Wang, Ruikang K.] Univ Washington, Dept Bioengn, 3720 15th Ave NE, Seattle, WA 98195 USA.
   [Chen, Chieh-Li; Wang, Ruikang K.] Univ Washington, Dept Ophthalmol, 325 9th Ave, Seattle, WA 98104 USA.
C3 University of Washington; University of Washington Seattle; University
   of Washington; University of Washington Seattle
RP Wang, RK (通讯作者)，Univ Washington, Dept Bioengn, 3720 15th Ave NE, Seattle, WA 98195 USA.; Wang, RK (通讯作者)，Univ Washington, Dept Ophthalmol, 325 9th Ave, Seattle, WA 98104 USA.
EM wangrk@uw.edu
RI Wang, Ruikang/L-3889-2019
OI Wang, Ruikang/0000-0001-5169-8822
FU National Institutes of Health [NEI R01-EY024158, NHLBI R01-HL093140];
   Carl Zeiss Meditec Inc.
FX National Institutes of Health contracts NEI R01-EY024158 and NHLBI
   R01-HL093140, and Carl Zeiss Meditec Inc.
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NR 155
TC 250
Z9 258
U1 17
U2 83
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 2017
VL 8
IS 2
BP 1056
EP 1082
DI 10.1364/BOE.8.001056
PG 27
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 EK8OA
UT WOS:000394182100043
PM 28271003
OA Green Published, gold, Green Submitted
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Lancon, A
   Frazzi, R
   Latruffe, N
AF Lancon, Allan
   Frazzi, Raffaele
   Latruffe, Norbert
TI Anti-Oxidant, Anti-Inflammatory and Anti-Angiogenic Properties of
   Resveratrol in Ocular Diseases
SO MOLECULES
LA English
DT Review
DE resveratrol; eyes; inflammation
ID PIGMENT EPITHELIAL-CELLS; NF-KAPPA-B; OXIDATIVE STRESS; MACULAR
   DEGENERATION; TRANS-RESVERATROL; IN-VIVO; INFLAMMATION; INHIBITION;
   EXPRESSION; SUPPRESSION
AB Resveratrol (3,4,5 trihydroxy-trans-stilbene) is one of the best known phytophenols with pleiotropic properties. It is a phytoalexin produced by vine and it leads to the stimulation of natural plant defenses but also exhibits many beneficial effects in animals and humans by acting on a wide range of organs and tissues. These include the prevention of cardiovascular diseases, anti-cancer potential, neuroprotective effects, homeostasia maintenance, aging delay and a decrease in inflammation. Age-related macular degeneration (AMD) is one of the main causes of deterioration of vision in adults in developed countries This review deals with resveratrol and ophthalmology by focusing on the antioxidant, anti-inflammatory, and anti-angiogenic effects of this molecule. The literature reports that resveratrol is able to act on various cell types of the eye by increasing the level of natural antioxidant enzymatic and molecular defenses. Resveratrol anti-inflammatory effects are due to its capacity to limit the expression of pro-inflammatory factors, such as interleukins and prostaglandins, and also to decrease the chemo-attraction and recruitment of immune cells to the inflammatory site. In addition to this, resveratrol was shown to possess anti-VEGF effects and to inhibit the proliferation and migration of vascular endothelial cells. Resveratrol has the potential to be used in a range of human ocular diseases and conditions, based on animal models and in vitro experiments.
C1 [Lancon, Allan; Latruffe, Norbert] Univ Bourgogne, Fac Sci SVTE, Lab BioperoxIL, 6 Bd Gabriel, F-21000 Dijon, France.
   [Frazzi, Raffaele] Arcispedale S Maria Nuova IRCCS, Lab Translat Res, I-42123 Reggio Emilia, Italy.
C3 Universite de Bourgogne; IRCCS Arcispedale S. Maria Nuova
RP Latruffe, N (通讯作者)，Univ Bourgogne, Fac Sci SVTE, Lab BioperoxIL, 6 Bd Gabriel, F-21000 Dijon, France.
EM allan.lancon@gmail.com; raffaele.frazzi@asmn.re.it;
   latruffe@u-bourgogne.fr
FU Laboratoires Thea, Clermont Ferrand, France; Gr.A.D.E. foundation Reggio
   Emilia, Italy
FX We thank the Laboratoires Thea, Clermont Ferrand, France, especially M.
   Armel Clerc for their interest and support. We also thank Gr.A.D.E.
   foundation Reggio Emilia, Italy, for the precious support. The English
   language has been kindly checked by Jean-Jacques Michaille, invited
   professor for many years to Ohio State University, Columbus, USA.
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NR 36
TC 83
Z9 86
U1 2
U2 36
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1420-3049
J9 MOLECULES
JI Molecules
PD MAR
PY 2016
VL 21
IS 3
AR 304
DI 10.3390/molecules21030304
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA DI9DR
UT WOS:000373802200071
PM 26950104
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Hernowo, AT
   Prins, D
   Baseler, HA
   Plank, T
   Gouws, AD
   Hooymans, JMM
   Morland, AB
   Greenlee, MW
   Cornelissen, FW
AF Hernowo, Aditya T.
   Prins, Doety
   Baseler, Heidi A.
   Plank, Tina
   Gouws, Andre D.
   Hooymans, Johanna M. M.
   Morland, Antony B.
   Greenlee, Mark W.
   Cornelissen, Frans W.
TI Morphometric analyses of the visual pathways in macular degeneration
SO CORTEX
LA English
DT Article
DE Macular degeneration; Visual pathway; Visual field; Voxel-based
   morphometry
ID AGE-RELATED MACULOPATHY; COGNITIVE IMPAIRMENT; GEOGRAPHIC ATROPHY;
   CORTICAL REORGANIZATION; ALZHEIMERS-DISEASE; FIBER TRACTS; RISK-FACTORS;
   HUMAN BRAIN; PREVALENCE; CORTEX
AB Introduction: Macular degeneration (MD) causes central visual field loss. When field defects occur in both eyes and overlap, parts of the visual pathways are no longer stimulated. Previous reports have shown that this affects the grey matter of the primary visual cortex, but possible effects on the preceding visual pathway structures have not been fully established.
   Methods: In this multicentre study, we used high-resolution anatomical magnetic resonance imaging and voxel-based morphometry to investigate the visual pathway structures up to the primary visual cortex of patients with age-related macular degeneration (AMD) and juvenile macular degeneration (JMD).
   Results: Compared to age-matched healthy controls, in patients with JMD we found volumetric reductions in the optic nerves, the chiasm, the lateral geniculate bodies, the optic radiations and the visual cortex. In patients with AMD we found volumetric reductions in the lateral geniculate bodies, the optic radiations and the visual cortex. An unexpected finding was that AMD, but not JMD, was associated with a reduction in frontal white matter volume.
   Conclusion: MD is associated with degeneration of structures along the visual pathways. A reduction in frontal white matter volume only present in the AMD patients may constitute a neural correlate of previously reported association between AMD and mild cognitive impairment. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Hernowo, Aditya T.; Prins, Doety; Cornelissen, Frans W.] Univ Groningen, Univ Med Ctr Groningen, Lab Expt Ophthalmol, NL-9700 RB Groningen, Netherlands.
   [Hernowo, Aditya T.] Gadjah Mada Univ, Dept Ophthalmol, Yogyakarta, Indonesia.
   [Baseler, Heidi A.; Morland, Antony B.] Univ York, Dept Psychol, York YO10 5DD, N Yorkshire, England.
   [Plank, Tina; Greenlee, Mark W.] Univ Regensburg, Inst Expt Psychol, D-93053 Regensburg, Germany.
   [Baseler, Heidi A.; Gouws, Andre D.; Morland, Antony B.] Hull York Med Sch, Ctr Neurosci, York, N Yorkshire, England.
   [Hooymans, Johanna M. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Ophthalmol, NL-9700 RB Groningen, Netherlands.
C3 University of Groningen; Gadjah Mada University; University of York -
   UK; University of Regensburg; University of Hull; University of York -
   UK; University of Groningen
RP Cornelissen, FW (通讯作者)，Univ Groningen, Univ Med Ctr Groningen, Lab Expt Ophthalmol, POB 30001, NL-9700 RB Groningen, Netherlands.
EM f.w.cornelissen@umcg.nl
RI Greenlee, Mark/M-6414-2018; Hernowo, Aditya/M-9651-2015; Hernowo,
   Aditya/GPK-4884-2022; Baseler, Heidi/AAI-7387-2020; Hernowo,
   Aditya/M-9316-2017
OI Greenlee, Mark/0000-0003-2305-9286; Hernowo, Aditya/0000-0002-9212-6705;
   Baseler, Heidi/0000-0003-0995-8453; Morland, Antony/0000-0002-6754-5545;
   Gouws, Andre/0000-0003-0674-7829; Plank, Tina/0000-0001-5329-7037
FU University of Groningen, The Netherlands; Graduate School of Medical
   Sciences (GSMS); Stichting Nederlands Oogheelkundig Onderzoek (SNOO);
   UitZicht - Stichting MD Fonds; Landelijke Stichting voor Blinden en
   Slechtzienden (LSBS); Algemene Nederlandse Vereniging ter Voorkoming van
   Blindheid (ANVVB); German Research Foundation (DFG) [FOR 1075, TP8]; UK
   Medical Research Council; MRC [G0401339] Funding Source: UKRI; Medical
   Research Council [G0401339] Funding Source: researchfish
FX The first author was supported by the "RuG Fellowship Program" grant
   scheme from the University of Groningen, The Netherlands. The Graduate
   School of Medical Sciences (GSMS) supported the second author. This work
   was further supported by research grants from Stichting Nederlands
   Oogheelkundig Onderzoek (SNOO), Nelly Reef Fund, and - via UitZicht -
   Stichting MD Fonds, Landelijke Stichting voor Blinden en Slechtzienden
   (LSBS), and Algemene Nederlandse Vereniging ter Voorkoming van Blindheid
   (ANVVB) to F.W.C., the German Research Foundation (DFG: Project FOR
   1075, TP8) to T.P. and M.W.G., and the UK Medical Research Council to
   A.B.M. The funding organizations had no role in the design or conduct of
   this research.
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NR 64
TC 49
Z9 49
U1 0
U2 23
PU ELSEVIER MASSON, CORPORATION OFFICE
PI PARIS
PA 65 CAMILLE DESMOULINS CS50083 ISSY-LES-MOULINEAUX, 92442 PARIS, FRANCE
SN 0010-9452
EI 1973-8102
J9 CORTEX
JI Cortex
PD JUL
PY 2014
VL 56
SI SI
BP 99
EP 110
DI 10.1016/j.cortex.2013.01.003
PG 12
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA AL4TY
UT WOS:000339128900010
PM 23453791
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Hsu, MY
   Yang, CY
   Hsu, WH
   Lin, KH
   Wang, CY
   Shen, YC
   Chen, YC
   Chau, SF
   Tsai, HY
   Cheng, CM
AF Hsu, Min-Yen
   Yang, Chung-Yao
   Hsu, Wen-Hsin
   Lin, Keng-Hung
   Wang, Chun-Yuan
   Shen, Ying-Cheng
   Chen, Yu-Chen
   Chau, Siu-Fung
   Tsai, Hin-Yeung
   Cheng, Chao-Min
TI Monitoring the VEGF level in 'aqueous humor of patients with
   ophthalmologically relevant diseases via ultrahigh sensitive paper-based
   ELISA
SO BIOMATERIALS
LA English
DT Article
DE Paper-based ELISA; VEGF; Diagnosis; Ophthalmology; Diabetic disease
ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL INJECTION; RANIBIZUMAB;
   BEVACIZUMAB; DEVICES; EYES
AB The vascular endothelial growth factor (VEGF) level in aqueous humor has been used as an indicator to monitor specific diseases in the retinal ischemic condition. For clinical diagnosis, only about 200 mu L of aqueous humor can be collected from the anterior chamber before the threat of anterior chamber collapse. It is necessary to develop an inexpensive diagnostic approach with the characteristics of highly sensitive, short operation duration, and requires small clinical sample quantities. To achieve the main objective of this study, we first prepared bevacizumab to be conjugated with HRP. We then deposited 2 pi aqueous humor from patients with different diseases onto each test zone of paper-based 96-well plates. After the colorimetric results were performed via ELISA protocol, the output signals were recorded using a commercial desktop scanner for analysis. In this study, only 2 pL from the aqueous humor of each patient was required for paper-based ELISA. The mean aqueous VEGF level was 14.4 pg/mL from thirteen patients (N = 13) with senile cataract as the control. However, the mean aqueous VEGF level from other patients with proliferative diabetic retinopathy (N = 14), age-related macular degeneration (N = 17), and retinal vein occlusion (N = 10) showed VEGF increases to 740.1 pg/mL, 383 pg/mL, and 219.4 pg/mL, respectively. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Hsu, Min-Yen; Lin, Keng-Hung; Wang, Chun-Yuan; Shen, Ying-Cheng; Chen, Yu-Chen] Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung 40705, Taiwan.
   [Hsu, Min-Yen; Yang, Chung-Yao; Cheng, Chao-Min] Natl Tsing Hua Univ, Inst Nanoengn & Microsyst, Hsinchu 30013, Taiwan.
   [Hsu, Wen-Hsin] Natl Chung Hsing Univ, Inst Nanosci, Taichung 40227, Taiwan.
   [Chau, Siu-Fung; Tsai, Hin-Yeung] Taichung Tzu Chi Hosp, Dept Ophthalmol, Taichung 42743, Taiwan.
   [Cheng, Chao-Min] Acad Sinica, Inst Cellular & Organism Biol, Taipei 11529, Taiwan.
C3 Taichung Veterans General Hospital; National Tsing Hua University;
   National Chung Hsing University; Buddhist Tzu Chi General Hospital;
   Taichung Tzu Chi Hospital; Academia Sinica - Taiwan
RP Cheng, CM (通讯作者)，101,Sec 2,Kuang Fu Rd, Hsinchu 30013, Taiwan.
EM chaomin@mx.nthu.edu.tw
RI Hsu, MinYen/AAT-2200-2021
FU National Science Council of Taiwan [NSC 101-2628-E-007-011-MY3, NSC
   102-2221-E-007-031]
FX We would like to thank the National Science Council of Taiwan for
   financially supporting this research under Contract No. NSC
   101-2628-E-007-011-MY3 and NSC 102-2221-E-007-031 (to C.-M. Cheng). The
   procedure in this study has been approved by the Internal Ethical
   Committee of Taichung General Veteran Hospital, Taiwan (IRB No.
   CF11213).
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NR 31
TC 65
Z9 65
U1 1
U2 53
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 APR
PY 2014
VL 35
IS 12
BP 3729
EP 3735
DI 10.1016/j.biomaterials.2014.01.030
PG 7
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA AC3OS
UT WOS:000332431700002
PM 24484673
DA 2022-11-30
ER

PT J
AU Bitner, H
   Mizrahi-Meissonnier, L
   Griefner, G
   Erdinest, I
   Sharon, D
   Banin, E
AF Bitner, Hanna
   Mizrahi-Meissonnier, Liliana
   Griefner, Gabriel
   Erdinest, Inbar
   Sharon, Dror
   Banin, Eyal
TI A Homozygous Frameshift Mutation in BEST1 Causes the Classical Form of
   Best Disease in an Autosomal Recessive Mode
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID VITELLIFORM MACULAR DYSTROPHY; OPTICAL COHERENCE TOMOGRAPHY; BESTROPHIN
   GENE-MUTATIONS; RETINITIS-PIGMENTOSA; VMD2 GENE; DEGENERATION;
   RETINOPATHY; FAMILY
AB PURPOSE. Best disease is a monogenic macular degeneration caused mainly by heterozygous mutations in the BEST1 gene. The objective was to characterize the molecular and clinical features of patients with the classical form of Best disease that is inherited in an autosomal recessive mode.
   METHODS. Clinical evaluation included detailed family history, a full ophthalmologic examination, electro-oculography (EOG), electroretinography, color vision testing, and ocular imaging. Mutation analysis was performed by direct sequencing of PCR products.
   RESULTS. Two young siblings affected by Best disease, as confirmed by funduscopy, retinal imaging, and electrophysiologic assessment, were recruited for the study. Molecular analysis revealed a novel homozygous deletion (c.1415delT) in the BEST1 gene leading to a frameshift followed by a premature stop codon, which cosegregated with the disease in a recessive mode. The heterozygous parents had normal visual acuity, retinal appearance, and function. The two heterozygous grandmothers, ages 61 and 62, also had normal Arden ratios on EOG, but one of them manifested moderate-to-severe dry non-neovascular age-related macular degeneration.
   CONCLUSIONS. We show here that the typical vitelliform phenotype of Best disease, usually transmitted in an autosomal dominant fashion, can be inherited as an autosomal recessive disease due to homozygosity for a frameshift mutation. (Invest Ophthalmol Vis Sci. 2011; 52:5332-5338) DOI: 10.1167/iovs.11.7174
C1 [Bitner, Hanna; Mizrahi-Meissonnier, Liliana; Griefner, Gabriel; Erdinest, Inbar; Sharon, Dror; Banin, Eyal] Hadassah Hebrew Univ, Dept Ophthalmol, Med Ctr, Jerusalem, Israel.
C3 Hebrew University of Jerusalem; Hadassah University Medical Center
RP Sharon, D (通讯作者)，Hadassah Hebrew Univ, Dept Ophthalmol, Med Ctr, Jerusalem, Israel.
EM dror.sharon1@gmail.com; banine@cc.huji.ac.il
RI Sharon, Dror/P-4539-2015
OI Sharon, Dror/0000-0002-1789-5811
FU Chief Scientist Office of the Israeli Ministry of Health [3000003241];
   Yedidut 1 Research Grant
FX Supported in part by Grant No. 3000003241 from the Chief Scientist
   Office of the Israeli Ministry of Health and by the Yedidut 1 Research
   Grant.
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NR 31
TC 35
Z9 35
U1 0
U2 1
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 5332
EP 5338
DI 10.1167/iovs.11-7174
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800QC
UT WOS:000293377400043
PM 21467170
DA 2022-11-30
ER

PT J
AU Lumbroso, B
   Savastano, MC
   Rispoli, M
   Balestrazzi, A
   Savastano, A
   Balestrazzi, E
AF Lumbroso, Bruno
   Savastano, Maria Cristina
   Rispoli, Marco
   Balestrazzi, Angelo
   Savastano, Alfonso
   Balestrazzi, Emilio
TI MORPHOLOGIC DIFFERENCES, ACCORDING TO ETIOLOGY, IN PIGMENT EPITHELIAL
   DETACHMENTS BY MEANS OF EN FACE OPTICAL COHERENCE TOMOGRAPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; central serous chorioretinopathy; en
   face optical coherence tomography; pigment epithelial detachment
ID CENTRAL SEROUS CHORIORETINOPATHY; FLUORESCEIN ANGIOGRAPHY; MACULAR
   DEGENERATION; PREGNANCY; ARTIFACTS; RETINA; SAFETY
AB Purpose: To assess morphologic differences in pigment epithelial detachment (PED) with en face optical coherence tomography in central serous chorioretinopathy (CSC) and age-related macular degeneration (AMD).
   Methods: We recruited 30 eyes of 22 patients with PED. Nine eyes had a clinical diagnosis of CSC and 21 had AMD. All patients were assessed with en face optical coherence tomography. Morphologic PED aspects were estimated on C-scans and classified according to shape, inner silhouette, content, wall aspects, wall thickness, and size.
   Results: Pigment epithelial detachment shape was predominantly circular (88.8%) in CSC and irregular or with multilobular features in AMD (76.2%). The PED inner silhouette had a smooth aspect (88.9%) in CSC and a slightly granular aspect or granular profile in AMD (100%). Clear PED content was the most characteristic feature of CSC (88.9%) but not of AMD. In CSC, PED morphologic wall aspect was uniform or slightly irregular (100%), while in AMD, it was slightly irregular (52.4%) or irregular (47.6%). Pigment epithelial detachment wall thickness and dimensions were larger in AMD than in CSC. Statistically significant differences were observed between CSC and AMD concerning PED inner silhouette, contents, wall aspects, and wall thickness measurements.
   Conclusion: En face optical coherence tomography scanning is a valuable tool for showing important morphologic differences between CSC and AMD. RETINA 31: 553-558, 2011
C1 [Lumbroso, Bruno] Ctr Oftalmol Mediterraneo, I-00195 Rome, Italy.
   [Savastano, Maria Cristina; Balestrazzi, Emilio] Univ Cattolica Sacro Cuore, Dept Ophthalmol, Policlin A Gemelli, Rome, Italy.
   [Rispoli, Marco] Ophthalmol Hosp, Rome, Italy.
   [Balestrazzi, Angelo] Univ Siena, Dept Ophthalmol, I-53100 Siena, Italy.
   [Savastano, Alfonso] SUN Naples, Inst Ophthalmol, Naples, Italy.
C3 Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli;
   University of Siena; Universita della Campania Vanvitelli
RP Lumbroso, B (通讯作者)，Ctr Oftalmol Mediterraneo, Via A Brofferio 7, I-00195 Rome, Italy.
EM bruno.lumbroso@gmail.com
RI Savastano, Alfonso/AAJ-4173-2021; Savastano, Maria Cristina/I-5355-2015;
   rispoli, marco/N-1054-2016
OI Savastano, Alfonso/0000-0003-1575-6567; Savastano, Maria
   Cristina/0000-0003-1397-4333; rispoli, marco/0000-0003-2689-9002
FU Marco Oradei; Catholic University "SacroCuore, Policlinico A. Gemelli,"
   Rome, Italy; Gaspare Giovinco, "Universita degli Studi di Cassino,"
   Cassino, Italy
FX The authors thank Marco Oradei, Catholic University "SacroCuore,
   Policlinico A. Gemelli," Rome, Italy, and Gaspare Giovinco, "Universita
   degli Studi di Cassino," Cassino, Italy, for their support.
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Z9 21
U1 0
U2 1
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 MAR
PY 2011
VL 31
IS 3
BP 553
EP 558
DI 10.1097/IAE.0b013e3181eef3eb
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 722YW
UT WOS:000287472400018
PM 21343873
DA 2022-11-30
ER

PT J
AU Yu, DY
   Cheung, SH
   Legge, GE
   Chung, STL
AF Yu, Deyue
   Cheung, Sing-Hang
   Legge, Gordon E.
   Chung, Susana T. L.
TI Reading speed in the peripheral visual field of older adults: Does it
   benefit from perceptual learning?
SO VISION RESEARCH
LA English
DT Article
DE Reading; Letter recognition; Peripheral vision; Perceptual learning;
   Aging; Low vision; Visual rehabilitation
ID LETTER-RECOGNITION; DENDRITIC SPINES; PSYCHOPHYSICS; VISION;
   REORGANIZATION; AGE; BOOTSTRAP; SLEEP; DISCRIMINATION; IDENTIFICATION
AB Enhancing reading ability in peripheral vision is important for the rehabilitation of people with central-visual-field loss from age-related macular degeneration (AMD). Previous research has shown that perceptual learning, based on a trigram letter-recognition task, improved peripheral reading speed among normally-sighted young adults (Chung, Legge, & Cheung, 2004). Here we ask whether the same happens in older adults in an age range more typical of the onset of AMD. Eighteen normally-sighted subjects, aged 55-76 years, were randomly assigned to training or control groups. Visual-span profiles (plots of letter-recognition accuracy as a function of horizontal letter position) and RSVP reading speeds were measured at 10 degrees above and below fixation during pre- and post-tests for all subjects. Training consisted of repeated measurements of visual-span profiles at 10 degrees below fixation, in four daily sessions. The control subjects did not receive any training. Perceptual learning enlarged the visual spans in both trained (lower) and untrained (upper) visual fields. Reading speed improved in the trained field by 60% when the trained print size was used. The training benefits for these older subjects were weaker than the training benefits for young adults found by Chung et al. Despite the weaker training benefits, perceptual learning remains a potential option for low-vision reading rehabilitation among older adults. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Yu, Deyue; Cheung, Sing-Hang; Legge, Gordon E.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
   [Yu, Deyue; Chung, Susana T. L.] Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA.
   [Cheung, Sing-Hang] Univ Hong Kong, Dept Psychol, Hong Kong, Hong Kong, Peoples R China.
C3 University of Minnesota System; University of Minnesota Twin Cities;
   University of California System; University of California Berkeley;
   University of Hong Kong
RP Legge, GE (通讯作者)，Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
EM legge@umn.edu
OI Legge, Gordon/0000-0002-3742-1680; Chung, Susana/0000-0003-2729-1808
FU University of Minnesota Doctoral Dissertation Fellowship; NIH [EY002934,
   EY012810]; NATIONAL EYE INSTITUTE [R01EY012810, R01EY002934,
   R37EY002934] Funding Source: NIH RePORTER
FX Preliminary results were presented at the Vision 2005: the 8th
   International Conference on Low Vision Activity and Participation (Yu,
   Cheung, Legge & Chung, 2005 April). The authors thank the dedicated
   subjects for their participation in the study. This research was
   supported by a University of Minnesota Doctoral Dissertation Fellowship
   to S.-H.C., a NIH Grant EY002934 to G.E.L. and a NIH Grant EY012810 to
   S.T.L.C.
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NR 92
TC 43
Z9 45
U1 0
U2 37
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
EI 1878-5646
J9 VISION RES
JI Vision Res.
PD APR 21
PY 2010
VL 50
IS 9
BP 860
EP 869
DI 10.1016/j.visres.2010.02.006
PG 10
WC Neurosciences; Ophthalmology; Psychology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Neurosciences & Neurology; Ophthalmology; Psychology
GA 581IP
UT WOS:000276516200005
PM 20156473
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Jonas, JB
   Xu, L
   Wang, YX
AF Jonas, Jost B.
   Xu, Liang
   Wang, Ya Xing
TI The Beijing Eye Study
SO ACTA OPHTHALMOLOGICA
LA English
DT Review
DE Beijing Eye Study; China; epidemiology; population-based study
ID CENTRAL CORNEAL THICKNESS; AGE-RELATED MACULOPATHY; RURAL ADULT CHINESE;
   ISCHEMIC OPTIC NEUROPATHY; OPEN-ANGLE GLAUCOMA; RETINAL VASCULAR
   ABNORMALITIES; BLUE-MOUNTAINS-EYE; INTRAOCULAR-PRESSURE; VISUAL
   IMPAIRMENT; GENERAL PARAMETERS
AB This review presents and summarizes the findings of the Beijing Eye Study.
   The Beijing Eye Study is a population-based study which included 4439 of 5324 subjects (aged >= 40 years) who were initially examined in 2001. The study was repeated in 2006, when 3251 (73.2% of 4439, or 61.1% of 5324) of the original subjects participated. Participants underwent a series of examinations including: refractometry; pneumotonometry; biomicroscopy assisted by slit-lamp; optical coherence tomography of the anterior segment; photography of the cornea, lens, optic disc, macula and fundus; blood sampling for laboratory tests; blood pressure measurements, and determinations of anthropomorphic parameters. They were also asked to complete a questionnaire which included questions on socioeconomic parameters, and awareness and treatment of ocular and general diseases.
   We present normative data for refractive error, anterior segment measurements, intraocular pressure and optic disc structures and their associations, frequency and causes of visual impairment, blindness and visual field defects, prevalences of trachoma, pterygia, open-angle glaucoma and angle-closure glaucoma, cortical, nuclear and posterior subcapsular cataract, age-related macular degeneration, retinal vein occlusions, diabetes mellitus and diabetic retinopathy, myelinated nerve fibres, and retinitis pigmentosa, and associated and risk factors.
   These data may be helpful for dealing with public health issues in China and for assessing associated and risk factors of ocular and general diseases in general.
C1 [Jonas, Jost B.; Xu, Liang; Wang, Ya Xing] Capital Univ Med Sci, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing 100005, Peoples R China.
   [Jonas, Jost B.] Heidelberg Univ, Dept Ophthalmol, Fac Clin Med Mannheim, D-6800 Mannheim, Germany.
C3 Capital Medical University; Ruprecht Karls University Heidelberg
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 jost.jonas@augen.ma.uni-heidelberg.de
RI wang, YA XING/K-9671-2016
OI wang, YA XING/0000-0003-2749-7793
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NR 104
TC 62
Z9 70
U1 1
U2 13
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 MAY
PY 2009
VL 87
IS 3
BP 247
EP 261
DI 10.1111/j.1755-3768.2008.01385.x
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 434BY
UT WOS:000265251400004
PM 19426355
OA Bronze
DA 2022-11-30
ER

PT J
AU Koskela, A
   Manai, F
   Basagni, F
   Liukkonen, M
   Rosini, M
   Govoni, S
   Dal Monte, M
   Smedowski, A
   Kaarniranta, K
   Amadio, M
AF Koskela, Ali
   Manai, Federico
   Basagni, Filippo
   Liukkonen, Mikko
   Rosini, Michela
   Govoni, Stefano
   Dal Monte, Massimo
   Smedowski, Adrian
   Kaarniranta, Kai
   Amadio, Marialaura
TI Nature-Inspired Hybrids (NIH) Improve Proteostasis by Activating
   Nrf2-Mediated Protective Pathways in Retinal Pigment Epithelial Cells
SO ANTIOXIDANTS
LA English
DT Article
DE autophagy; age-related macular degeneration (AMD); cytoprotection; Nrf2;
   pharmacological modulation; SQSTM1; p62; oxidative stress; retinal
   pigment epithelium (RPE)
ID TRANSCRIPTION FACTOR NRF2; ANTIOXIDANT RESPONSE; MACULAR DEGENERATION;
   AUTOPHAGY; STRESS; TARGET; NFE2L2
AB Antioxidant systems play key roles in many elderly diseases, including age-related macular degeneration (AMD). Oxidative stress, autophagy impairment and inflammation are well-described in AMD, especially in retinal pigment epithelial (RPE) cells. The master regulator of antioxidant defense Nrf2 has been linked to AMD, autophagy and inflammation. In this study, in human ARPE-19 cells, some nature-inspired hybrids (NIH1-3) previously shown to induce Nrf2-mediated protection against oxidative stress were further investigated for their potential against cellular stress caused by dysfunction of protein homeostasis. NIH1-3 compounds increased the expression of two Nrf2-target genes coding defense proteins, HO-1 and SQSTM1/p62, in turn exerting beneficial effects on intracellular redox balance without modification of the autophagy flux. NIH1-3 treatments predisposed ARPE-19 cells to a better response to following exposure to proteasome and autophagy inhibitors, as revealed by the increase in cell survival and decreased secretion of the pro-inflammatory IL-8 compared to NIH-untreated cells. Interestingly, NIH4 compound, through an Nrf2-independent pathway, also increased cell viability and decreased IL-8 secretion, although to a lesser extent than NIH1-3, suggesting that all NIHs are worthy of further investigation into their cytoprotective properties. This study confirms Nrf2 as a valuable pharmacological target in contexts characterized by oxidative stress, such as AMD.
C1 [Koskela, Ali; Liukkonen, Mikko; Kaarniranta, Kai] Univ Eastern Finland, Dept Ophthalmol, Kuopio 70211, Finland.
   [Manai, Federico] Univ Pavia, Dept Biol & Biotechnol L Spallanzani, I-27100 Pavia, Italy.
   [Basagni, Filippo; Rosini, Michela] Univ Bologna, Dept Pharm & Biotechnol, I-40126 Bologna, Italy.
   [Govoni, Stefano; Amadio, Marialaura] Univ Pavia, Dept Drug Sci, Sect Pharmacol, I-27100 Pavia, Italy.
   [Dal Monte, Massimo] Univ Pisa, Dept Biol, I-56126 Pisa, Italy.
   [Dal Monte, Massimo] Univ Pisa, Interdept Res Ctr Nutrafood Nutraceut & Food Hlth, I-56124 Pisa, Italy.
   [Smedowski, Adrian] Med Univ Silesia, Fac Med Sci Katowice, Dept Physiol, PL-40752 Katowice, Poland.
   [Smedowski, Adrian] GlaucoTech Co Ltd, PL-40752 Katowice, Poland.
   [Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, Kuopio 70211, Finland.
C3 University of Eastern Finland; University of Pavia; University of
   Bologna; University of Pavia; University of Pisa; University of Pisa;
   Medical University Silesia; Kuopio University Hospital; University of
   Eastern Finland
RP Amadio, M (通讯作者)，Univ Pavia, Dept Drug Sci, Sect Pharmacol, I-27100 Pavia, Italy.
EM ali.koskela@uef.fi; federico.manai01@universitadipavia.it;
   filippo.basagni2@unibo.it; mikko.liukkonen@uef.fi;
   michela.rosini@unibo.it; govonis@unipv.it; massimo.dalmonte@unipi.it;
   asmedowski@sum.edu.pl; kai.kaarniranta@uef.fi; amadio@unipv.it
RI Basagni, Filippo/GXG-7199-2022; Smedowski, Adrian/ABA-1031-2021; Govoni,
   Stefano/K-2965-2015
OI Basagni, Filippo/0000-0003-0710-4251; Smedowski,
   Adrian/0000-0001-8528-955X; Liukkonen, Mikko/0000-0002-4259-4041;
   ROSINI, MICHELA/0000-0003-3750-2728; Govoni,
   Stefano/0000-0002-7243-6837; Kaarniranta, Kai/0000-0003-2600-8679
FU University of Pavia [1744747]; University of Pavia, Dept. of Drug
   Sciences' Research Funding FRG 2021; University of Bologna; European
   Union [722717]; Academy of Finland [296840, 333302]; Kuopio University
   Hospital VTR grant [5503770]; Sigrid Juselius Foundation; Paivikki and
   Sakari Sohlberg Foundation; Finnish Eye Foundation
FX This research was funded by the University of Pavia under the Blue Sky
   Research Program (grant No. 1744747), University of Pavia, Dept. of Drug
   Sciences' Research Funding FRG 2021 [M.A]; by the University of
   Bologna-public research funding [M.R.]; the European Union's Horizon
   2020 research and innovation program under the Marie Sklodowska-Curie
   grant agreement No. 722717; the Academy of Finland (296840, 333302); the
   Kuopio University Hospital VTR grant (5503770); the Sigrid Juselius
   Foundation; the Paivikki and Sakari Sohlberg Foundation; the University
   of Eastern Finland strategical support and the Finnish Eye Foundation
   [K.K.].
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NR 53
TC 1
Z9 1
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD JUL
PY 2022
VL 11
IS 7
AR 1385
DI 10.3390/antiox11071385
PG 17
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 3G8OM
UT WOS:000831607200001
PM 35883876
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Chung, SH
   Sin, TN
   Dang, B
   Ngo, T
   Lo, T
   Lent-Schochet, D
   Meleppat, RK
   Zawadzki, RJ
   Yiu, G
AF Chung, Sook Hyun
   Sin, Tzu-Ni
   Dang, Brian
   Ngo, Taylor
   Lo, Therlinder
   Lent-Schochet, Daniella
   Meleppat, Ratheesh K.
   Zawadzki, Robert J.
   Yiu, Glenn
TI CRISPR-based VEGF suppression using paired guide RNAs for treatment of
   choroidal neovascularization
SO MOLECULAR THERAPY-NUCLEIC ACIDS
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; DOUBLE-STRANDED
   BREAKS; GEOGRAPHIC ATROPHY; GENE; CELLS; EXPRESSION; THERAPY; RISK
AB Clustered regularly interspaced short palindromic repeats (CRISPR)-based genomic disruption of vascular endothelial growth factor A (Vegfa) with a single gRNA suppresses choroidal neovascularization (CNV) in preclinical studies, offering the prospect of long-term anti-angiogenesis therapy for neovascular age-related macular degeneration (AMD). Genome editing using CRISPR-CRISPR-associated endonucleases (Cas9) with multiple guide RNAs (gRNAs) can enhance geneablation efficacy by augmenting insertion-deletion (indel) mutations with gene truncations but may also increase the risk of off-target effects. In this study, we compare the effectiveness of adeno-associated virus (AAV)-mediated CRISPR-Cas9 systems using single versus paired gRNAs to target two different loci in the Vegfa gene that are conserved in human, rhesus macaque, and mouse. Paired gRNAs increased Vegfa gene-ablation rates in human cells in vitro but did not enhance VEGF suppression in mouse eyes in vivo. Genome editing using paired gRNAs also showed a similar degree of CNV suppression compared with single-gRNA systems. Unbiased genome-wide analysis using genome-wide unbiased identification of double-stranded weak off-target activity arising from the second gRNA. These findings suggest that in vivo CRISPR-Cas9 genome editing using two gRNAs may increase gene ablation but also the potential risk of off-target mutations, while the functional benefit of targeting an additional locus in the Vegfa gene as treatment for neovascular retinal conditions is unclear.
C1 [Chung, Sook Hyun; Sin, Tzu-Ni; Dang, Brian; Ngo, Taylor; Lo, Therlinder; Lent-Schochet, Daniella; Meleppat, Ratheesh K.; Zawadzki, Robert J.; Yiu, Glenn] Univ Calif Davis, UC Davis Eye Ctr, Dept Ophthalmol & Vision Sci, UC Davis Hlth, Davis, CA 95616 USA.
C3 University of California System; University of California Davis
RP Yiu, G (通讯作者)，Univ Calif Davis, Dept Ophthalmol Vision Sci, 4860 St,Suite 2400, Davis, CA 95817 USA.
EM gyiu@ucdavis.edu
RI Meleppat, Ratheesh Kumar/AAG-4806-2020
OI Meleppat, Ratheesh Kumar/0000-0003-0240-9419
FU UC Davis Comprehensive Support Grant - NCI [P30CA093373]; NIH [P30
   EY012576]; BrightFocus Foundation; Macula Society
FX The authors thank John Douglas McPherson at UC Davis Health Integrated
   Genetics and Genomics core facility and The Genomics Shared Resource,
   supported by the UC Davis Comprehensive Support Grant (CCSG) funded by
   NCI P30CA093373, for GUIDE-seq analyses and advice. G.Y. is supported by
   NIH R01 EY032238 and R21 EY031108, the BrightFocus Foundation, and the
   Macula Society. R.Z. is supported by NIH R01 EY026556 and R01 EY031098.
   Histological studies were conducted at the UC Davis Center for Vision
   Sciences Structure-Function core facility, AAV production was conducted
   at the Molecular Packaging and Construct core facility, and in vivo
   mouse imaging was conducted at the Small Animal Ocular Imaging core
   facility, all of which are supported by NIH P30 EY012576. The funding
   organizations did not play any role in the design or conduct of this
   retrospective study; the collection, management, analysis, or
   interpretation of data; or the preparation, review, approval, or
   submission decision of the manuscript. The content is solely the
   responsibility of the authors and does not necessarily represent the
   official views of the funding agencies.
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NR 54
TC 0
Z9 0
U1 8
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 2162-2531
J9 MOL THER-NUCL ACIDS
JI Mol. Ther.-Nucl. Acids
PD JUN 14
PY 2022
VL 28
BP 613
EP 622
DI 10.1016/j.omtn.2022.04.015
PG 10
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA 1W1CH
UT WOS:000806517200032
PM 35614998
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Bu, Y
   Chan, YK
   Wong, HL
   Poon, SHL
   Lo, ACY
   Shih, KC
   Tong, L
AF Bu, Yashan
   Chan, Yau-Kei
   Wong, Ho-Lam
   Poon, Stephanie Hiu-Ling
   Lo, Amy Cheuk-Yin
   Shih, Kendrick Co
   Tong, Louis
TI A Review of the Impact of Alterations in Gut Microbiome on the
   Immunopathogenesis of Ocular Diseases
SO JOURNAL OF CLINICAL MEDICINE
LA English
DT Review
DE ocular disease; intestinal microbiota; autoimmune diseases; immune
   homeostasis
ID INTESTINAL MICROBIOTA; AUTOIMMUNITY; RESPONSES; BACTERIAL; TH17
AB Recent studies have highlighted the association between ocular diseases and microbiota profiles of the host intestinal tract and oral cavity. There is mounting evidence supporting the existence of a 'gut-eye axis', whereby changes in gut microbiome alter host immunity, with consequential implications for ocular health and disease. In this review, we examined recent published findings on the association between gut microbiome and ocular morbidity, based on 25 original articles published between 2011 to 2020. The review included both clinical and in vivo animal studies, with particular focus on the influence of the microbiome on host immunity and metabolism. Significant associations between altered intestinal microbiome and specific ocular diseases and pathological processes, including Behcet's syndrome, autoimmune uveitis, age-related macular degeneration, choroidal neovascularization, bacterial keratitis, and Sjogren-like lacrimal keratoconjunctivitis have been demonstrated. Furthermore, alterations in the gut microbiome resulted in quantifiable changes in the host immune response, suggesting immunopathogenesis as the basis for the link between intestinal dysbiosis and ocular disease. We also examined and compared different techniques used in the identification and quantification of gut microorganisms. With our enhanced understanding of the potential role of gut commensals in ophthalmic disease, the stage is set for further studies on the underlying mechanisms linking the gut microbiome, the host immune response, and the pathogenesis of ophthalmic disease.</p>
C1 [Bu, Yashan; Chan, Yau-Kei; Wong, Ho-Lam; Poon, Stephanie Hiu-Ling; Lo, Amy Cheuk-Yin; Shih, Kendrick Co] Univ Hong Kong, Li Ka Shing Fac Med, Dept Ophthalmol, Hong Kong, Peoples R China.
   [Tong, Louis] Singapore Natl Eye Ctr, Cornea & External Eye Dis Serv, Singapore 168751, Singapore.
   [Tong, Louis] Singapore Eye Res Inst, Ocular Surface Res Grp, Singapore 169856, Singapore.
C3 University of Hong Kong; Singapore National Eye Center; National
   University of Singapore; Singapore National Eye Center
RP Shih, KC (通讯作者)，Univ Hong Kong, Li Ka Shing Fac Med, Dept Ophthalmol, Hong Kong, Peoples R China.
EM u3005204@connect.hku.hk; josephyk@connect.hku.hk; whlww@connect.hku.hk;
   stephaniehlpoon@gmail.com; amylo@hku.hk; kcshih@hku.hk;
   louis.tong.h.t@singhealth.com.sg
RI Shih, Kendrick Co/E-9883-2010; Lo, Amy C. Y./C-1195-2009
OI Shih, Kendrick Co/0000-0001-6255-2941; Lo, Amy C.
   Y./0000-0003-4239-6851; Poon, Stephanie/0000-0003-4631-3902; Bu, Ophelia
   Yashan/0000-0003-1637-8182; Wong, William Ho Lam/0000-0003-1708-2084;
   Tong, Louis/0000-0002-3986-6552
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NR 61
TC 4
Z9 4
U1 2
U2 5
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2077-0383
J9 J CLIN MED
JI J. Clin. Med.
PD OCT
PY 2021
VL 10
IS 20
AR 4694
DI 10.3390/jcm10204694
PG 12
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA WS9RG
UT WOS:000715512400001
PM 34682816
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hsu, MY
   Hsiao, YP
   Lin, YT
   Chen, C
   Lee, CM
   Liao, WC
   Tsou, SC
   Lin, HW
   Chang, YY
AF Hsu, Min-Yen
   Hsiao, Yai-Ping
   Lin, Yu-Ta
   Chen, Connie
   Lee, Chee-Ming
   Liao, Wen-Chieh
   Tsou, Shang-Chun
   Lin, Hui-Wen
   Chang, Yuan-Yen
TI Quercetin Alleviates the Accumulation of Superoxide in Sodium
   Iodate-Induced Retinal Autophagy by Regulating Mitochondrial Reactive
   Oxygen Species Homeostasis through Enhanced Deacetyl-SOD2 via the
   Nrf2-PGC-1 alpha-Sirt1 Pathway
SO ANTIOXIDANTS
LA English
DT Article
DE age-related macular degeneration; sodium iodate; retinal pigment
   epithelium; quercetin; oxidative stress; autophagy; mitochondrial
   biogenesis
ID OXIDATIVE STRESS; MACULAR DEGENERATION; RPE; INFLAMMATION; MECHANISM;
   SIRT1
AB Oxidative damage of retinal pigment epithelium (RPE) cells plays an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Quercetin, a bioactive flavonoid compound, has been shown to have a protective effect against oxidative stress-induced cell apoptosis and inflammation in RPE cells; however, the detailed mechanism underlying this protective effect is unclear. Therefore, the aim of this study was to investigate the regulatory mechanism of quercetin in a sodium iodate (NaIO3)-induced retinal damage. The clinical features of the mice, the production of oxidative stress, and the activity of autophagy and mitochondrial biogenesis were examined. In the mouse model, NaIO3 treatment caused changes in the retinal structure and reduced pupil constriction, and quercetin treatment reversed the oxidative stress-related pathology by decreasing the level of superoxide dismutase 2 (SOD2) while enhancing the serum levels of catalase and glutathione. The increased level of reactive oxygen species in the NaIO3-treated ARPE19 cells was improved by treatment with quercetin, accompanied by a reduction in autophagy and mitochondrial biogenesis. Our findings indicated that the effects of quercetin on regulating the generation of mtROS were dependent on increased levels of deacetyl-SOD2 through the Nrf2-PGC-1 alpha-Sirt1 signaling pathway. These results demonstrated that quercetin may have potential therapeutic efficacy for the treatment of AMD through the regulation of mtROS homeostasis.
C1 [Hsu, Min-Yen; Hsiao, Yai-Ping; Lin, Yu-Ta; Lee, Chee-Ming; Chang, Yuan-Yen] Chung Shan Med Univ, Sch Med, Taichung 40201, Taiwan.
   [Hsu, Min-Yen; Hsiao, Yai-Ping; Lin, Yu-Ta; Lee, Chee-Ming] Chung Shan Med Univ Hosp, Dept Ophthalmol, Taichung 40201, Taiwan.
   [Hsu, Min-Yen] Natl Chung Hsing Univ, Biotechnol Ctr, Taichung 40227, Taiwan.
   [Chen, Connie; Liao, Wen-Chieh] Chung Shan Med Univ, Dept Optometry, Taichung 40201, Taiwan.
   [Chen, Connie] Chung Shan Med Univ, Inst Optometry, Taichung 40201, Taiwan.
   [Liao, Wen-Chieh] Chung Shan Med Univ, Fac Med, Dept Anat, Taichung 40201, Taiwan.
   [Tsou, Shang-Chun] Chung Shan Med Univ, Dept Nutr, Taichung 40201, Taiwan.
   [Lin, Hui-Wen] Asia Univ, Dept Optometry, Taichung 41354, Taiwan.
   [Lin, Hui-Wen] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40447, Taiwan.
   [Chang, Yuan-Yen] Chung Shan Med Univ Hosp, Dept Med Educ, Taichung 40201, Taiwan.
C3 Chung Shan Medical University; Chung Shan Medical University; Chung Shan
   Medical University Hospital; National Chung Hsing University; Chung Shan
   Medical University; Chung Shan Medical University; Chung Shan Medical
   University; Chung Shan Medical University; Asia University Taiwan; China
   Medical University Taiwan; China Medical University Hospital - Taiwan;
   Chung Shan Medical University; Chung Shan Medical University Hospital
RP Chang, YY (通讯作者)，Chung Shan Med Univ, Sch Med, Taichung 40201, Taiwan.; Lin, HW (通讯作者)，Asia Univ, Dept Optometry, Taichung 41354, Taiwan.; Lin, HW (通讯作者)，China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40447, Taiwan.; Chang, YY (通讯作者)，Chung Shan Med Univ Hosp, Dept Med Educ, Taichung 40201, Taiwan.
EM my.scott.hsu@gmail.com; amy1234575@gmail.com; yuta0301156@gmail.com;
   cconnie7@gmail.com; jimboy85@gmail.com; khrnange@csmu.edu.tw;
   eq7bie5d@gmail.com; d9138001@asia.edu.tw; cyy0709@csmu.edu.tw
OI Hsu, Min-Yen/0000-0002-5488-4257; Chang, Yuan-Yen/0000-0001-6395-4280;
   Liao, Wen Chieh/0000-0001-7848-2124
FU Chung Shan Medical University [NCHU-CSMU-10708, NCHU-CSMU-10910,
   CSH-2020-C-027]; Ministry of Science and Technology,Taiwan
   [MOST-107-2311-B-468-001, MOST-108-2320-B-468-002,
   MOST-109-2320-B-468-004-MY3, MOST-110-2636-E-040-001]
FX The authors would like to thank the Chung Shan Medical University
   (project numbers: NCHU-CSMU-10708, NCHU-CSMU-10910, and CSH-2020-C-027)
   and the Ministry of Science and Technology,Taiwan (project numbers:
   MOST-107-2311-B-468-001, MOST-108-2320-B-468-002,
   MOST-109-2320-B-468-004-MY3, and MOST-110-2636-E-040-001, Columbus
   program of MOST Young Scholar) for financially supporting this research.
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NR 60
TC 9
Z9 9
U1 3
U2 12
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD JUL
PY 2021
VL 10
IS 7
AR 1125
DI 10.3390/antiox10071125
PG 16
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 TN0NT
UT WOS:000675942100001
PM 34356358
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Arjunan, P
   Swaminathan, R
   Yuan, JS
   Elashiry, M
   Tawfik, A
   Al-Shabrawey, M
   Martin, PM
   Muthusamy, T
   Cutler, CW
AF Arjunan, Pachiappan
   Swaminathan, Radhika
   Yuan, Jessie
   Elashiry, Mohamed
   Tawfik, Amany
   Al-Shabrawey, Mohamed
   Martin, Pamela M.
   Muthusamy, Thangaraju
   Cutler, Christopher W.
TI Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic
   Oral Pathogens
SO ANTIOXIDANTS
LA English
DT Article
DE age-related macular degeneration; retinal inflammation; oxidative
   stress; antioxidants; retinal degeneration; periodontal disease;
   therapeutic targets
AB Emerging evidence underscores an association between age-related macular degeneration (AMD) and periodontal disease (PD), yet the biological basis of this linkage and the specific role of oral dysbiosis caused by PD in AMD pathophysiology remains unclear. Furthermore, a simple reproducible model that emulates characteristics of both AMD and PD has been lacking. Hence, we established a novel AMD+PD murine model to decipher the potential role of oral infection (ligature-enhanced) with the keystone periodontal pathogen Porphyromonas gingivalis, in the progression of neovasculogenesis in a laser-induced choroidal-neovascularization (Li-CNV) mouse retina. By a combination of fundus photography, optical coherence tomography, and fluorescein angiography, we documented inflammatory drusen-like lesions, reduced retinal thickness, and increased vascular leakage in AMD+PD mice retinae. H&E further confirmed a significant reduction of retinal thickness and subretinal drusen-like deposits. Immunofluorescence microscopy revealed significant induction of choroidal/retinal vasculogenesis in AMD+PD mice. qPCR identified increased expression of oxidative-stress, angiogenesis, pro-inflammatory mediators, whereas antioxidants and anti-inflammatory genes in AMD+PD mice retinae were notably decreased. Through qPCR, we detected Pg and its fimbrial 16s-RrNA gene expression in the AMD+PD mice retinae. To sum-up, this is the first in vivo study signifying a role of periodontal infection in augmentation of AMD phenotype, with the aid of a pioneering AMD+PD murine model established in our laboratory.
C1 [Arjunan, Pachiappan; Swaminathan, Radhika; Yuan, Jessie; Elashiry, Mohamed; Cutler, Christopher W.] Dent Coll Georgia, Dept Periodont, Augusta, GA 30912 USA.
   [Arjunan, Pachiappan; Tawfik, Amany; Al-Shabrawey, Mohamed; Martin, Pamela M.] Augusta Univ, Vis Discovery Inst, Augusta, GA 30912 USA.
   [Tawfik, Amany; Al-Shabrawey, Mohamed] Augusta Univ, Dept Oral Biol & Diagnost Sci, Augusta, GA 30912 USA.
   [Martin, Pamela M.; Muthusamy, Thangaraju] Augusta Univ, Dept Biochem & Mol Biol, Augusta, GA 30912 USA.
C3 University System of Georgia; Augusta University; University System of
   Georgia; Augusta University; University System of Georgia; Augusta
   University
RP Arjunan, P (通讯作者)，Dent Coll Georgia, Dept Periodont, Augusta, GA 30912 USA.; Arjunan, P (通讯作者)，Augusta Univ, Vis Discovery Inst, Augusta, GA 30912 USA.
EM parjunan@augusta.edu; rswaminathan@augusta.edu; jeyuan@augusta.edu;
   moelashiry@augusta.edu; amtawfik@augusta.edu; malshabrawey@augusta.edu;
   pmmartin@augusta.edu; mthangaraju@augusta.edu; chcutler@augusta.edu
RI Elashiry, Mohamed Mohamed/AAI-5290-2020
OI Elashiry, Mohamed Mohamed/0000-0003-0880-4882; Tawfik,
   Amany/0000-0002-0245-8256
FU DCG Startup Fund; AU Intra-Mural Grant; Mason Trust Foundation
   [20000-02122000-12100-64050-MASON00002]
FX Supported by the DCG Startup Fund and AU Intra-Mural Grant (to P.A.),
   Mason Trust Foundation-20000-02122000-12100-64050-MASON00002 (to
   C.W.C.).
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NR 136
TC 4
Z9 4
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD FEB
PY 2021
VL 10
IS 2
AR 309
DI 10.3390/antiox10020309
PG 22
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 QM9CT
UT WOS:000622072100001
PM 33670526
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Lores-Padin, A
   Fernandez, B
   Alvarez, L
   Gonzalez-Iglesias, H
   Lengyel, I
   Pereiro, R
AF Lores-Padin, Ana
   Fernandez, Beatriz
   Alvarez, Lydia
   Gonzalez-Iglesias, Hector
   Lengyel, Imre
   Pereiro, Rosario
TI Multiplex bioimaging of proteins-related to neurodegenerative diseases
   in eye sections by laser ablation - Inductively coupled plasma - Mass
   spectrometry using metal nanoclusters as labels
SO TALANTA
LA English
DT Article
DE Metal nanoclusters; Bioimaging; Immunohistochemistry; Multiplex analysis
   of proteins; Age-related macular degeneration; Laser ablation ICP-MS
ID LA-ICP-MS; THIN-SECTIONS; COPPER; ZINC; DEPOSITS; TISSUES; DRUSEN; IRON;
   CELL
AB Simultaneous determination of proteins with micrometric resolution is a significant challenge. In this study, laser ablation (LA) inductively coupled plasma - mass spectrometry (ICP-MS) was employed to quantify the distribution of proteins associated to the eye disease age-related macular degeneration (AMD) using antibodies labelled with three different metal nanoclusters (MNCs). PtNCs, AuNCs and AgNCs contain hundreds of metal atoms and were used to detect metallothionein 1/2 (MT1/2), complement factor H (CFH) and amyloid precursor protein (APP) in retina, ciliary body, retinal pigment epithelium (RPE), choroid and sclera from human cadaveric eye sections. First, the labelling of MNCs bioconjugated primary antibodies (Ab) was optimised following an immunolabelling protocol to avoid the non-specific interaction of MNCs with the tissue. Then, the LA and ICP-MS conditions were studied to obtain high-resolution images for the simultaneous detection of the three labels at the same tissue section. A significant signal amplification was found when using AuNCs, AgNCs and PtNCs labelled Ab of 310, 723 and 1194 respectively. After the characterisation of MNCs labelled immunoprobes, the Ab labelling was used for determination of MT1/2, CFH and APP in the RPE-choroid-sclera, where accumulation of extracellular deposits related to AMD was observed. Experimental results suggest that this method is fully suitable for the simultaneous detection of at least three different proteins.
C1 [Lores-Padin, Ana; Fernandez, Beatriz; Pereiro, Rosario] Univ Oviedo, Dept Phys & Analyt Chem, Julian Claveria 8, Oviedo 33006, Spain.
   [Fernandez, Beatriz; Alvarez, Lydia; Gonzalez-Iglesias, Hector; Pereiro, Rosario] Univ Oviedo, Inst Univ Fernandez Vega, Fdn Invest Oftalmol, Oviedo, Spain.
   [Alvarez, Lydia; Gonzalez-Iglesias, Hector] Inst Oftalmol Fernandez Vega, Avda Dres Fernandez Vega 34, Oviedo 33012, Spain.
   [Lengyel, Imre] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Wellcome Wolfson Inst Expt Med, Belfast, Antrim, North Ireland.
C3 University of Oviedo; University of Oviedo; Queens University Belfast
RP Fernandez, B (通讯作者)，Univ Oviedo, Dept Phys & Analyt Chem, Julian Claveria 8, Oviedo 33006, Spain.; Gonzalez-Iglesias, H (通讯作者)，Univ Oviedo, Inst Univ Fernandez Vega, Fdn Invest Oftalmol, Oviedo, Spain.
EM fernandezbeatriz@uniovi.es; h.gonzalez@fio.as
RI Lengyel, Imre/B-5217-2009; Gonzalez-Iglesias, Hector/K-2447-2014;
   Fernandez, Beatriz/D-1685-2014; Alvarez, Lydia/AAA-7736-2019;
   Gonzalez-Iglesias, Hector/AAB-5993-2019
OI Lengyel, Imre/0000-0001-7467-2174; Gonzalez-Iglesias,
   Hector/0000-0001-5251-0967; Fernandez, Beatriz/0000-0002-2592-1442;
   Lores Padin, Ana/0000-0002-5564-591X; Alvarez Fernandez,
   Lydia/0000-0002-0604-7411
FU Agencia Estatal de Investigacion (Spain) [CTQ201679015-R]; FEDER; FPU
   Grant (Ministry of Education) [MECD-17-FPU16/01363]; "Ramon y Cajal
   Program" (Ministry of Economy and Competitiveness) [RYC-2014-14985];
   Belfast Association for the Blind; "Eye-Risk" European Union's Horizon
   2020 research and innovation program [634479]; National Institute for
   Health Research
FX This work was financially supported through project CTQ201679015-R by
   Agencia Estatal de Investigacion (Spain) and FEDER. A. Lores-Padin and
   B. Fernandez respectively acknowledge the FPU Grant (Ref.
   MECD-17-FPU16/01363; Ministry of Education) and the contract
   RYC-2014-14985 through the "Ramon y Cajal Program" (Ministry of Economy
   and Competitiveness). This research was also supported by a grant from
   the Belfast Association for the Blind and the "Eye-Risk" European
   Union's Horizon 2020 research and innovation program (grant ref.:
   634479) (I.L). Tissue for this project was provided by the University
   College London Institute of Ophthalmology and Moorfields Eye Hospital
   Eye Tissue Repository supported by National Institute for Health
   Research funding.
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NR 37
TC 12
Z9 12
U1 5
U2 56
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0039-9140
EI 1873-3573
J9 TALANTA
JI Talanta
PD JAN 1
PY 2021
VL 221
AR 121489
DI 10.1016/j.talanta.2020.121489
PG 10
WC Chemistry, Analytical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry
GA OD5RI
UT WOS:000579910600053
PM 33076097
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Karniel, U
   Koch, A
   Zamir, D
   Hirschberg, J
AF Karniel, Uri
   Koch, Amit
   Zamir, Dani
   Hirschberg, Joseph
TI Development of zeaxanthin-rich tomato fruit through genetic
   manipulations of carotenoid biosynthesis
SO PLANT BIOTECHNOLOGY JOURNAL
LA English
DT Article
DE zeaxanthin; carotenoid biosynthesis; metabolic engineering;
   antioxidants; AMD
ID LYCOPENE BETA-CYCLASE; MACULAR DEGENERATION; PROTECTIVE ROLE; EYE
   DISEASE; PATHWAY; LUTEIN; CHROMOPLASTS; EXPRESSION; PIGMENT; MUTANT
AB The oxygenated carotenoid zeaxanthin provides numerous benefits to human health due to its antioxidant properties. Especially it is linked to protecting, together with the xanthophyll lutein, the retina in the human eye by filtering harmful blue light thus delaying the progression of age-related macular degeneration (AMD), the most prevalent cause of blindness in developed countries. Despite its high nutritional value, zeaxanthin is less available than other substantial carotenoids in our diet. To solve this shortage, we chose to develop a new food source that would contain a high concentration of natural zeaxanthin. Tomato (Solanum lycopersicum L.) was selected as the target plant since it is the second largest vegetable crop grown worldwide and its fruit characteristically synthesizes and accumulates a high concentration of carotenoids. We employed two genetic approaches in order to enhance zeaxanthin biosynthesis in tomato fruit: a transgenic metabolic engineering and classical genetic breeding. A nontransgenic tomato line, named 'Xantomato', was generated whose fruit accumulated zeaxanthin at a concentration of 39 mu g/g fresh weight (or 577 mu g/g dry weight), which comprised ca. 50% of total fruit carotenoids compared to zero in the wild type. This is the highest concentration of zeaxanthin reached in a primary crop. Xantomato can potentially increase zeaxanthin availability in the human diet and serve as raw material for industrial applications.
C1 [Karniel, Uri; Hirschberg, Joseph] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Genet, Jerusalem, Israel.
   [Koch, Amit; Zamir, Dani] Hebrew Univ Jerusalem, Robert H Smith Inst Plant Sci & Genet, Rehovot, Israel.
C3 Hebrew University of Jerusalem; Hebrew University of Jerusalem
RP Hirschberg, J (通讯作者)，Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Genet, Jerusalem, Israel.
EM hirschu@mail.huji.ac.il
FU Israel Science Foundation [850/13]; EC FP7 KBBE programme DISCO [613513]
FX We thank Dr. Yael Friedmann for her proficient assistance with the
   transmission electron microscopy and Marc Simanowitz and Nurit Bar-Nun
   for the valuable comments on the manuscript. This research was supported
   by the Israel Science Foundation grant 850/13, and by EC FP7 KBBE
   programme DISCO, project 613513.
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NR 100
TC 21
Z9 21
U1 4
U2 37
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1467-7644
EI 1467-7652
J9 PLANT BIOTECHNOL J
JI Plant Biotechnol. J.
PD NOV
PY 2020
VL 18
IS 11
BP 2292
EP 2303
DI 10.1111/pbi.13387
EA MAY 2020
PG 12
WC Biotechnology & Applied Microbiology; Plant Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Plant Sciences
GA OH4FP
UT WOS:000531382200001
PM 32320515
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ozkan, J
   Willcox, MD
AF Ozkan, Jerome
   Willcox, Mark D.
TI The Ocular Microbiome: Molecular Characterisation of a Unique and Low
   Microbial Environment
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Microbiome; 16S rRNA gene; microbiology; conjunctiva; human; health;
   disease
ID CONJUNCTIVAL MICROBIOME; BACTERIAL-FLORA; CONTACT-LENS; 16S RDNA;
   IDENTIFICATION; SURFACE; DNA; DIVERSITY; PCR; CONTAMINATION
AB Aim: The ocular surface is continually exposed to bacteria from the environment and traditional culture-based microbiological studies have isolated a low diversity of microorganisms from this region. The use of culture-independent methods to define the ocular microbiome, primarily involving 16S ribosomal RNA gene sequencing studies, have shown that the microbial communities present on the ocular surface have a greater diversity than previously reported. Method: A review of the literature on ocular microbiome research in health and disease. Results: Molecular techniques have been used to investigate the effect of contact lens wear and disease on the microbiota of the ocular surface and eyelids and the immunoregulatory role of the ocular surface microbiota. Studies have shown that compositional changes in the microbiota occur in ocular surface disorders such as blepharitis, trachoma and dry eye and also suggest a role of the ocular and non-ocular microbiome in retinal disease including age-related macular degeneration, glaucoma, uveitis and diabetic retinopathy. However, ocular microbiome studies need to recognise the potential for contamination to impact findings and carefully control each stage of the experimental procedure and to utilise statistical methods to identify contamination signals. Conclusion: The healthy ocular surface is characterised by a relatively stable, comparatively low diversity microbiome with recent findings that the bacteria of the ocular surface appear to have a role in maintaining homeostasis by modulating immune function.
C1 [Ozkan, Jerome; Willcox, Mark D.] Univ New South Wales, Sch Optometry & Vis Sci, Sydney, NSW 2052, Australia.
   [Ozkan, Jerome] Univ New South Wales, Sch Biol Earth & Environm Sci, Sydney, NSW, Australia.
C3 University of New South Wales Sydney; University of New South Wales
   Sydney
RP Ozkan, J (通讯作者)，Univ New South Wales, Sch Optometry & Vis Sci, Sydney, NSW 2052, Australia.
EM j.ozkan@unsw.edu.au
RI Ozkan, Jerome/S-8545-2019
OI Ozkan, Jerome/0000-0001-6194-1128
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NR 76
TC 49
Z9 51
U1 0
U2 9
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 JUL 3
PY 2019
VL 44
IS 7
BP 685
EP 694
DI 10.1080/02713683.2019.1570526
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OP0ID
UT WOS:000587758200001
PM 30640553
DA 2022-11-30
ER

PT J
AU Polesskaya, O
   Kananykhina, E
   Roy-Engel, AM
   Nazarenko, O
   Kulemzina, I
   Baranova, A
   Vassetsky, Y
   Myakishev-Rempel, M
AF Polesskaya, Oksana
   Kananykhina, Evgeniya
   Roy-Engel, Astrid M.
   Nazarenko, Olga
   Kulemzina, Irina
   Baranova, Ancha
   Vassetsky, Yegor
   Myakishev-Rempel, Max
TI The role of Alu-derived RNAs in Alzheimer's and other neurodegenerative
   conditions
SO MEDICAL HYPOTHESES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; LONG NONCODING RNAS; STRESS GRANULES;
   IDENTIFIES VARIANTS; COMMON VARIANTS; BINDING-SITES; DISEASE;
   RECOGNITION; TRANSCRIPTION; EXPRESSION
AB Non-coding RNAs have emerged as essential contributors to neuroinflammation. The Alu element is the most abundant potential source of non-coding RNA in the human genome represented by over 1.1 million copies totaling similar to 10% of the genome's mass. Accumulation of "Alu RNA" was observed in the brains of individuals with dementia and Creutzfeldt-Jakob disease - a degenerative brain disorder. "Alu RNAs" activate inflammatory pathways and apoptosis in the non-neural cells. In particular, the "Alu RNA" cytotoxicity is suggested as a mechanism in retinal pigment epithelium (RPE), a compartment damaged in the process of age-related macular degeneration. In RPE cells, the deficiency of Dicer is reported to lead to an accumulation of P3Alu transcripts, subsequent activation of the ERK1/2 signaling pathway, and the formation of NLRP3 inflammasome. In turn, these events result in RPE cell death by apoptosis. Importantly, RPE cells are of neuroectodermal origin, these cells display more similarity to neurons than to other epithelial cells. Thus, it is plausible that the mechanisms of "Alu RNA" cytotoxicity in brain neurons are similar to that in RPE. We hypothesize that accumulation of polymerase III-transcribed noncoding RNA of Alu (P3Alu) may contribute to both neuroinflammation and neurodegeneration associated with Alzheimer's disease (AD) and other degenerative brain disorders. This hypothesis points toward a novel molecular pathway not previously considered for the treatment of AD.
C1 [Polesskaya, Oksana] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
   [Kananykhina, Evgeniya] Kulakov Natl Med Res Ctr Obstet Gynecol & Perinat, Moscow, Russia.
   [Roy-Engel, Astrid M.] Tulane Univ, New Orleans, LA 70118 USA.
   [Nazarenko, Olga; Kulemzina, Irina; Myakishev-Rempel, Max] Biophys Res Inst, San Diego, CA USA.
   [Baranova, Ancha] George Mason Univ, Sch Syst Biol, Fairfax, VA 22030 USA.
   [Baranova, Ancha] Res Ctr Med Genet, Moscow, Russia.
   [Vassetsky, Yegor] Univ Paris Sud, CNRS, Inst Gustave Roussy, UMR8126, Villejuif, France.
   [Vassetsky, Yegor] RAS, Koltzov Inst Dev Biol, Moscow, Russia.
   [Myakishev-Rempel, Max] Vaccine Res Inst San Diego, San Diego, CA USA.
   [Myakishev-Rempel, Max] Localized Therapeut LLC, San Diego, CA USA.
C3 University of California System; University of California San Diego;
   Tulane University; George Mason University; Research Centre for Medical
   Genetics; Centre National de la Recherche Scientifique (CNRS); CNRS -
   National Institute for Biology (INSB); UDICE-French Research
   Universities; Universite Paris Saclay; UNICANCER; Gustave Roussy;
   Russian Academy of Sciences; Koltzov Institute of Developmental Biology
   of the Russian Academy of Sciences
RP Myakishev-Rempel, M (通讯作者)，8020 Ave Navidad,Suite 43, San Diego, CA 92122 USA.
EM mrempel@vrisd.org
RI Vassetzky, Yegor S/C-6447-2008; , Ancha/B-4608-2012; Kananykhina,
   Evgeniya Y/A-8228-2014; Polesskaya, Oksana/AAX-9283-2021
OI Vassetzky, Yegor S/0000-0003-3101-7043; , Ancha/0000-0001-6810-5982;
   Kananykhina, Evgeniya Y/0000-0002-9779-2918; Engel,
   Astrid/0000-0002-8884-4544
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NR 106
TC 8
Z9 8
U1 0
U2 10
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 JUN
PY 2018
VL 115
BP 29
EP 34
DI 10.1016/j.mehy.2018.03.008
PG 6
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA GG5UZ
UT WOS:000432762500008
PM 29685192
DA 2022-11-30
ER

PT J
AU Girish, GN
   Anima, VA
   Kothari, AR
   Sudeep, PV
   Roychowdhury, S
   Rajan, J
AF Girish, G. N.
   Anima, V. A.
   Kothari, Abhishek R.
   Sudeep, P. V.
   Roychowdhury, Sohini
   Rajan, Jeny
TI A benchmark study of automated intra-retinal cyst segmentation
   algorithms using optical coherence tomography B-scans
SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
LA English
DT Article
DE Computer-aided diagnostics; Cyst; Macular edema; Optical coherence
   tomography; Retinal image; Segmentation
ID IMAGES
AB (Background and objectives): Retinal cysts are formed by accumulation of fluid in the retina caused by leakages from inflammation or vitreous fractures. Analysis of the retinal cystic spaces holds significance in detection and treatment of several ocular diseases like age-related macular degeneration, diabetic macular edema etc. Thus, segmentation of intra-retinal cysts and quantification of cystic spaces are vital for retinal pathology and severity detection. In the recent years, automated segmentation of intra-retinal cysts using optical coherence tomography B-scans has gained significant importance in the field of retinal image analysis. The objective of this paper is to compare different intra-retinal cyst segmentation algorithms for comparative analysis and benchmarking purposes.
   (Methods): In this work, we employ a modular approach for standardizing the different segmentation algorithms. Further, we analyze the variations in automated cyst segmentation performances and method scalability across image acquisition systems by using the publicly available cyst segmentation challenge dataset (OPTIMA cyst segmentation challenge).
   (Results): Several key automated methods are comparatively analyzed using quantitative and qualitative experiments. Our analysis demonstrates the significance of variations in signal-to-noise ratio (SNR), retinal layer morphology and post-processing steps on the automated cyst segmentation processes.
   (Conclusion): This benchmarking study provides insights towards the scalability of automated processes across vendor-specific imaging modalities to provide guidance for retinal pathology diagnostics and treatment processes. (C) 2017 Elsevier B.V. Allrights reserved.
C1 [Girish, G. N.; Anima, V. A.; Rajan, Jeny] Natl Inst Technol Karnataka, Dept Comp Sci & Engn, Surathkal, India.
   [Kothari, Abhishek R.] Pink City Eye & Retina Ctr, Jaipur, Rajasthan, India.
   [Sudeep, P. V.] Natl Inst Technol Karnataka, Dept Elect & Commun Engn, Surathkal, India.
   [Sudeep, P. V.] Manipal Inst Technol, Dept Elect & Commun Engn, Manipal, Karnataka, India.
   [Roychowdhury, Sohini] Univ Washington, Dept Elect & Comp Engn, Bothell, WA USA.
C3 National Institute of Technology (NIT System); National Institute of
   Technology Karnataka; National Institute of Technology (NIT System);
   National Institute of Technology Karnataka; Manipal Academy of Higher
   Education (MAHE); University of Washington; University of Washington
   Bothell
RP Girish, GN (通讯作者)，Natl Inst Technol Karnataka, Dept Comp Sci & Engn, Surathkal, India.
EM girishanit@gmail.com
RI N, Girish G/AAL-7597-2020; Rajan, Jeny/G-9484-2011
OI N, Girish G/0000-0003-2101-2388; Rajan, Jeny/0000-0001-8045-6005; P.V.,
   Sudeep/0000-0002-6738-7786
FU Science and Engineering Research Board (Department of Science and
   Technology, India) [EMR/2016/002677]
FX This work was supported by the Science and Engineering Research Board
   (Department of Science and Technology, India) through project funding
   EMR/2016/002677.
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NR 29
TC 11
Z9 11
U1 1
U2 9
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 JAN
PY 2018
VL 153
BP 105
EP 114
DI 10.1016/j.cmpb.2017.10.010
PG 10
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 FO1HD
UT WOS:000416507300012
PM 29157443
DA 2022-11-30
ER

PT J
AU Busch, C
   Annamalai, B
   Abdusalamova, K
   Reichhart, N
   Huber, C
   Lin, YC
   Jo, EAH
   Zipfel, PF
   Skerka, C
   Wildner, G
   Diedrichs-Mohring, M
   Rohrer, B
   Strauss, O
AF Busch, Catharina
   Annamalai, Balasubramaniam
   Abdusalamova, Khava
   Reichhart, Nadine
   Huber, Christian
   Lin, Yuchen
   Jo, Emeraldo A. H.
   Zipfel, Peter F.
   Skerka, Christine
   Wildner, Gerhild
   Diedrichs-Moehring, Maria
   Rohrer, Barbel
   Strauss, Olaf
TI Anaphylatoxins Activate Ca2+, Akt/PI3-Kinase, and FOXO1/FoxP3 in the
   Retinal Pigment Epithelium
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE anaphylatoxins; calcium signaling; FOXO1; FoxP3; retinal pigment
   epithelium
ID COMPLEMENT FACTOR-H; T-CELL HOMEOSTASIS; MACULAR DEGENERATION; VEGF
   SECRETION; NUCLEAR CALCIUM; ANGIOTENSIN-II; EXPRESSION; C5A; C3A;
   RECEPTOR
AB Purpose: The retinal pigment epithelium (RPE) is a main target for complement activation in age-related macular degeneration (AMD). The anaphylatoxins C3a and C5a have been thought to mostly play a role as chemoattractants for macrophages and immune cells; here, we explore whether they trigger RPE alterations. Specifically, we investigated the RPE as a potential immunoregulatory gate, allowing for active changes in the RPE microenvironment in response to complement.
   Design: In vitro and in vivo analysis of signaling pathways.
   Methods: Individual activities of and interaction between the two anaphylatoxin receptors were tested in cultured RPE cells by fluorescence microscopy, western blot, and immunohistochemistry. Main outcome measures: Intracellular free calcium, protein phosphorylation, immunostaining of tissues/cells, and multiplex secretion assay.
   Results: Similar to immune cells, anaphylatoxin exposure resulted in increases in free cytosolic Ca2+, PI3-kinase/Akt activation, FoxP3 and FOXO1 phosphorylation, and cytokine/chemokine secretion. Differential responses were elicited depending on whether C3a and C5a were co-administered or applied consecutively, and response amplitudes in co-administration experiments ranged from additive to driven by C5a (C3a + C5a = C5a) or being smaller than those elicited by C3a alone (C3a + C5a < C3a).
   Conclusion: We suggest that this combination of integrative signaling between C3aR and C5aR helps the RPE to precisely adopt its immune regulatory function. These data further contribute to our understanding of AMD pathophysiology.
C1 [Busch, Catharina; Abdusalamova, Khava; Reichhart, Nadine; Huber, Christian; Strauss, Olaf] Charite Univ Med Berlin, Dept Ophthalmol, Berlin, Germany.
   [Busch, Catharina] Berlin Inst Hlth, Berlin, Germany.
   [Annamalai, Balasubramaniam; Rohrer, Barbel] Med Univ South Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Huber, Christian] Heidelberg Univ, Dept Ophthalmol, Heidelberg, Germany.
   [Lin, Yuchen; Jo, Emeraldo A. H.; Zipfel, Peter F.; Skerka, Christine] Leibniz Inst Nat Prod Res & Infect Biol, Dept Infect Biol, Jena, Germany.
   [Wildner, Gerhild; Diedrichs-Moehring, Maria] Clin LMU Munich, Sect Immunobiol, Dept Ophthalmol, Munich, Germany.
   [Rohrer, Barbel] Ralph H Johnson VA Med Ctr, Div Res, Charleston, SC 29401 USA.
C3 Free University of Berlin; Humboldt University of Berlin; Charite
   Universitatsmedizin Berlin; Berlin Institute of Health; Medical
   University of South Carolina; Ruprecht Karls University Heidelberg; Hans
   Knoll Institute (HKI); University of Munich; US Department of Veterans
   Affairs; Veterans Health Administration (VHA); Ralph H Johnson VA
   Medical Center
RP Strauss, O (通讯作者)，Charite Univ Med Berlin, Dept Ophthalmol, Berlin, Germany.; Rohrer, B (通讯作者)，Med Univ South Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.; Rohrer, B (通讯作者)，Ralph H Johnson VA Med Ctr, Div Res, Charleston, SC 29401 USA.
EM rohrer@musc.edu; olaf.strauss@charite.de
RI Strauss, Olaf/AAA-6485-2019
OI Strauss, Olaf/0000-0002-6272-8596
FU Charite - Universitatsmedizin Berlin; Berlin Institute of Health; Dr.
   Werner Jackstaedt Stiftung; Novartis; German Council "Deutsche
   Forschungsgemeinschaft" [SK46, SFB/Transregio 124]; National Institutes
   of Health (NIH) [R01EY019320, R01EY024581]; Department of Veterans
   Affairs [101 RX000444, BX003050]; SmartState Endowment; NATIONAL EYE
   INSTITUTE [R01EY024581] Funding Source: NIH RePORTER; Veterans Affairs
   [I01RX000444, I01BX003050] Funding Source: NIH RePORTER
FX The first author (CB) is participant in the Charlie Clinical Scientist
   Program funded by the Charite - Universitatsmedizin Berlin and the
   Berlin Institute of Health. YL is a doctoral researcher at the
   International Leibniz Research School (ILRS) and EJ of the Jena School
   of Microbial Communication (JSMC). The study is further supported by the
   Dr. Werner Jackstaedt Stiftung (OS), an unrestricted research grant by
   Novartis (OS), the German Council "Deutsche Forschungsgemeinschaft" SK46
   (YL, CS), the German Council "Deutsche Forschungsgemeinschaft"
   SFB/Transregio 124 funginet (EH, the National Institutes of Health (NIH)
   (R01EY019320 and R01EY024581) (BR), the Department of Veterans Affairs
   (101 RX000444 and BX003050) (BR), the SmartState Endowment (BR).
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NR 57
TC 18
Z9 18
U1 0
U2 1
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 JUN 15
PY 2017
VL 8
AR 703
DI 10.3389/fimmu.2017.00703
PG 14
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA EX5YS
UT WOS:000403319600001
PM 28663750
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Obert, E
   Strauss, R
   Brandon, C
   Grek, C
   Ghatnekar, G
   Gourdie, R
   Rohrer, B
AF Obert, Elisabeth
   Strauss, Randy
   Brandon, Carlene
   Grek, Christina
   Ghatnekar, Gautam
   Gourdie, Robert
   Rohrer, Barbel
TI Targeting the tight junction protein, zonula occludens-1, with the
   connexin43 mimetic peptide, alpha CT1, reduces VEGF-dependent RPE
   pathophysiology
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE Retinal pigment epithelium; Connexin43; Tight junctions; Choroidal
   neovascularization; Light damage; Vascular endothelial growth factor;
   Age-related macular degeneration
ID RETINAL-PIGMENT EPITHELIUM; DOMAIN-SWAPPED DIMERIZATION; 2ND PDZ DOMAIN;
   MACULAR DEGENERATION; CELL-LINE; CHOROIDAL NEOVASCULARIZATION; OCCLUDIN
   PHOSPHORYLATION; CARBOXYL-TERMINUS; ENDOTHELIAL-CELLS; OXIDATIVE STRESS
AB A critical target tissue in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), which forms the outer blood-retina barrier (BRB). RPE-barrier dysfunction might result from attenuation/disruption of intercellular tight junctions. Zonula occludens-1 (ZO-1) is a major structural protein of intercellular junctions. A connexin43-based peptide mimetic, alpha CT1, was developed to competitively block interactions at the PDZ2 domain of ZO-1, thereby inhibiting ligands that selectively bind to this domain. We hypothesized that targeting ZO-1 signaling using alpha CT1 would maintain BRB integrity and reduce RPE pathophysiology by stabilizing gap- and/or tight-junctions. RPE-cell barrier dysfunction was generated in mice using laser photocoagulation triggering choroidal neovascularization (CNV) or bright light exposure leading to morphological damage. alpha CT1 was delivered via eye drops. alpha CT1 treatment reduced CNV development and fluid leakage as determined by optical coherence tomography, and damage was correlated with disruption in cellular integrity of surrounding RPE cells. Light damage significantly disrupted RPE cell morphology as determined by ZO-1 and occludin staining and tiling pattern analysis, which was prevented by alpha CT1 pre-treatment. In vitro experiments using RPE and MDCK monolayers indicated that alpha CT1 stabilizes tight junctions, independent of its effects on Cx43. Taken together, stabilization of intercellular junctions by alpha CT1 was effective in ameliorating RPE dysfunction in models of AMD-like pathology.
C1 [Obert, Elisabeth; Rohrer, Barbel] Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA.
   [Strauss, Randy; Gourdie, Robert] Virginia Tech Caril Res Inst, Ctr Heart & Regenerat Med, Roanoke, VA 24016 USA.
   [Grek, Christina; Ghatnekar, Gautam] FirstString Res Inc, Mt Pleasant, SC 29464 USA.
   [Brandon, Carlene; Rohrer, Barbel] Med Univ South Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
   [Rohrer, Barbel] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA.
C3 Medical University of South Carolina; Medical University of South
   Carolina; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); Ralph H Johnson VA Medical Center
RP Rohrer, B (通讯作者)，Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA.; Rohrer, B (通讯作者)，Med Univ South Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.; Rohrer, B (通讯作者)，Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA.
EM rohrer@musc.edu
FU Feldberg Endowment; National Institutes of Health (NIH) [R01 EY019320,
   R01 HL56728]; Department of Veterans Affairs [I01 RX000444]; Foundation
   Fighting Blindness; Research to Prevent Blindness (RPB), Inc., New York,
   NY; FirstString Research, Inc. through NSF [IIP-1215149]; NIH [C06
   RR015455]; NATIONAL EYE INSTITUTE [R01EY019320] Funding Source: NIH
   RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL056728]
   Funding Source: NIH RePORTER; Veterans Affairs [I01BX003050,
   I01RX000444] Funding Source: NIH RePORTER
FX Funding for this project was provided in part by the Feldberg Endowment
   (BR), the National Institutes of Health (NIH) (R01 EY019320 to BR and
   R01 HL56728 to RGG), Department of Veterans Affairs (I01 RX000444),
   Foundation Fighting Blindness, an unrestricted grant to MUSC from
   Research to Prevent Blindness (RPB), Inc., New York, NY, as well as
   FirstString Research, Inc. (firststringresearch.com) (GSG, President and
   CEO; and CG, Director of Translational Research, both in advisory roles)
   through NSF grant IIP-1215149. No employees of FirstString Research were
   directly involved in study data collection; decision to publish and the
   writing of the manuscript (EO and BR). Animal studies were conducted in
   a facility constructed with support from the NIH (C06 RR015455).
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NR 86
TC 34
Z9 35
U1 0
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
EI 1432-1440
J9 J MOL MED
JI J. Mol. Med.
PD MAY
PY 2017
VL 95
IS 5
BP 535
EP 552
DI 10.1007/s00109-017-1506-8
PG 18
WC Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Research & Experimental Medicine
GA EV8FK
UT WOS:000402015900008
PM 28132078
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Thumann, G
   Harmening, N
   Prat-Souteyrand, C
   Marie, C
   Pastor, M
   Sebe, A
   Miskey, C
   Hurst, LD
   Diarra, S
   Kropp, M
   Walter, P
   Scherman, D
   Ivics, Z
   Izsvak, Z
   Johnen, S
AF Thumann, Gabriele
   Harmening, Nina
   Prat-Souteyrand, Cecile
   Marie, Corinne
   Pastor, Marie
   Sebe, Attila
   Miskey, Csaba
   Hurst, Laurence D.
   Diarra, Sabine
   Kropp, Martina
   Walter, Peter
   Scherman, Daniel
   Ivics, Zoltan
   Izsvak, Zsuzsanna
   Johnen, Sandra
TI Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the
   SB Transposon System Delivered by pFAR4 Plasmids
SO MOLECULAR THERAPY-NUCLEIC ACIDS
LA English
DT Article
ID SLEEPING-BEAUTY TRANSPOSITION; GENE-TRANSFER; MACULAR DEGENERATION;
   TRANSGENE EXPRESSION; PURIFYING SELECTION; PIGGYBAC TRANSPOSON; SITE
   SELECTION; DNA SIZE; VECTOR; TRANSPLANTATION
AB Neovascular age-related macular degeneration (nvAMD) is characterized by choroidal blood vessels growing into the sub-retinal space, leading to retinal pigment epithelial (RPE) cell degeneration and vision loss. Vessel growth results from an imbalance of pro-angiogenic (e.g., vascular endothelial growth factor [VEGF]) and anti-angiogenic factors (e.g., pigment epithelium-derived factor [PEDF]). Current treatment using intravitreal injections of anti-VEGF antibodies improves vision in about 30% of patients but may be accompanied by side effects and non-compliance. To avoid the difficulties posed by frequent intravitreal injections, we have proposed the transplantation of pigment epithelial cells modified to overexpress human PEDF. Stable transgene integration and expression is ensured by the hyperactive Sleeping Beauty transposon system delivered by pFAR4 miniplasmids, which have a backbone free of antibiotic resistance markers. We demonstrated efficient expression of the PEDF gene and an optimized PEDF cDNA sequence in as few as 5 x 10(3) primary cells. At 3 weeks post-transfection, PEDF secretion was significantly elevated and long-term follow-up indicated a more stable secretion by cells transfected with the optimized PEDF transgene. Analysis of transgene insertion sites in human RPE cells showed an almost random genomic distribution. The results represent an important contribution toward a clinical trial aiming at a non-viral gene therapy of nvAMD.
C1 [Thumann, Gabriele] Univ Hosp Geneva, Dept Ophthalmol, 22 Rue Alcide Jentzer, CH-1205 Geneva, Switzerland.
   [Thumann, Gabriele; Harmening, Nina; Prat-Souteyrand, Cecile; Kropp, Martina] Univ Geneva, Lab Ophthalmol, CH-1205 Geneva, Switzerland.
   [Marie, Corinne; Pastor, Marie; Scherman, Daniel] CNRS, Unite Technol Chim & Biol Sante UMR 8258, F-75006 Paris, France.
   [Marie, Corinne; Pastor, Marie; Scherman, Daniel] Univ Paris 05, Sorbonne Paris Cite, UTCBS, F-75006 Paris, France.
   [Marie, Corinne; Pastor, Marie; Scherman, Daniel] INSERM, UTCBS U 1022, F-75006 Paris, France.
   [Marie, Corinne; Pastor, Marie; Scherman, Daniel] PSL Res Univ, UTCBS, Chim ParisTech, F-75005 Paris, France.
   [Sebe, Attila; Miskey, Csaba; Ivics, Zoltan] Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany.
   [Hurst, Laurence D.] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England.
   [Diarra, Sabine; Walter, Peter; Johnen, Sandra] Univ Hosp RWTH Aachen, Dept Ophthalmol, D-52074 Aachen, Germany.
   [Izsvak, Zsuzsanna] Max Delbruck Ctr Mol Med Helmholtz Assoc, D-13092 Berlin, Germany.
C3 University of Geneva; University of Geneva; Centre National de la
   Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC);
   UDICE-French Research Universities; Universite Paris Cite; UDICE-French
   Research Universities; Universite Paris Cite; Institut National de la
   Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Universite Paris Cite; UDICE-French Research Universities;
   PSL Research University Paris; Chimie ParisTech; Universite Paris Cite;
   Paul Ehrlich Institute; University of Bath; RWTH Aachen University; RWTH
   Aachen University Hospital; Helmholtz Association; Max Delbruck Center
   for Molecular Medicine
RP Thumann, G (通讯作者)，Univ Hosp Geneva, Dept Ophthalmol, 22 Rue Alcide Jentzer, CH-1205 Geneva, Switzerland.
EM gabriele.thumann@hcuge.ch
RI Sebe, Attila/K-2644-2017; Miskey, Csaba/U-3473-2017; Harmening,
   Nina/F-7804-2017; Walter, Peter/L-5982-2018; Johnen,
   Sandra/ABA-9955-2020; Sebe, Attila/GXV-5092-2022; Hurst,
   Laurence/F-9215-2010; Kropp, Martina/H-9260-2018
OI Sebe, Attila/0000-0001-7814-5144; Walter, Peter/0000-0001-8745-6593;
   Johnen, Sandra/0000-0003-0028-2557; Sebe, Attila/0000-0001-7814-5144;
   Hurst, Laurence/0000-0002-1002-1054; Scherman,
   Daniel/0000-0003-1207-1298; Kropp, Martina/0000-0001-6861-5851; MARIE,
   Corinne/0000-0001-9619-5700
FU European Union [305134]; Center for Cell and Gene Therapy of the LOEWE
   (Landes-Offensive zur Entwicklung Wissenschaftlich-okonomischer
   Exzellenz) program in Hessen, Germany; European Research Council
   [ERC-2014-ADG 669207]; Medical Research Council [MR/L007215/1]; MRC
   [MR/L007215/1] Funding Source: UKRI
FX This work was supported by the European Union's Seventh Framework
   Programme for research, technological development and demonstration,
   grant agreement no. 305134. C. Miskey and Z. Ivics were supported by the
   Center for Cell and Gene Therapy of the LOEWE (Landes-Offensive zur
   Entwicklung Wissenschaftlich-okonomischer Exzellenz) program in Hessen,
   Germany. L.D.H. was supported by the European Research Council (advanced
   grant ERC-2014-ADG 669207) and the Medical Research Council
   (MR/L007215/1). The authors thank Anna Dobias, Antje Schiefer
   (Department of Ophthalmology, University Hospital RWTH Aachen), Gregg
   Sealy (Laboratory of Ophthalmology, University of Geneva) for excellent
   technical support, the Aachen Cornea Bank (Department of Ophthalmology,
   University Hospital RWTH Aachen) for providing the human donor eyes, and
   Perry B. Hackett (Center for Genome Engineering, The University of
   Minnesota) for the gift of pT2/BH.
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NR 62
TC 21
Z9 21
U1 3
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 2162-2531
J9 MOL THER-NUCL ACIDS
JI Mol. Ther.-Nucl. Acids
PD MAR 17
PY 2017
VL 6
BP 302
EP 314
DI 10.1016/j.omtn.2017.02.002
PG 13
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA EP0QP
UT WOS:000397092100027
PM 28325297
OA Green Published, gold, Green Accepted
DA 2022-11-30
ER

PT J
AU Rossi, EA
   Granger, CE
   Sharma, R
   Yang, Q
   Saito, K
   Schwarz, C
   Walters, S
   Nozato, K
   Zhang, J
   Kawakami, T
   Fischer, W
   Latchney, LR
   Hunter, JJ
   Chung, MM
   Williams, DR
AF Rossi, Ethan A.
   Granger, Charles E.
   Sharma, Robin
   Yang, Qiang
   Saito, Kenichi
   Schwarz, Christina
   Walters, Sarah
   Nozato, Koji
   Zhang, Jie
   Kawakami, Tomoaki
   Fischer, William
   Latchney, Lisa R.
   Hunter, Jennifer J.
   Chung, Mina M.
   Williams, David R.
TI Imaging individual neurons in the retinal ganglion cell layer of the
   living eye
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE imaging; adaptive optics; retinal ganglion cells; photoreceptors; retina
ID ADAPTIVE OPTICS; AMACRINE CELLS; LASER; CONE; FIELD; TOMOGRAPHY;
   RESOLUTION; PARASOL; VISION; RODS
AB Although imaging of the living retina with adaptive optics scanning light ophthalmoscopy (AOSLO) provides microscopic access to individual cells, such as photoreceptors, retinal pigment epithelial cells, and blood cells in the retinal vasculature, other important cell classes, such as retinal ganglion cells, have proven much more challenging to image. The near transparency of inner retinal cells is advantageous for vision, as light must pass through them to reach the photoreceptors, but it has prevented them from being directly imaged in vivo. Here we show that the individual somas of neurons within the retinal ganglion cell (RGC) layer can be imaged with a modification of confocal AOSLO, in both monkeys and humans. Human images of RGC layer neurons did not match the quality of monkey images for several reasons, including safety concerns that limited the light levels permissible for human imaging. We also show that the same technique applied to the photoreceptor layer can resolve ambiguity about cone survival in age-related macular degeneration. The capability to noninvasively image RGC layer neurons in the living eye may one day allow for a better understanding of diseases, such as glaucoma, and accelerate the development of therapeutic strategies that aim to protect these cells. This method may also prove useful for imaging other structures, such as neurons in the brain.
C1 [Rossi, Ethan A.; Granger, Charles E.; Sharma, Robin; Yang, Qiang; Schwarz, Christina; Walters, Sarah; Zhang, Jie; Hunter, Jennifer J.; Chung, Mina M.; Williams, David R.] Univ Rochester, Ctr Visual Sci, 601 Elmwood Ave, Rochester, NY 14642 USA.
   [Granger, Charles E.; Walters, Sarah; Williams, David R.] Univ Rochester, Inst Opt, Rochester, NY 14620 USA.
   [Saito, Kenichi; Nozato, Koji; Kawakami, Tomoaki] Canon USA Inc, Melville, NY 11747 USA.
   [Fischer, William; Latchney, Lisa R.; Hunter, Jennifer J.; Chung, Mina M.] Univ Rochester, Med Ctr, Flaum Eye Inst, Rochester, NY 14642 USA.
   [Rossi, Ethan A.] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15213 USA.
C3 University of Rochester; University of Rochester; Canon Incorporated;
   University of Rochester; Pennsylvania Commonwealth System of Higher
   Education (PCSHE); University of Pittsburgh
RP Rossi, EA (通讯作者)，Univ Rochester, Ctr Visual Sci, 601 Elmwood Ave, Rochester, NY 14642 USA.; Rossi, EA (通讯作者)，Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15213 USA.
EM rossiea@pitt.edu
RI Rossi, Ethan/A-7933-2013; Rossi, Ethan/AAC-6204-2019
OI Rossi, Ethan/0000-0003-3210-0551; Rossi, Ethan/0000-0003-3210-0551;
   Hunter, Jennifer/0000-0001-5801-4737; Schwarz,
   Christina/0000-0003-0796-9773; Williams, David R/0000-0003-3227-8333
FU NIH [EY021786, EY001319, EY014375, EY004367, EY022371, AG043645,
   EY007125, EY025497]; Canon, Inc.; Edward N. & Della L. Thome Memorial
   Foundation; Research to Prevent Blindness; NATIONAL EYE INSTITUTE
   [R01EY022371, U01EY025497, R01EY021786, R01EY004367, P30EY001319,
   T32EY007125, R01EY014375] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE ON AGING [R44AG043645] Funding Source: NIH RePORTER
FX This work was funded by NIH Grants EY021786, EY001319, EY014375,
   EY004367, EY022371, AG043645, EY007125, and EY025497; a grant from
   Canon, Inc.; a grant from the Edward N. & Della L. Thome Memorial
   Foundation (to M.M.C.); and a grant to the University of Rochester
   Department of Ophthalmology from Research to Prevent Blindness.
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NR 54
TC 105
Z9 108
U1 0
U2 24
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 17
PY 2017
VL 114
IS 3
BP 586
EP 591
DI 10.1073/pnas.1613445114
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EH9MQ
UT WOS:000392095800052
PM 28049835
OA Green Published
DA 2022-11-30
ER

PT J
AU Masuda, T
   Shimazawa, M
   Takata, S
   Nakamura, S
   Tsuruma, K
   Hara, H
AF Masuda, Tomomi
   Shimazawa, Masamitsu
   Takata, Shinsuke
   Nakamura, Shinsuke
   Tsuruma, Kazuhiro
   Hara, Hideaki
TI Edaravone is a free radical scavenger that protects against
   laser-induced choroidal neovascularization in mice and common marmosets
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Laser-induced choroidal neovascularization model; Edaravone; Free
   radical scavenger; Common marmosets; 4-hydroxy-2-nonenal; Reactive
   oxygen species; Human retinal microvascular endothelial cells; Human
   retinal pigment epithelium cells
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; OXIDATIVE STRESS;
   POSSIBLE INVOLVEMENT; CEREBRAL-ISCHEMIA; CIGARETTE-SMOKE; RETINAL
   DAMAGE; ANIMAL-MODELS; UP-REGULATION; IN-VITRO
AB Choroidal neovascularization (CNV) is a main characteristic in exudative type of age-related macular degeneration (AMD). Our study aimed to evaluate the effects of edaravone, a free radical scavenger on laser-induced CNV. CNV was induced by laser photocoagulation to the subretinal choroidal area of mice and common marmosets. Edaravone was administered either intraperitoneally twice a day for 2 weeks or intravenously just once after laser photocoagulation. The effects of edaravone on laser-induced CNV were evaluated by fundus fluorescein angiography, CNV area measurements, and the expression of 4-hydroxy-2-nonenal (4-HNE) modified proteins, a marker of oxidative stress. Furthermore, the effects of edaravone on the production of H2O2-induced reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF)-induced cell proliferation were evaluated using human retinal pigment epithelium cells (ARPE-19) and human retinal microvascular endothelial cells, respectively. CNV areas in the edaravone-treated group were significantly smaller in mice and common marmosets. The expression of 4-HNE modified proteins was upregulated 3 h after laser photocoagulation, and intravenously administered edaravone decreased it. In in vitro studies, edaravone inhibited H2O2-induced ROS production and VEGF-induced cell proliferation. These findings suggest that edaravone may protect against laser-induced CNV by inhibiting oxidative stress and endothelial cell proliferation. (c) 2016 Elsevier Ltd. All rights reserved.
C1 [Masuda, Tomomi; Shimazawa, Masamitsu; Takata, Shinsuke; Nakamura, Shinsuke; Tsuruma, Kazuhiro; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
C3 Gifu Pharmaceutical University
RP Shimazawa, M (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
EM shimazawa@gifu-pu.ac.jp
OI Hara, Hideaki/0000-0003-2046-9001
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NR 62
TC 17
Z9 19
U1 1
U2 10
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 MAY
PY 2016
VL 146
BP 196
EP 205
DI 10.1016/j.exer.2016.03.020
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DM4QS
UT WOS:000376332400024
PM 27018216
DA 2022-11-30
ER

PT J
AU Chen, L
   Kim, IK
   Lane, AM
   Gauthier, D
   Munzenrider, JE
   Gragoudas, ES
   Miller, JW
AF Chen, Ling
   Kim, Ivana K.
   Lane, Anne M.
   Gauthier, Danny
   Munzenrider, John E.
   Gragoudas, Evangelos S.
   Miller, Joan W.
TI Proton beam irradiation for non-AMD CNV: 2-year results of a randomised
   clinical trial
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; INTRAVITREAL BEVACIZUMAB
   AVASTIN; MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; PATHOLOGICAL
   MYOPIA; ANGIOID STREAKS; MULTIFOCAL CHOROIDITIS; RADIATION-THERAPY;
   VERTEPORFIN; SECONDARY
AB Aims To evaluate safety and visual outcomes after proton beam irradiation (PBI) therapy for subfoveal choroidal neovascularisation (CNV) secondary to causes other than age-related macular degeneration (AMD).
   Methods This study is a prospective, unmasked and randomised clinical trial using two dosage regimens, conducted in the Massachusetts Eye and Ear Infirmary. The study included 46 patients with CNV secondary to non-AMD and best-corrected visual acuity of 20/320 or better. Patients were randomly assigned to receive 16 or 24 cobalt gray equivalents (CGE) of PBI in two equal fractions. Complete ophthalmological examinations, fundus photography and fluorescein angiography were performed at baseline and 6, 12, 18 and 24 months after treatment.
   Results At 1 year after treatment, 82% and 72% lost fewer than 1.5 lines of vision in the 16 CGE and in 24 CGE groups, respectively. At 2 years after therapy, 77% in the lower dose group and 64% in the higher dose group lost fewer than 1.5 lines of vision. Mild radiation complications such as radiation vasculopathy developed in 17.6% of patients.
   Conclusions PBI is a safe and efficacious treatment for subfoveal CNV not due to AMD. The data with respect to visual outcomes and radiation complications trend in favour of the 16 CGE group, although differences do not reach statistical significance. PBI may be considered as an alternative to current therapies.
C1 [Chen, Ling; Kim, Ivana K.; Lane, Anne M.; Gragoudas, Evangelos S.; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA USA.
   [Chen, Ling] Univ Hong Kong, Dept Ophthalmol, Hong Kong, Hong Kong, Peoples R China.
   [Chen, Ling] Fudan Univ, Shanghai Med Sch, Eye & ENT Hosp, Dept Ophthalmol & Vis Sci, Shanghai 200433, Peoples R China.
   [Gauthier, Danny] Univ Montreal, Hop Notre Dame, Dept Ophthalmol, Retina Serv, Montreal, PQ, Canada.
   [Munzenrider, John E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; University of Hong Kong; Fudan University; Universite de
   Montreal; Harvard University; Harvard Medical School; Massachusetts
   General Hospital
RP Miller, JW (通讯作者)，Massachusetts Eye & Ear Infirm, Chair Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM joan_miller@meei.harvard.edu
RI Chen, Ling/AAM-1821-2021
OI Kim, Ivana/0000-0003-0310-6129; Miller, Joan/0000-0003-2046-3996
FU National Natural Science Foundation of China [81000381, 81371042]; major
   programme of the Natural Science Foundation of China [2013CB967503];
   Scientific Research Starting Foundation for the Returned Overseas
   Chinese Scholars, Ministry of Education; Retina Research Fund of
   Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; Melanoma
   Research Fund of Massachusetts Eye and Ear Infirmary, Boston,
   Massachusetts; Neovascular Research Fund of Massachusetts Eye and Ear
   Infirmary, Boston, Massachusetts; Macula Foundation, New York, New York
FX LC is sponsored by the National Natural Science Foundation of China
   (grant no. 81000381, 81371042), the major programme of the Natural
   Science Foundation of China (grant no. 2013CB967503) and the Scientific
   Research Starting Foundation for the Returned Overseas Chinese Scholars,
   Ministry of Education. The study was supported by the Retina Research
   Fund, Melanoma Research Fund, and Neovascular Research Fund of
   Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; and the
   Macula Foundation, New York, New York.
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NR 30
TC 4
Z9 4
U1 0
U2 10
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 2014
VL 98
IS 9
BP 1212
EP 1217
DI 10.1136/bjophthalmol-2013-304761
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AN3QW
UT WOS:000340504400013
PM 24820046
DA 2022-11-30
ER

PT J
AU Hou, YZ
   Lin, HJ
   Zhu, LN
   Liu, ZT
   Hu, FL
   Shi, JF
   Yang, T
   Shi, XY
   Guo, HF
   Tan, XT
   Zhang, LF
   Wang, Q
   Li, ZG
   Zhao, Y
AF Hou, Yuzhu
   Lin, Haijiang
   Zhu, Linnan
   Liu, Zhaoting
   Hu, Fanlei
   Shi, Jianfeng
   Yang, Tao
   Shi, Xiaoyun
   Guo, Huifang
   Tan, Xiaotian
   Zhang, Lianfeng
   Wang, Qiang
   Li, Zhanguo
   Zhao, Yong
TI The Inhibitory Effect of IFN-gamma on Protease HTRA1 Expression in
   Rheumatoid Arthritis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID COLLAGEN-INDUCED ARTHRITIS; SERINE-PROTEASE; MICE; MACROPHAGES;
   DEFICIENT; CARTILAGE; GENE; LPS; SUSCEPTIBILITY; INDUCTION
AB The high temperature requirement A1 (HTRA1) is a potent protease involved in many diseases, including rheumatoid arthritis (RA). However, the regulatory mechanisms that control HTRA1 expression need to be determined. In this study, we demonstrated that IFN-gamma significantly inhibited the basal and LPS-induced HTRA1 expression in fibroblasts and macrophages, which are two major cells for HTRA1 production in RA. Importantly, the inhibitory effect of IFN-gamma on HTRA1 expression was evidenced in collagen-induced arthritis (CIA) mouse models and in human RA synovial cells. In parallel with the enhanced CIA incidence and pathological changes in IFN-gamma-deficient mice, HTRA1 expression in the joint tissues was also increased as determined by real-time PCR and Western blots. IFN-gamma deficiency increased the incidence of CIA and the pathological severity in mice. Neutralization of HTRA1 by Ab significantly reversed the enhanced CIA frequency and severity in IFN-gamma-deficient mice. Mechanistically, IFN-gamma negatively controls HTRA1 expression through activation of p38 MAPK/STAT1 pathway. Dual luciferase reporter assay and chromatin immunoprecipitation analysis showed that STAT1 could directly bind to HTRA1 promoter after IFN-gamma stimulation. This study offers new insights into the molecular regulation of HTRA1 expression and its role in RA pathogenesis, which may have significant impact on clinical therapy for RA and possibly other HTRA1-related diseases, including osteoarthritis, age-related macular degeneration, and cancer.
C1 [Hou, Yuzhu; Zhu, Linnan; Liu, Zhaoting; Shi, Jianfeng; Yang, Tao; Shi, Xiaoyun; Tan, Xiaotian; Wang, Qiang; Zhao, Yong] Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China.
   [Hou, Yuzhu; Zhu, Linnan; Shi, Jianfeng; Yang, Tao; Zhao, Yong] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
   [Lin, Haijiang] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
   [Hu, Fanlei; Li, Zhanguo] Peking Univ, Peoples Hosp, Clin Immunol Ctr, Dept Rheumatol & Immunol, Beijing 100044, Peoples R China.
   [Shi, Xiaoyun] Chinese Peoples Armed Police Forces, Gen Hosp, Beijing 100039, Peoples R China.
   [Guo, Huifang] Hebei Med Univ, Hosp 2, Dept Rheumatol, Shijiazhuang 050000, Peoples R China.
   [Zhang, Lianfeng] Chinese Acad Med Sci, Minist Hlth, Key Lab Human Dis Comparat Med, Beijing 100021, Peoples R China.
   [Zhang, Lianfeng] Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing 100021, Peoples R China.
   Peking Union Med Coll, Beijing 100021, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Zoology, CAS; Chinese Academy
   of Sciences; University of Chinese Academy of Sciences, CAS; Harvard
   University; Harvard Medical School; Massachusetts Eye & Ear Infirmary;
   Peking University; Hebei Medical University; Chinese Academy of Medical
   Sciences - Peking Union Medical College; Chinese Academy of Medical
   Sciences - Peking Union Medical College; Institute of Laboratory Animal
   Science - CAMS; Chinese Academy of Medical Sciences - Peking Union
   Medical College; Peking Union Medical College
RP Zhao, Y (通讯作者)，Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Transplantat Biol Res Div, Beichen West Rd 1-5, Beijing 100101, Peoples R China.
EM qiangwang@ioz.ac.cn; zgli@yahoo.com; zhaoy@ioz.ac.cn
RI Hou, Yuzhu/O-2035-2019
OI Hou, Yuzhu/0000-0001-8274-027X; Lin, Haijiang/0000-0003-2931-468X; Wang,
   Qiang/0000-0002-8735-8771
FU National Basic Research Program of China [2010CB945301, 2011CB710900,
   2010CB529100]; National Natural Science Foundation of China [C81130055,
   U0832003]; Knowledge Innovation Program of Chinese Academy of Sciences
   [YSCX2-YW-238]; State Administration of Foreign Experts Affairs of
   Chinese Academy of Sciences International Partnership Program for
   Creative Research Teams
FX This work was supported by National Basic Research Program of China
   Grants 2010CB945301, 2011CB710900 (to Y.Z.), and 2010CB529100 (to Z.
   Li), National Natural Science Foundation of China for General and Key
   Programs Grants C81130055 and U0832003 (to Y.Z.), Knowledge Innovation
   Program of Chinese Academy of Sciences Grant YSCX2-YW-238 (to Y.Z.), as
   well as by the State Administration of Foreign Experts Affairs of
   Chinese Academy of Sciences International Partnership Program for
   Creative Research Teams (to Y.Z.).
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NR 44
TC 29
Z9 31
U1 0
U2 15
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUL 1
PY 2014
VL 193
IS 1
BP 130
EP 138
DI 10.4049/jimmunol.1302700
PG 9
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA AK5BN
UT WOS:000338438900018
PM 24907345
OA Bronze
DA 2022-11-30
ER

PT J
AU Rodriguez, E
   Rallapalli, PM
   Osborne, AJ
   Perkins, SJ
AF Rodriguez, Elizabeth
   Rallapalli, Pavithra M.
   Osborne, Amy J.
   Perkins, Stephen J.
TI New functional and structural insights from updated mutational databases
   for complement factor H, Factor I, membrane cofactor protein and C3
SO BIOSCIENCE REPORTS
LA English
DT Article
DE age-related macular degeneration; alternative pathway; atypical
   haemolytic uraemic syndrome; complement structure; immunodeficiency
   diseases; mutation database
ID HEMOLYTIC-UREMIC SYNDROME; MOLECULAR-BASIS; SELF-ASSOCIATION; SECONDARY
   STRUCTURE; HEPARAN-SULFATE; HIGH-RISK; GENE; VARIANT; RARE; CD46
AB aHUS (atypical haemolytic uraemic syndrome), AMD (age-related macular degeneration) and other diseases are associated with defective AP (alternative pathway) regulation. CFH (complement factor H), CFI (complement factor I), MCP (membrane cofactor protein) and C3 exhibited the most disease-associated genetic alterations in the AP. Our interactive structural database for these was updated with a total of 324 genetic alterations. A consensus structure for the SCR (short complement regulator) domain showed that the majority (37%) of SCR mutations occurred at its hypervariable loop and its four conserved Cys residues. Mapping 113 missense mutations onto the CFH structure showed that over half occurred in the C-terminal domains SCR-15 to -20. In particular, SCR-20 with the highest total of affected residues is associated with binding to C3d and heparin-like oligosaccharides. No clustering of 49 missense mutations in CFI was seen. In MCP, SCR-3 was the most affected by 23 missense mutations. In C3, the neighbouring thioester and MG (macroglobulin) domains exhibited most of 47 missense mutations. The mutations in the regulators CFH, CFI and MCP involve loss-of-function, whereas those for C3 involve gain-of-function. This combined update emphasizes the importance of the complement AP in inflammatory disease, clarifies the functionally important regions in these proteins, and will facilitate diagnosis and therapy.
C1 [Rodriguez, Elizabeth; Rallapalli, Pavithra M.; Osborne, Amy J.; Perkins, Stephen J.] UCL, Dept Biol Mol & Struct, London WC1E 6BT, England.
C3 University of London; University College London
RP Perkins, SJ (通讯作者)，UCL, Dept Biol Mol & Struct, Darwin Bldg,Gower St, London WC1E 6BT, England.
EM s.perkins@ucl.ac.uk
OI Osborne, Amy/0000-0001-6869-1176; Rallapalli,
   Pavithra/0000-0002-8261-6209
FU Centre for Molecular Structures and Dynamics of the Science and
   Technology Facilities Council; Engineering and Physical Science Research
   Council; Pfizer U.K.; Royal Free Hospital; Katharine Dormandy Trust for
   Haemophilia and Related Disorders; European Association for Haemophilia
   and Associated Disorders; Complement UK
FX This work was supported by the Centre for Molecular Structures and
   Dynamics of the Science and Technology Facilities Council and the
   Engineering and Physical Science Research Council (to E. R.), Pfizer
   U.K., the Special Trustees of the Royal Free Hospital, the Katharine
   Dormandy Trust for Haemophilia and Related Disorders, and the European
   Association for Haemophilia and Associated Disorders (to P. M. R.), and
   Complement UK (to A.J.O.).
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NR 95
TC 50
Z9 53
U1 0
U2 8
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0144-8463
EI 1573-4935
J9 BIOSCIENCE REP
JI Biosci. Rep.
PY 2014
VL 34
BP 635
EP 649
AR e00146
DI 10.1042/BSR20140117
PN 5
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA AS8CW
UT WOS:000344478800012
PM 25188723
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Amoaku, W
   Blakeney, S
   Freeman, M
   Gale, R
   Johnston, R
   Kelly, SP
   McLaughlan, B
   Sahu, D
   Varma, D
AF Amoaku, W.
   Blakeney, S.
   Freeman, M.
   Gale, R.
   Johnston, R.
   Kelly, S. P.
   McLaughlan, B.
   Sahu, D.
   Varma, D.
CA Action AMD Grp
TI Action on AMD. Optimising patient management: act now to ensure current
   and continual delivery of best possible patient care
SO EYE
LA English
DT Review
DE age-related macular degeneration; anti-VEGF therapy; commissioning;
   health-care facilities; manpower; services
ID VISION-RELATED FUNCTION; RANDOMIZED CLINICAL-TRIAL; MACULAR
   DEGENERATION; PHOTODYNAMIC THERAPY; RANIBIZUMAB TREATMENT; VERTEPORFIN;
   ENGLAND; ANCHOR; WALES
AB In recent years, there have been significant advances in the clinical management of patients with wet age-related macular degeneration (wet AMD)-a rapidly progressing and potentially blinding degenerative eye disease. Wet AMD is responsible for more than half of registered severe sight impairment (blindness) in the United Kingdom, and patients who are being treated for wet AMD require frequent and long-term follow-up for treatment to be most effective. The clinical workload associated with the frequent follow-up required is substantial. Furthermore, as more new patients are diagnosed and the population continues to age, the patient population will continue to increase. It is thus vital that clinical services continue to adapt so that they can provide a fast and efficient service for patients with wet AMD. This Action on AMD document has been developed by eye health-care professionals and patient representatives, the Action on AMD group. It is intended to highlight the urgent and continuing need for change within wet AMD services. This document also serves as a guide for eye health-care professionals, NHS commissioners, and providers to present possible solutions for improving NHS retinal and macular services. Examples of good practice and service development are considered and can be drawn upon to help services meet the recommended quality of care and achieve best possible outcomes. Eye (2012) 26, S2-S21; doi:10.1038/eye.2011.343
C1 [Amoaku, W.] Univ Hosp, QMC, Eye & ENT Ctr, Nottingham NG7 2UH, England.
   [Blakeney, S.] BP Eyecare Ltd, London, Kent, England.
   [Freeman, M.] Royal Hallamshire Hosp, Sheffield S10 2JF, S Yorkshire, England.
   [Gale, R.] York Teaching Hosp, York, N Yorkshire, England.
   [Johnston, R.] Cheltenham Gen Hosp, Cheltenham, Glos, England.
   [Kelly, S. P.] Royal Bolton Hosp, Bolton, Lancs, England.
   [McLaughlan, B.] Royal Natl Inst Blind People, London, England.
   [Sahu, D.] Southampton Gen Hosp, Southampton SO9 4XY, Hants, England.
   [Varma, D.] Sunderland Eye Infirm, Sunderland, Tyne & Wear, England.
C3 Nottingham University Hospital NHS Trust; University of Nottingham; BP;
   University of Sheffield; Gloucestershire Hospitals NHS Foundation Trust;
   Cheltenham General Hospital; Royal Bolton Hospital; University of
   Southampton
RP Amoaku, W (通讯作者)，Univ Hosp, QMC, Eye & ENT Ctr, Nottingham NG7 2UH, England.
EM Winfried.Amoaku@nottingham.ac.uk
OI Amoaku, Winfried/0000-0001-5028-7984
FU Novartis Pharmaceuticals
FX An expert capacity working group was formed in May 2010, and support for
   initial meeting expenses and logistics was provided by Novartis. A
   report was generated by the meeting, which formed the basis of this
   document. Novartis has had the opportunity to review this document for
   technical accuracy but has had no editorial input. We thank Sue Harris
   from ApotheCom who provided medical writing support on behalf of
   Novartis Pharmaceuticals.
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NR 25
TC 33
Z9 34
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD FEB
PY 2012
VL 26
SU 1
BP S2
EP S21
DI 10.1038/eye.2011.343
PG 20
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 893ZJ
UT WOS:000300396200001
PM 22302094
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Karlstetter, M
   Ebert, S
   Langmann, T
AF Karlstetter, Marcus
   Ebert, Stefanie
   Langmann, Thomas
TI Microglia in the healthy and degenerating retina: Insights from novel
   mouse models
SO IMMUNOBIOLOGY
LA English
DT Article
DE Retinal degeneration; Microglia; Mouse models; EGFP reporters
ID MARROW-DERIVED MICROGLIA; RETINOSCHISIN-DEFICIENT RETINA; MACULAR
   DEGENERATION; SUBRETINAL MICROGLIA; ACTIVATED MICROGLIA; MACROPHAGE
   LINEAGE; ALZHEIMERS-DISEASE; DENDRITIC CELLS; TGF-BETA; IN-VIVO
AB In contrast to the tremendous amount of research data from the central nervous system, relatively little is known about microglial homeostasis in the retina. This may be explained by a strong research bias towards important brain pathologies including Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis. In addition, there are specific technical limitations which hampered the analysis of retinal microglia, including their relatively small number in ocular tissue. The lack of experimental tools also prevented direct visualization and molecular analysis of this specialized neuronal macrophage population. Over the last few years, this situation has changed considerably as more and more retinal disorders have come into focus. Many rare monogenic forms as well as more prevalent complex disorders, in particular the age-related macular degeneration involves innate immune mechanisms. As a consequence, new genetic and experimental mouse models have been developed that mimic various forms of human retinal degeneration. In conjunction with these disease models, novel macrophage/microglia-specific reporter mice were established that allow the monitoring of retinal microglia in situ and in vivo. This review summarizes recent findings from these mouse models and thereby provides an overview of microglial homeostasis in the healthy and degenerating retina. Based on this knowledge, microglia-targeted therapies are envisioned which could delay or attenuate degenerative retinal disease. (C) 2010 Elsevier GmbH. All rights reserved.
C1 [Karlstetter, Marcus; Ebert, Stefanie; Langmann, Thomas] Univ Regensburg, Inst Human Genet, Regensburg, Germany.
C3 University of Regensburg
RP Langmann, T (通讯作者)，Univ Regensburg, Inst Human Genet, Regensburg, Germany.
EM thomas.langmann@klinik.uni-regensburg.de
FU German Research Foundation [LA1203/7-4]; Elite Network of Bavaria; Pro
   Retina Foundation
FX We would like to acknowledge the contributions of the scientists whose
   work was not cited here. Some included references are review articles
   and the reader is directed to them especially for articles published
   before 2007. We thank Bernhard Weber and Michael Rehli for critical
   reading the manuscript. Our group is supported by grants from the German
   Research Foundation (FOR1075 Project 4, LA1203/7-4), the Elite Network
   of Bavaria, and the Pro Retina Foundation.
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   Xu HP, 2008, AGING CELL, V7, P58, DOI 10.1111/j.1474-9726.2007.00351.x
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NR 76
TC 150
Z9 154
U1 0
U2 20
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0171-2985
J9 IMMUNOBIOLOGY
JI Immunobiology
PD SEP-OCT
PY 2010
VL 215
IS 9-10
SI SI
BP 685
EP 691
DI 10.1016/j.imbio.2010.05.010
PG 7
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 646JT
UT WOS:000281536800003
PM 20573418
DA 2022-11-30
ER

PT J
AU Qiu, Y
   Hoareau-Aveilla, C
   Oltean, S
   Harper, SJ
   Bates, DO
AF Qiu, Yan
   Hoareau-Aveilla, Coralie
   Oltean, Sebastian
   Harper, Steven J.
   Bates, David O.
TI The anti-angiogenic isoforms of VEGF in health and disease
SO BIOCHEMICAL SOCIETY TRANSACTIONS
LA English
DT Article
DE angiogenesis; carcinoma sample; Denys-Drash syndrome; human vitreous
   fluid; rheumatoid arthritis; vasculogenesis
ID ENDOTHELIAL GROWTH-FACTOR; SPLICE VARIANT; CORPUS-LUTEUM; MESSENGER-RNA;
   IN-VIVO; MACULAR DEGENERATION; DIABETIC-RETINOPATHY; RECEPTOR
   EXPRESSION; TUMOR-GROWTH; A ISOFORM
AB Anti-angiogenic VEGF (vascular endothelial growth factor) isoforms, generated from differential splicing of exon 8, are widely expressed in normal human tissues but down-regulated in cancers and other pathologies associated with abnormal angiogenesis (cancer, diabetic retinopathy, retinal vein occlusion, the Denys-Drash syndrome and pre-eclampsia). Administration of recombinant VEGF(165)b inhibits ocular angiogenesis in mouse models of retinopathy and age-related macular degeneration, and colorectal carcinoma and metastatic melanoma. Splicing factors and their regulatory molecules alter splice site selection, such that cells can switch from the anti-angiogenic VEGF(xxx)b isoforms to the pro-angiogenic VEGF(xxx) isoforms, including Si (serine/arginine protein SS), ASF/SF2 (alternative splicing factor/splicing factor 2) and SRPK (serine arginine domain protein kinase), and inhibitors of these molecules can inhibit angiogenesis in the eye, and splice site selection in cancer cells, opening up the possibility of using splicing factor inhibitors as novel anti-angiogenic therapeutics. Endogenous anti-angiogenic VEGF(xxx)b isoforms are cytoprotective for endothelial, epithelial and neuronal cells in vitro and in vivo, suggesting both an improved safety profile and an explanation for unpredicted anti-VEGF side effects. In summary, C-terminal distal splicing is a key component of VEGF biology, overlooked by the vast majority of publications in the field, and these findings require a radical revision of our understanding of VEGF biology in normal human physiology.
C1 [Qiu, Yan; Hoareau-Aveilla, Coralie; Oltean, Sebastian; Harper, Steven J.; Bates, David O.] Univ Bristol, Microvasc Res Labs, Bristol Heart Inst, Dept Physiol & Pharmacol,Sch Vet Sci, Bristol BS2 8EJ, Avon, England.
C3 University of Bristol
RP Bates, DO (通讯作者)，Univ Bristol, Microvasc Res Labs, Bristol Heart Inst, Dept Physiol & Pharmacol,Sch Vet Sci, Southwell St, Bristol BS2 8EJ, Avon, England.
EM Dave.Bates@bristol.ac.uk
RI Hoareau-Aveilla, Coralie/G-3787-2017
OI Hoareau-Aveilla, Coralie/0000-0001-5506-4552; Oltean,
   Sebastian/0000-0001-7890-8439; Bates, David/0000-0003-4850-2360
FU British Heart Foundation [PG08/022/21636, FS/05/114/19959, FS/40/09,
   BS/06/005, FS/07/059/24011]; Cancer Research UK [C11392/A10484];
   Wellcome Trust [69134, 69029, 79633]; Association for International
   Cancer Research; Skin Cancer Research Fund; Medical Research Council
   [GR0600920]; Richard Bright VEGF Research Trust; Medical Research
   Council [G0600920] Funding Source: researchfish; MRC [G0600920] Funding
   Source: UKRI
FX This work was supported by the British Heart Foundation [grant numbers
   PG08/022/21636, FS/05/114/19959, FS/40/09, BS/06/005 and
   FS/07/059/24011], Cancer Research UK [grant number C11392/A10484], the
   Wellcome Trust [grant numbers 69134, 69029 and 79633], the Association
   for International Cancer Research, Skin Cancer Research Fund, the
   Medical Research Council [grant number GR0600920] and the Richard Bright
   VEGF Research Trust.
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NR 62
TC 82
Z9 88
U1 0
U2 10
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0300-5127
EI 1470-8752
J9 BIOCHEM SOC T
JI Biochem. Soc. Trans.
PD DEC
PY 2009
VL 37
BP 1207
EP 1213
DI 10.1042/BST0371207
PN 6
PG 7
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 531EK
UT WOS:000272646000011
PM 19909248
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Vargas, A
   Eid, M
   Fanchaouy, M
   Gurny, R
   Delie, F
AF Vargas, Angelica
   Eid, Michael
   Fanchaouy, Mohammed
   Gurny, Robert
   Delie, Florence
TI In vivo photodynamic activity of photosensitizer-loaded nanoparticles:
   Formulation properties, administration parameters and biological issues
   involved in PDT outcome
SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
LA English
DT Article
DE photodynamic therapy; polymeric nanoparticles; nanoparticle size; chick
   chorioallantoic membrane (CAM) model; photosensitizer; in vivo; vascular
   occlusion; endothelial cells; age-related macular degeneration; cancer
ID EMULSIFICATION-DIFFUSION; SALTING-OUT; BIODISTRIBUTION; EXTRAVASATION;
   THERAPY; VITRO
AB Encapsulation of hydrophobic photosensitizers (PS) into polymeric nanoparticles (NP) has proven to be an effective alternative to organic solvents for their formulation. As NP size controls NP passage through endothelial barriers, it is a key parameter for achieving passive targeting of cancer tissues and choroidal neovascularization, secondary to age-related macular degeneration, the main applications of photodynamic therapy. In the present study, a hydrophobic PS, the meso-tetra(p-hydroxyphenyl)porphyrin, was encapsulated into biodegradable NP made of poly(D,L-lactide-co-glycolide) 50:50 via an emulsification-diffusion technique. NP batches having mean diameters of 117, 285, and 593 nm were obtained with narrow size distribution. Using the chorioallantoic membrane (CAM) of the developing chick embryo, it was demonstrated that the increase in the NP size decreased photodynamic activity in vivo. The activity of PS-loaded NP was not influenced by the volume of injection and was kept intact at least 6 It after NP reconstitution. Investigation of NP circulation after IV administration by fluorescence measurements revealed that 117 nm NP reached T-max earlier than larger NP. Confocal imaging of CAM vessels demonstrated PS uptake by endothelial cells after NP administration. It was concluded that NP size controls the photodynamic activity of the encapsulated PS. (C) 2007 Elsevier B.V. All rights reserved.
C1 [Vargas, Angelica; Gurny, Robert; Delie, Florence] Univ Lausanne, Univ Geneva, Sch Pharmaceut Sci, Dept Pharmaceut & Biopharmaceut, CH-1211 Geneva 4, Switzerland.
   [Eid, Michael] Free Univ Berlin, Dept Educ Sci & Psychol, D-1000 Berlin, Germany.
   [Fanchaouy, Mohammed] Univ Geneva, Dept Zool & Anim Biol, CH-1211 Geneva 4, Switzerland.
C3 University of Geneva; University of Lausanne; Free University of Berlin;
   University of Geneva
RP Delie, F (通讯作者)，Univ Lausanne, Univ Geneva, Sch Pharmaceut Sci, Dept Pharmaceut & Biopharmaceut, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland.
EM Florence.delie@pharm.unige.ch
RI Delie, Florence/H-1526-2015
OI Delie, Florence/0000-0002-2637-5949
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NR 29
TC 41
Z9 45
U1 0
U2 26
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0939-6411
EI 1873-3441
J9 EUR J PHARM BIOPHARM
JI Eur. J. Pharm. Biopharm.
PD MAY
PY 2008
VL 69
IS 1
BP 43
EP 53
DI 10.1016/j.ejpb.2007.09.021
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 300WE
UT WOS:000255855100005
PM 18023564
DA 2022-11-30
ER

PT J
AU Kleinman, ME
   Yamada, K
   Takeda, A
   Chandrasekaran, V
   Nozaki, M
   Baffi, JZ
   Albuquerque, RJC
   Yamasaki, S
   Itaya, M
   Pan, YZ
   Appukuttan, B
   Gibbs, D
   Yang, ZL
   Kariko, K
   Ambati, BK
   Wilgus, TA
   DiPietro, LA
   Sakurai, E
   Zhang, K
   Smith, JR
   Taylor, EW
   Ambati, J
AF Kleinman, Mark E.
   Yamada, Kiyoshi
   Takeda, Atsunobu
   Chandrasekaran, Vasu
   Nozaki, Miho
   Baffi, Judit Z.
   Albuquerque, Romulo J. C.
   Yamasaki, Satoshi
   Itaya, Masahiro
   Pan, Yuzhen
   Appukuttan, Binoy
   Gibbs, Daniel
   Yang, Zhenglin
   Kariko, Katalin
   Ambati, Balamurali K.
   Wilgus, Traci A.
   DiPietro, Luisa A.
   Sakurai, Eiji
   Zhang, Kang
   Smith, Justine R.
   Taylor, Ethan W.
   Ambati, Jayakrishna
TI Sequence- and target-independent angiogenesis suppression by siRNA via
   TLR3
SO NATURE
LA English
DT Article
ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; SMALL INTERFERING RNAS;
   IN-VIVO DELIVERY; NF-KAPPA-B; CHOROIDAL NEOVASCULARIZATION; OCULAR
   NEOVASCULARIZATION; NEGATIVE REGULATOR; ENDOTHELIAL-CELLS; SIGNALING
   PATHWAY
AB Clinical trials of small interfering RNA ( siRNA) targeting vascular endothelial growth factor-A ( VEGFA) or its receptor VEGFR1 ( also called FLT1), in patients with blinding choroidal neovascularization ( CNV) from age- related macular degeneration, are premised on gene silencing by means of intracellular RNA interference ( RNAi). Weshow instead that CNV inhibition is a siRNA- class effect: 21- nucleotide or longer siRNAs targeting non- mammalian genes, non- expressed genes, non- genomic sequences, pro- and anti- angiogenic genes, and RNAi- incompetent siRNAs all suppressed CNV in mice comparably to siRNAs targeting Vegfa or Vegfr1 without off- target RNAi or interferon-alpha/beta activation. Non- targeted ( against non- mammalian genes) and targeted ( against Vegfa or Vegfr1) siRNA suppressed CNV via cell- surface toll- like receptor 3 ( TLR3), its adaptor TRIF, and induction of interferon-gamma and interleukin- 12. Non- targeted siRNA suppressed dermal neovascularization in mice as effectively as Vegfa siRNA. siRNA- induced inhibition of neovascularization required a minimum length of 21 nucleotides, a bridging necessity in a modelled 2: 1 TLR3 - RNA complex. Choroidal endothelial cells from people expressing the TLR3 coding variant 412FF were refractory to extracellular siRNA- induced cytotoxicity, facilitating individualized pharmacogenetic therapy. Multiple human endothelial cell types expressed surface TLR3, indicating that generic siRNAs might treat angiogenic disorders that affect 8% of the world's population, and that siRNAs might induce unanticipated vascular or immune effects.
C1 [Kleinman, Mark E.; Yamada, Kiyoshi; Takeda, Atsunobu; Nozaki, Miho; Baffi, Judit Z.; Albuquerque, Romulo J. C.; Ambati, Jayakrishna] Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.
   [Albuquerque, Romulo J. C.; Ambati, Jayakrishna] Univ Kentucky, Dept Physiol, Lexington, KY 40506 USA.
   [Chandrasekaran, Vasu] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
   [Yamasaki, Satoshi; Itaya, Masahiro; Sakurai, Eiji] Nagoya City Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 4678601, Japan.
   [Pan, Yuzhen; Appukuttan, Binoy; Smith, Justine R.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA.
   [Gibbs, Daniel; Yang, Zhenglin; Ambati, Balamurali K.; Zhang, Kang] Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT 84132 USA.
   [Gibbs, Daniel; Yang, Zhenglin; Zhang, Kang] Univ Utah, Sch Med, Program Human Mol Biol & Genet, Eccles Inst Human Genet, Salt Lake City, UT 84132 USA.
   [Kariko, Katalin] Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA.
   [Ambati, Balamurali K.] Vet Affairs Salt Lake City Healthcare Syst, Salt Lake City, UT 84148 USA.
   [Wilgus, Traci A.; DiPietro, Luisa A.] Univ Illinois, Coll Dent, Ctr Wound Healing & Tissue Regenerat, Chicago, IL 60612 USA.
   [Taylor, Ethan W.] Univ N Carolina, Mol Med Lab, Greensboro, NC 27402 USA.
C3 University of Kentucky; University of Kentucky; University of North
   Carolina; University of North Carolina Chapel Hill; Nagoya City
   University; Oregon Health & Science University; Utah System of Higher
   Education; University of Utah; Utah System of Higher Education;
   University of Utah; University of Pennsylvania; US Department of
   Veterans Affairs; University of Illinois System; University of Illinois
   Chicago; University of Illinois Chicago Hospital; University of North
   Carolina; University of North Carolina Greensboro
RP Ambati, J (通讯作者)，Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.
EM jamba2@email.uky.edu
RI Smith, Justine/Y-9044-2019; Zhang, Kang/Y-2740-2019; Peng,
   Chunwei/F-6788-2010
OI Smith, Justine/0000-0002-4756-5493; Zhang, Kang/0000-0002-4549-1697;
   Kleinman, Mark/0000-0001-8557-7949
FU NATIONAL EYE INSTITUTE [R01EY018350, R01EY018836, R01EY015422] Funding
   Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
   [R01GM050875] Funding Source: NIH RePORTER; NEI NIH HHS [R01
   EY018350-02, R01 EY018836, R01 EY018350, R01 EY018836-01, R01
   EY015422-04, R01 EY015422] Funding Source: Medline; NIGMS NIH HHS [R01
   GM050875] Funding Source: Medline
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NR 55
TC 721
Z9 788
U1 5
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 3
PY 2008
VL 452
IS 7187
BP 591
EP U1
DI 10.1038/nature06765
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 282KR
UT WOS:000254567200037
PM 18368052
OA Green Accepted, Bronze, Green Submitted
DA 2022-11-30
ER

PT J
AU Hornan, DM
   Peirson, SN
   Hardcastle, AJ
   Molday, RS
   Cheetham, ME
   Webster, AR
AF Hornan, Daniel M.
   Peirson, Stuart N.
   Hardcastle, Alison J.
   Molday, Robert S.
   Cheetham, Michael E.
   Webster, Andrew R.
TI Novel retinal and cone photoreceptor transcripts revealed by human
   macular expression profiling
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; FACTOR-H POLYMORPHISM; HOMEOBOX GENE CRX;
   BEAVER DAM EYE; HISTONE DEACETYLASE; MICROARRAY ANALYSIS; DEGENERATION;
   SUSCEPTIBILITY; LOCUS; INCREASES
AB PURPOSE. The macula is essential for visual acuity. It contains many more cone photoreceptors than does the peripheral retina. In this study, macular gene expression was compared with that in the rod-rich peripheral retina.
   METHODS. Two-millimeter foveomacular and four-millimeter macular punches from human donor eyes, in addition to sections of midperipheral retina, were used to study differential gene expression. Multiple microarray experiments were combined with quantitative PCR and bioinformatic analyses. In the present study, the expression of both known and previously unidentified retinal genes was determined.
   RESULTS. Several macula enriched transcripts were revealed. Nuclear pore complex interacting protein (NPIP) and eukaryotic translation initiation factor 2 alpha kinase (GCN2) were expressed at levels approaching that of red/green cone opsin in the macula. The protein products of several genes highlighted using these expression analyses were also localized in the retina. Both NPIP and histone deacetylase 9 (HDAC9) proteins were detected in cone photoreceptor outer segments.
   CONCLUSIONS. Characterizing macula enriched transcripts is an important stepping-stone in understanding the molecular basis for visual acuity in the retina. The approach also provides excellent candidates for diseases that affect the macula and fovea such as age-related macular degeneration (AMD). Indeed, several of these transcripts, such as NPIP and GCN2, have genomic loci that are consistent with being candidate genes for AMD.
C1 UCL, Inst Ophthalmol, London, England.
   Imperial Coll London, Dept Visual Neurosci, London, England.
   Univ British Columbia, Macular Res Ctr, Vancouver, BC, Canada.
C3 University of London; University College London; Imperial College
   London; University of British Columbia
RP Hornan, DM (通讯作者)，Inst Ophthalmol, 11-43 Bath St, London EC1 9EL, England.
EM d.hornan@doctors.org.uk
RI Cheetham, Michael/B-4672-2011
OI Cheetham, Michael/0000-0001-6429-654X; Hardcastle,
   Alison/0000-0002-0038-6770
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NR 37
TC 24
Z9 24
U1 0
U2 3
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 2007
VL 48
IS 12
BP 5388
EP 5396
DI 10.1167/iovs.07-0355
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 238MB
UT WOS:000251450800008
PM 18055785
DA 2022-11-30
ER

PT J
AU Tatar, O
   Shinoda, K
   Adam, A
   Eckert, T
   Eckardt, C
   Lucke, K
   Deuter, C
   Bartz-Schmidt, KU
   Grisanti, S
AF Tatar, Olcay
   Shinoda, Kei
   Adam, Annemarie
   Eckert, Tillmann
   Eckardt, Claus
   Lucke, Klaus
   Deuter, Christoph
   Bartz-Schmidt, Karl Ulrich
   Grisanti, Salvatore
TI Effect of verteporfin photodynamic therapy on endostatin and
   angiogenesis in human choroidal neovascular membranes
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GROWTH-FACTOR VEGF; LIMITED MACULAR TRANSLOCATION; HYPOXIC INDUCTION;
   FACTOR EXPRESSION; IN-VITRO; DEGENERATION; ANGIOSTATIN; CELLS;
   INHIBITION; MECHANISMS
AB Aim: To evaluate the effect of verteporfin photodynamic therapy ( PDT) on endostatin with regard to expression of vascular endothelial growth factor ( VEGF) in human choroidal neovascular membranes ( CNVs) secondary to age- related macular degeneration.
   Methods: A retrospective review of an interventional case series of 68 patients who underwent removal of CNV. 29 patients were treated with PDT 3-655 days before surgery. 39 CNVs without previous treatment were used as controls. CNVs were stained for CD34, CD105, Ki-67, cytokeratin 18, endostatin, E-selectin and VEGF. "Predominance score of VEGF over endostatin'' ( mean) was defined as the difference between VEGF and endostatin staining scores.
   Results: In four CNVs treated by PDT 3 days previously, PS was significantly higher in the retinal pigment epithelium ( mean = 2.5, p = 0.006) and stroma ( mean = 2, p = 0.015) than in the control group ( mean = 0). At longer post-PDT intervals, PS was significantly decreased in the retinal pigment epithelium ( mean = 0, p = 0.019) and stroma ( mean = 0, p = 0.015). Proliferative activity was high ( p = 0.023), but mostly related to inflammatory cells. PDT did not influence E-selectin expression significantly.
   Conclusions: VEGF predominance over endostatin early after PDT might contribute to enhanced angiogenic activity associated with recurrences. Strategies upregulating or replacing endostatin early after PDT might increase the effectiveness of PDT.
C1 Univ Tubingen, Univ Eye Hosp, Ctr Ophthalmol, D-72076 Tubingen, Germany.
   Natl Inst Sensory Organs, Lab Visual Physiol, Tokyo, Japan.
   Univ Tubingen, Dept Pathol, Tubingen, Germany.
   Augenklin, Staedt Kliniken, Frankfurt, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Eberhard Karls University of Tubingen; Eberhard Karls
   University Hospital; University of Hamburg; University Medical Center
   Hamburg-Eppendorf
RP Grisanti, S (通讯作者)，Univ Tubingen, Univ Eye Hosp, Ctr Ophthalmol, Schleichstr 12-15, D-72076 Tubingen, Germany.
EM grisanti@med.uni-tuebingen.de
RI Shinoda, Kei/ABC-7993-2020
OI Shinoda, Kei/0000-0002-1543-9345
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NR 60
TC 31
Z9 33
U1 0
U2 1
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 FEB
PY 2007
VL 91
IS 2
BP 166
EP 173
DI 10.1136/bjo.2006.105288
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 128UL
UT WOS:000243684200016
PM 16987895
OA Green Published
DA 2022-11-30
ER

PT J
AU Nirmalan, PK
   Katz, J
   Robin, AL
   Ticlsch, JM
   Namperumalsamy, P
   Kim, R
   Narendran, V
   Ramakrishnan, R
   Krishnadas, R
   Thulasiraj, RD
   Suan, E
AF Nirmalan, PK
   Katz, J
   Robin, AL
   Ticlsch, JM
   Namperumalsamy, P
   Kim, R
   Narendran, V
   Ramakrishnan, R
   Krishnadas, R
   Thulasiraj, RD
   Suan, E
TI Prevalence of vitreoretinal disorders in a rural population of southern
   India - The Aravind Comprehensive Eye Study
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; SENILE MACULAR DEGENERATION;
   BLUE-MOUNTAINS-EYE; RISK-FACTORS; DIABETIC-RETINOPATHY;
   URBAN-POPULATION; IMPAIRMENT; BLINDNESS; FEATURES
AB Objective: To determine the magnitude of vitreoretinal disorders in a rural southern Indian population.
   Methods: Cluster sampling was used to identify individuals 40 years and older in Tamil Nadu in southern India. Demographic details, vision measurement and refraction using logMAR charts, anterior segment slitlamp examination, dilated posterior segment slitlamp examination using a 78-diopter (D) lens, and indirect ophthalmoscopy using a 20-D lens were performed.
   Results: Complete retinal data were available for 4917 (95.5%) of the 5150 persons examined. The prevalence of any vitreoretinal disorder was 10.4% (95% confidence interval [ CI], 9.5%-11.3%). The population prevalence of bilateral blindness among persons with vitreoretinal disorders was 0.3% (95% CI, 0.2%-0.5%). The prevalence of diabetic retinopathy was 0.5% (95% CI, 0.3%-0.7%) in the general population and 10.5% (95% CI, 6.5%-14.5%) in patients with diabetes mellitus. Only 6.7% of individuals with diabetic retinopathy had previous ophthalmic examinations. The prevalences of early and late age-related macular degeneration were 2.7% (95% CI, 2.2%-3.2%) and 0.6% (95% CI, 0.4%-0.8%), respectively.
   Conclusions: Vitreoretinal diseases appear to be a major public health problem in India. Emphasis on diabetic screening, diabetic therapy, and appropriate laser therapy of diabetic retinopathy must be explored.
C1 Aravind Med Res Fdn, Aravind Eye Care Syst, 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 Publ Hlth, Dana Ctr Prevent Ophthalmol, Baltimore, MD USA.
   Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
   Univ Maryland, Sch Med, Dept Ophthalmol, Baltimore, MD 21201 USA.
C3 Johns Hopkins University; Johns Hopkins Bloomberg School of Public
   Health; Johns Hopkins University; Johns Hopkins University; Johns
   Hopkins University; University System of Maryland; University of
   Maryland Baltimore
RP Robin, AL (通讯作者)，Lake Falls Profess Bldg,6115 Falls Rd,Suite 333, Baltimore, MD 21209 USA.
EM glaucomacxpert@cs.com
OI Nirmalan, Praveen/0000-0003-0655-8104; Tielsch,
   James/0000-0002-1151-060X; Robin, Alan/0000-0003-1959-8770; Katz,
   Joanne/0000-0002-5997-7823
CR [Anonymous], 1985, WHO TECH REP SER, P1
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NR 35
TC 96
Z9 98
U1 0
U2 1
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 APR
PY 2004
VL 122
IS 4
BP 581
EP 586
DI 10.1001/archopht.122.4.581
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 812GT
UT WOS:000220828700018
PM 15078677
DA 2022-11-30
ER

PT J
AU Meng, N
   Xie, HX
   Hou, JR
   Chen, YB
   Wu, MJ
   Guo, YW
   Jiang, CS
AF Meng Ning
   Xie Hong-Xu
   Hou Jia-Rong
   Chen Yon-Bin
   Wu Meng-Jun
   Guo Yue-Wei
   Jiang Cheng-Shi
TI Design and semisynthesis of oleanolic acid derivatives as VEGF in-
   hibitors: Inhibition of VEGF-induced proliferation, angiogenesis, and
   VEGFR2 activation in HUVECs
SO CHINESE JOURNAL OF NATURAL MEDICINES
LA English
DT Article
DE Oleanolic acid; Structural modification; VEGF inhibitor; VEGFR2;
   Angiogenesis
ID ENDOTHELIAL GROWTH-FACTOR; CANCER
AB Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases, such as cancer, rheumatoid arthritis, and age-related macular degeneration. Recent studies have revealed that oleanolic acid (OA), a natural pentacyclic triterpenoid, inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs, which may represent an attractive VEGF inhibitor. In this paper, rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential. As a result, a series of novel OA derivatives, possessing alpha,beta-unsat-urated ketone system in ring A and amide functional group at C-28, were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs. The results showed that two promising derivatives, OA-1 and OA-16, exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs, compared with OA. The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VEGFR2 activation. Furthermore, small interfering RNA experiments were performed to confirm that both compounds inhibited VEGFinduced angiogenesis via VEGFR2. Thus, the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors, which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.
C1 [Meng Ning; Xie Hong-Xu; Hou Jia-Rong; Chen Yon-Bin; Jiang Cheng-Shi] Univ Jinan, Sch Biol Sci & Technol, Jinan 250022, Peoples R China.
   [Wu Meng-Jun; Guo Yue-Wei] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China.
C3 University of Jinan; Chinese Academy of Sciences; Shanghai Institute of
   Materia Medica, CAS
RP Meng, N; Jiang, CS (通讯作者)，Univ Jinan, Sch Biol Sci & Technol, Jinan 250022, Peoples R China.; Guo, YW (通讯作者)，Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China.
EM mls_mengn@ujn.edu.cn; ywguo@simm.ac.cn; bio_jiangcs@ujn.edu.cn
FU National Natural Science Foundation of China [21672082, 31671214];
   Natural Science Foundation of Shandong Province [ZR2019YQ31, ZR2020YQ52,
   ZR2020MB103]; Project of Shandong Province Higher Educational Youth
   Innovation Science and Technology Program [2020KJE006]; Science and
   Technology Project of University of Jinan [XKY2004]
FX This work was supported by the National Natural Science Foundation of
   China (Nos. 21672082 and 31671214), the Natural Science Foundation of
   Shandong Province (Nos. ZR2019YQ31, ZR2020YQ52, and ZR2020MB103), the
   Project of Shandong Province Higher Educational Youth Innovation Science
   and Technology Program (No. 2020KJE006), and the Science and Technology
   Project of University of Jinan (No. XKY2004).
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NR 33
TC 0
Z9 0
U1 3
U2 4
PU CHINESE JOURNAL NATURAL MEDICINES
PI NANJING
PA 24, TONGJIA XIANG, NANJING, 210009, PEOPLES R CHINA
SN 2095-6975
EI 1875-5364
J9 CHIN J NAT MEDICINES
JI Chin. J. Nat. Med.
PD MAR
PY 2022
VL 20
IS 3
BP 229
EP 240
DI 10.1016/S1875-5364(22)60159-6
PG 12
WC Integrative & Complementary Medicine; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Integrative & Complementary Medicine; Pharmacology & Pharmacy
GA 0O9HA
UT WOS:000783832900009
PM 35369968
DA 2022-11-30
ER

PT J
AU Acker, N
   Smith, H
   Devine, C
   Oltjen, SL
   Tsiropoulou, S
   Smit-McBride, Z
   Lange, K
   Blacque, OE
   Matsubara, JA
   Gordus, A
   Golden, A
   Vogel, BE
AF Acker, Natalie
   Smith, Harold
   Devine, Claire
   Oltjen, Sharon L.
   Tsiropoulou, Sofia
   Smit-McBride, Zeljka
   Lange, Karen
   Blacque, Oliver E.
   Matsubara, Joanne A.
   Gordus, Andrew
   Golden, Andy
   Vogel, Bruce E.
TI A complement factor H homolog, heparan sulfation and syndecan maintain
   inversin compartment boundaries in C. elegans cilia
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE complement factor H; heparan sulfate; syndecan; cilia; inversin
ID MACULAR DEGENERATION; GENE-EXPRESSION; PROTEIN; CELL; LOCALIZATION;
   POLYMORPHISM; PATHWAY; TRAFFICKING; MECHANISMS; MUTATIONS
AB Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. Canonical disease models suggest that defective interactions between complement factor H (CFH) and cell surface heparan sulfate (HS) result in increased alternative complement pathway activity, cytolytic damage, and tissue inflammation in the retina. Although these factors are thought to contribute to increased disease risk, multiple studies indicate that noncanonical mechanisms that result from defective CFH and HS interaction may contribute to the progression of AMD as well. A total of 60 ciliated sensory neurons in the nematode Caenorhabditis elegans detect chemical, olfactory, mechanical, and thermal cues in the environment. Here, we find that a C. elegans CFH homolog localizes on CEP mechanosensory neuron cilia where it has noncanonical roles in maintaining inversin/NPHP-2 within its namesake proximal compartment and preventing inversin/NPHP2 accumulation in distal cilia compartments in aging adults. CFH localization and maintenance of inversin/NPHP-2 compartment integrity depend on the HS 3-O sulfotransferase HST-3.1 and the transmembrane proteoglycan syndecan/SDN-1. Defective inversin/NPHP-2 localization in mouse and human photoreceptors with CFH mutations indicates that these functions and interactions may be conserved in vertebrate sensory neurons, suggesting that previously unappreciated defects in cilia structure may contribute to the progressive photoreceptor dysfunction associated with CFH loss-of-function mutations in some AMD patients.
C1 [Acker, Natalie; Devine, Claire; Vogel, Bruce E.] Univ Maryland, Univ Maryland Sch Med, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA.
   [Smith, Harold; Golden, Andy] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
   [Oltjen, Sharon L.; Smit-McBride, Zeljka] Univ Calif Davis, Vitreoretinal Res Lab, Dept Ophthalmol & Vis Sci, Davis, CA 95616 USA.
   [Tsiropoulou, Sofia; Lange, Karen; Blacque, Oliver E.] Univ Coll Dublin, UCD Conway Inst, Sch Biomol & Biomed Res, Dublin 4, Ireland.
   [Matsubara, Joanne A.] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 3N9, Canada.
   [Gordus, Andrew] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21211 USA.
   [Vogel, Bruce E.] Univ Maryland, Univ Maryland Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
C3 University System of Maryland; University of Maryland Baltimore;
   National Institutes of Health (NIH) - USA; NIH National Institute of
   Diabetes & Digestive & Kidney Diseases (NIDDK); University of California
   System; University of California Davis; University College Dublin;
   University of British Columbia; Johns Hopkins University; University
   System of Maryland; University of Maryland Baltimore
RP Vogel, BE (通讯作者)，Univ Maryland, Univ Maryland Sch Med, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA.; Vogel, BE (通讯作者)，Univ Maryland, Univ Maryland Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
EM bvogel@som.umaryland.edu
OI Oltjen, Sharon/0000-0002-6698-4810; Matsubara, Joanne
   A./0000-0002-3689-3117; Lange, Karen I./0000-0002-2414-5277; Blacque,
   Oliver/0000-0003-1598-2695; , Sofia/0000-0002-3760-9317; Gordus,
   Andrew/0000-0002-5550-0286
FU NIH [R21EY030188]; Canadian Institutes of Health Research; NIH, National
   Institute of Diabetes and Digestive and Kidney Diseases; NIH Office of
   Research Infrastructure Programs [P40 OD010440]
FX We thank Maria Doitsidou, Hannes Bulow, Inna Nechipurenko, Piali
   Sengupta, Maureen Barr, Victor Jensen, Michel Leroux, and Mervyn
   Monteiro for their exceptional generosity in sharing C. elegans strains
   and constructs and Dominique Rasoloson, Alexander Paix, Geraldine
   Seydoux, Amy Fabritius, and Tyler Hansen for CRISPR-Cas9 reagents and
   assistance. In addition, we thank Roxana Radu for providing tissue from
   cfh<SUP>-/-</SUP>mice obtained originally from Matthew Pickering and
   Gregory Hageman. We also thank Andy Ziman for assistance with
   microscopy, Murray Pressman, Shengyun Fang, and Jon Lederer for helpful
   discussions, and Zubair Ahmed and Saumil Sethna for comments on the
   manuscript. B.E.V. is supported by funding from NIH Grant R21EY030188.
   J.A.M. is supported by the Canadian Institutes of Health Research. H.S.
   and A. Golden are supported by the Intramural Research Program of the
   NIH, National Institute of Diabetes and Digestive and Kidney Diseases.
   Some C. elegans strains were provided by the CGC, which is funded by NIH
   Office of Research Infrastructure Programs (P40 OD010440), and the C.
   elegans Reverse Genetics Core Facility at the University of British
   Columbia, which is part of the international C. elegans Gene Knockout
   Consortium.
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NR 69
TC 1
Z9 1
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 20
PY 2021
VL 118
IS 16
AR e2016698118
DI 10.1073/pnas.2016698118
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA RQ5ML
UT WOS:000642462800005
PM 33859044
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Kim, MH
   Kim, DH
   Yang, SG
   Kim, DY
AF Kim, Myung Hee
   Kim, Do-Hun
   Yang, Su Geun
   Kim, Dae Yu
TI Improved effect of a mitochondria-targeted antioxidant on hydrogen
   peroxide-induced oxidative stress in human retinal pigment epithelium
   cells
SO BMC PHARMACOLOGY & TOXICOLOGY
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium;
   Mitochondrial function; Antioxidants
AB Background: Oxidative damage to retinal pigment epithelial (RPE) cells contributes to the development of age-related macular degeneration, which is among the leading causes of visual loss in elderly people. In the present study, we evaluated the protective role of triphenylphosphonium (TPP)-Niacin against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells.
   Methods: The cellular viability, lactate dehydrogenase release, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were determined under treatment with H2O2 or pre-treatment with TPP-Niacin. The expression level of mitochondrial related genes and some transcription factors were assessed using real-time polymerase chain reaction (RT-qPCR).
   Results: TPP-Niacin significantly improved cell viability, reduced ROS generation, and increased the antioxidant enzymes in H2O2-treated ARPE-19 cells. Mitochondrial dysfunction from the H2O2-induced oxidative stress was also considerably diminished by TPP-Niacin treatment, along with reduction of the mitochondrial membrane potential (MMP) and upregulation of the mitochondrial-associated gene. In addition, TPP-Niacin markedly enhanced the expression of transcription factors (PGC-1 alpha and NRF2) and antioxidant-associated genes (especially HO-1 and NQO-1).
   Conclusion: We verified the protective effect of TPP-Niacin against H2O2-induced oxidative stress in RPE cells. TPP-Niacin is believed to protect against mitochondrial dysfunction by upregulating antioxidant-related genes, such as PGC-1 alpha, NRF2, HO-1, and NQO-1, in RPE cells.
C1 [Kim, Myung Hee; Kim, Do-Hun; Yang, Su Geun; Kim, Dae Yu] Inha Univ, Inha Res Inst Aerosp Med, Incheon 22212, South Korea.
   [Kim, Do-Hun; Yang, Su Geun] Inha Univ, Dept Biomed Sci, BK21 FOUR Program Biomed Sci & Engn, Coll Med, Incheon 22332, South Korea.
   [Kim, Dae Yu] Inha Univ, Coll Engn, Dept Elect Engn, Incheon 22212, South Korea.
   [Kim, Dae Yu] Inha Univ, Ctr Sensor Syst, Incheon 22212, South Korea.
C3 Inha University; Inha University; Inha University; Inha University
RP Yang, SG; Kim, DY (通讯作者)，Inha Univ, Inha Res Inst Aerosp Med, Incheon 22212, South Korea.; Yang, SG (通讯作者)，Inha Univ, Dept Biomed Sci, BK21 FOUR Program Biomed Sci & Engn, Coll Med, Incheon 22332, South Korea.; Kim, DY (通讯作者)，Inha Univ, Coll Engn, Dept Elect Engn, Incheon 22212, South Korea.; Kim, DY (通讯作者)，Inha Univ, Ctr Sensor Syst, Incheon 22212, South Korea.
EM sugeun.yang@inha.ac.kr; dyukim@inha.ac.kr
FU Ministry of Education National Research Foundation (NRF) through the
   Basic Science Research Program [NRF-2017R1D1A1B03030396,
   2018R1A6A1A03025523]; Bio & Medical Technology Development Program of
   the National Research Foundation (NRF); Ministry of Science ICT
   [2019M3E5D1A02069623]
FX The work was supported by the Ministry of Education National Research
   Foundation (NRF) through the Basic Science Research Program under Grant
   NRF-2017R1D1A1B03030396 and 2018R1A6A1A03025523 and was partially
   supported by the Bio & Medical Technology Development Program of the
   National Research Foundation (NRF) & funded by the Ministry of Science &
   ICT (2019M3E5D1A02069623).
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NR 52
TC 5
Z9 6
U1 3
U2 23
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 2050-6511
J9 BMC PHARMACOL TOXICO
JI BMC Pharmacol. Toxicol.
PD JAN 20
PY 2021
VL 22
IS 1
AR 7
DI 10.1186/s40360-020-00471-w
PG 13
WC Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Toxicology
GA PU3BF
UT WOS:000609178500001
PM 33472699
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Hu, LM
   Guo, J
   Zhou, L
   Zhu, S
   Wang, CM
   Liu, JW
   Hu, SS
   Yang, ML
   Lin, CJ
AF Hu, Liming
   Guo, Jia
   Zhou, Li
   Zhu, Sen
   Wang, Chunming
   Liu, Jiawei
   Hu, Shanshan
   Yang, Mulin
   Lin, Changjun
TI Hydrogen Sulfide Protects Retinal Pigment Epithelial Cells from
   Oxidative Stress-Induced Apoptosis and Affects Autophagy
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID DEATH; RPE; INFLAMMATION; H2S; DEGENERATION; ACTIVATION; MECHANISM;
   DAMAGE; BRAIN; MTOR
AB Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness among the elderly. AMD is characterized by retinal pigment epithelial (RPE) cell dysfunction. However, the pathogenesis of AMD is still unclear, and there is currently no effective treatment. Accumulated evidence indicates that oxidative stress and autophagy play a crucial role in the development of AMD. H2S is an antioxidant that can directly remove intracellular superoxide anions and hydrogen peroxide. The purpose of this study is to investigate the antioxidative effect of H2S in RPE cells and its role in autophagy. The results show that exogenous H2S (NaHS) pretreatment effectively reduces H2O2-induced oxidative stress, oxidative damage, apoptosis, and inflammation in ARPE-19 cells. NaHS pretreatment also decreased autophagy levels raised by H2O2, increased cell viability, and ameliorated cell morphological damage. Interestingly, the suppression of autophagy by its inhibitor 3-MA showed an increase of cell viability, amelioration of morphology, and a decrease of apoptosis. In summary, oxidative stress causes ARPE-19 cell injury by inducing cell autophagy. However exogenous H2S is shown to attenuate ARPE-19 cell injury, decrease apoptosis, and reduce the occurrence of autophagy-mediated by oxidative stress. These findings suggest that autophagy might play a crucial role in the development of AMD, and exogenous H2S has a potential value in the treatment of AMD.
C1 [Hu, Liming; Guo, Jia; Zhou, Li; Zhu, Sen; Wang, Chunming; Liu, Jiawei; Hu, Shanshan; Yang, Mulin; Lin, Changjun] Lanzhou Univ, Sch Life Sci, Lanzhou, Peoples R China.
C3 Lanzhou University
RP Lin, CJ (通讯作者)，Lanzhou Univ, Sch Life Sci, Lanzhou, Peoples R China.
EM linc@lzu.edu.cn
RI Hu, Liming/GSM-8276-2022; Wang, Chunming/A-4830-2009
OI Wang, Chunming/0000-0002-2810-9820; Lin, Changjun/0000-0002-9134-548X;
   sen, zhu/0000-0002-0552-8985
FU LZU-Senmiao Cooperation
FX The authors are thankful to the Core Facility of School of Life
   Sciences, Lanzhou University. This work is supported partly by the
   LZU-Senmiao Cooperation.
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NR 63
TC 5
Z9 5
U1 1
U2 7
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 DEC 31
PY 2020
VL 2020
AR 8868564
DI 10.1155/2020/8868564
PG 15
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA PU7PV
UT WOS:000609494100008
PM 33488939
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zhang, XL
   Zhu, MH
   Xie, LQ
   Sun, XD
   Xu, JW
   Guo, Y
   Liu, D
   Shi, YW
   Xu, X
   Song, E
AF Zhang, Xiaoli
   Zhu, Manhui
   Xie, Laiqing
   Sun, Xiaodong
   Xu, Jiaowen
   Guo, Yang
   Liu, Dong
   Shi, Yunwei
   Xu, Xun
   Song, E.
TI Cabozantinib, a Multityrosine Kinase Inhibitor of MET and VEGF Receptors
   Which Suppresses Mouse Laser-Induced Choroidal Neovascularization
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; C-MET; OCULAR NEOVASCULARIZATION;
   ANGIOGENESIS; PROLIFERATION; METASTASIS; XL184; MODEL; RESISTANCE; CELLS
AB Choroidal neovascularization (CNV) is a leading cause of blindness in the elderly in developed countries and is particularly associated with age-related macular degeneration (AMD). Cabozantinib (CBZ) hinders the activation of multiple receptor tyrosine kinases involved in tumor angiogenesis, such as hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2). We aimed to investigate the role and mechanism of CBZ in a mouse laser-induced CNV model. In zebrafish embryos, CBZ perturbed intersegmental vessel (ISV) formation without obvious neurodevelopment impairment. In the mouse laser-induced CNV model, phosphorylated hepatocyte growth factor receptor (p-MET) and phosphorylated vascular endothelial growth factor receptor 2 (p-VEGFR2) were increased in the CNV region. CBZ intravitreal injection or oral gavage alleviated CNV leakage and the CNV lesion area without obvious intraocular toxicity, as well as disturbed the phosphorylation of MET and VEGFR2. Additionally, CBZ downregulated the expression of the hepatocyte growth factor (HGF) with no effect on the expression of the vascular endothelial growth factor (VEGF). CBZ downregulated HGF, p-MET, and p-VEGFR2 expressionsin vitro, as well as inhibited the proliferation, migration, and tube formation of b-End3 cells. In summary, CBZ alleviates mouse CNV formation possibly via inhibiting the activation of MET and VEGFR2. The findings provide a novel potential therapy method for CNV patients.
C1 [Zhang, Xiaoli; Xie, Laiqing; Xu, Jiaowen; Guo, Yang] Soochow Univ, Affiliated Hosp 2, Dept Ophthalmol, Suzhou, Jiangsu, Peoples R China.
   [Zhang, Xiaoli; Zhu, Manhui; Xu, Jiaowen; Guo, Yang; Song, E.] Soochow Univ, Lixiang Eye Hosp, Dept Ophthalmol, Suzhou, Jiangsu, Peoples R China.
   [Sun, Xiaodong; Xu, Xun] Shanghai Key Lab Ocular Fundus Dis, Shanghai, Peoples R China.
   [Sun, Xiaodong; Xu, Xun] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Sch Med, Dept Ophthalmol, Shanghai, Peoples R China.
   [Liu, Dong; Shi, Yunwei] Nantong Univ, Coinnovat Ctr Neuroregenerat, Jiangsu Key Lab Neuroregenerat, Nantong, Peoples R China.
C3 Soochow University - China; Soochow University - China; Shanghai Jiao
   Tong University; Nantong University
RP Song, E (通讯作者)，Soochow Univ, Lixiang Eye Hosp, Dept Ophthalmol, Suzhou, Jiangsu, Peoples R China.; Xu, X (通讯作者)，Shanghai Key Lab Ocular Fundus Dis, Shanghai, Peoples R China.
EM drxuxun@sjtu.edu.cn; songe@suda.edu.cn
OI Song, E/0000-0003-4259-9739
FU Suzhou Science and Technology Bureau [SS201426, SS201758, SYS2018004,
   SYS2018005]; Suzhou Commission of Health and Family Planning
   [KJXW2018076]; Jiangsu Distinguished Medical Experts Program (2016);
   Gusu Health Leading Talent Plan [025]
FX This work was supported by the Suzhou Science and Technology Bureau
   (Grant nos. SS201426, SS201758, SYS2018004, and SYS2018005), Suzhou
   Commission of Health and Family Planning (KJXW2018076), Jiangsu
   Distinguished Medical Experts Program (2016), and Gusu Health Leading
   Talent Plan (025).
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NR 51
TC 6
Z9 6
U1 3
U2 8
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 JUN 20
PY 2020
VL 2020
AR 5905269
DI 10.1155/2020/5905269
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MG6IJ
UT WOS:000546133000002
PM 32655941
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Liu, S
   Biesemeier, AK
   Tschulakow, AV
   Thakkar, HV
   Julien-Schraermeyer, S
   Schraermeyer, U
AF Liu, Shan
   Biesemeier, Antje K.
   Tschulakow, Alexander, V
   Thakkar, Harsh, V
   Julien-Schraermeyer, Sylvie
   Schraermeyer, Ulrich
TI A new rat model of treatment-naive quiescent choroidal
   neovascularization induced by human VEGF165 overexpression
SO BIOLOGY OPEN
LA English
DT Article
DE Choroidal neovascularization (CNV); Vascular endothelial growth factor
   (VEGF); Electron microscopy (EM); Bevacizumab; Angiogenesis; Age-related
   macular degeneration (AMD)
ID ENDOTHELIAL GROWTH-FACTOR; OPTICAL COHERENCE TOMOGRAPHY; RETINAL-PIGMENT
   EPITHELIUM; MACULAR DEGENERATION PATIENTS; IN-VIVO; ANIMAL-MODELS;
   INTRAVITREAL INJECTION; MEDIATED EXPRESSION; GEOGRAPHIC ATROPHY;
   IMAGE-ANALYSIS
AB Vascular endothelial growth factor (VEGF) is a crucial stimulator for choroidal neovascularization (CNV). Our aim was to develop a reproducible and valid treatment-naive quiescent CNV (i.e. without signs of exudation and with normal visual acuity) ratmodel bysubretinal injection of an adeno-associated virus (AAV)-VEGFA165 vector. The CNV development was longitudinally followed up in vivo by scanning laser ophthalmoscopy/optical coherence tomography, fluorescein and Indocyanine Green angiographies and ex vivo by electron microscopy (EM) and immunohistochemistry. In total, 57 eyes were analysed. In vivo, a quiescent CNV was observed in 93% of the eyes 6 weeks post-transduction. In EM, CNV vessels with few fenestrations, multi-layered basement membranes and bifurcation of endothelial cells were observed sharing the human CNV features. Human VEGF overexpression, multi-layered retinal pigment epithelium (RPE) (RPE65) and macrophages/activated microglia (Iba1) were also detected. In addition, 19 CNV eyes were treated for up to 3 weeks with bevacizumab. The retinal and CNV lesion thickness decreased significantly in bevacizumab-treated CNV eyes compared with untreated CNV eyes 1 week after the treatment. In conclusion, our experimental CNV resembles those seen in patients suffering from treatment-naive quiescent CNV in wet age-related macular degeneration (AMD), and responds to short-term treatment with bevacizumab. Our new model can, therefore, be used to test the long-term effect of new drugs targeting CNV under precisely-defined conditions.
C1 [Liu, Shan; Biesemeier, Antje K.; Tschulakow, Alexander, V; Thakkar, Harsh, V; Julien-Schraermeyer, Sylvie; Schraermeyer, Ulrich] Ctr Ophthalmol, Div Expt Vitreoretinal Surg, D-72076 Tubingen, Germany.
   [Biesemeier, Antje K.] Univ Tubingen, Nat & Med Inst, Appl Mat Sci & Electron Microscopy, D-72770 Reutlingen, Germany.
   [Tschulakow, Alexander, V; Thakkar, Harsh, V; Julien-Schraermeyer, Sylvie; Schraermeyer, Ulrich] STZ OcuTox Preclin Drug Assessment, D-72379 Hechingen, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Eberhard Karls University of Tubingen
RP Schraermeyer, U (通讯作者)，Ctr Ophthalmol, Div Expt Vitreoretinal Surg, D-72076 Tubingen, Germany.; Schraermeyer, U (通讯作者)，STZ OcuTox Preclin Drug Assessment, D-72379 Hechingen, Germany.
EM ulrich.schraermeyer@med.uni-tuebingen.de
OI Julien-Schraermeyer, Sylvie/0000-0002-2322-511X; Biesemeier,
   Antje/0000-0002-3462-8803; Schraermeyer, Ulrich/0000-0002-7969-8426
FU China Scholarship Council [201408080114]; Deutsche
   Forschungsgemeinschaft [BI 1551/3-1]; University of Tubingen
FX This work was supported by the China Scholarship Council [201408080114],
   and the Deutsche Forschungsgemeinschaft [BI 1551/3-1]. We acknowledge
   support by the Open Access Publishing Fund of the University of
   Tu<spacing diaeresis> bingen.
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NR 86
TC 3
Z9 3
U1 0
U2 0
PU COMPANY BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING, STATION RD, HISTON, CAMBRIDGE CB24 9LF, ENGLAND
SN 2046-6390
J9 BIOL OPEN
JI Biol. Open
PD JUN
PY 2020
VL 9
IS 6
AR bio048736
DI 10.1242/bio.048736
PG 17
WC Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics
GA PQ8KS
UT WOS:000606793000002
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Du, ZJ
   Zhang, W
   Wang, SY
   Zhang, J
   He, JG
   Wang, Y
   Dong, YH
   Huo, M
AF Du, Zhaojiang
   Zhang, Wen
   Wang, Shengyu
   Zhang, Jing
   He, Jingang
   Wang, Yuan
   Dong, Yuhong
   Huo, Min
TI Celastrol protects human retinal pigment epithelial cells against
   hydrogen peroxide mediated oxidative stress, autophagy, and apoptosis
   through sirtuin 3 signal pathway
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE autophagy; celastrol; oxidative stress; retinal pigment epithelial
   cells; sirtuin 3
ID MACULAR DEGENERATION; GANGLION-CELLS; DIABETIC-RATS; INFLAMMATION;
   PATHOGENESIS; DEACETYLASE; INHIBITION; SURVIVAL; MUSCLE; DEATH
AB Age-related macular degeneration (AMD), one of the most common causes of visual impairment, often occurrs in the elderly in developed countries. Oxidative stress, autophagy, and apoptosis of retinal pigment epithelial (RPE) cells play roles in the pathogenesis of AMD. In the current study, the protective effect of celastrol against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis was investigated using a human RPE cell line (ARPE-19). H2O2 inhibited ARPE-19 cells' survival and autophagy and induced their oxidative stress and apoptosis. Compared with the H2O2 group, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay showed that celastrol increased ARPE-19 cells' survival in a dose- and time-dependent manner. Further, studies have suggested that celastrol has antioxidative stress and antiapoptosis effects in H2O2-treated ARPE-19 cells. Also, cell autophagy is activated by celastrol in H2O2-treated ARPE-19 cells. Reverse transcription polymerase chain reaction and Western blot showed that celastrol elevated the messenger RNA (mRNA) and protein expression of sirtuin 3 (SIRT3) in H2O2-induced ARPE-19 cells. Inhibition of the level of SIRT3 by SIRT3 small interfering RNA (siRNA) reversed the effects of celastrol on oxidative stress, autophagy, and apoptosis in H2O2-induced ARPE-19 cells. In conclusion, these observations suggest that celastrol activates the SIRT3 pathway in RPE cells and protects against H2O2-induced oxidative stress and apoptosis.
C1 [Du, Zhaojiang; Zhang, Wen; Wang, Shengyu; Zhang, Jing; He, Jingang; Wang, Yuan; Dong, Yuhong; Huo, Min] Xian Cent Hosp, Dept Ophthalmol, 161 Xiwu Rd, Xian 710003, Shaanxi, Peoples R China.
RP Du, ZJ (通讯作者)，Xian Cent Hosp, Dept Ophthalmol, 161 Xiwu Rd, Xian 710003, Shaanxi, Peoples R China.
EM jiang_zhaodu@sina.com
FU Xi'an City Science & Technology Program Foundation in China.
   [201805097YX5SF31]; Shaanxi Provincial Science & Technology Program
   Foundation in China [2017SF-213]
FX Xi'an City Science & Technology Program Foundation in China.,
   Grant/Award Number: (201805097YX5SF31); Shaanxi Provincial Science &
   Technology Program Foundation in China, Grant/Award Number: (2017SF-213)
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NR 49
TC 11
Z9 12
U1 0
U2 16
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-2312
EI 1097-4644
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD JUN
PY 2019
VL 120
IS 6
BP 10413
EP 10420
DI 10.1002/jcb.28326
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA HX1FO
UT WOS:000467135600156
PM 30618198
DA 2022-11-30
ER

PT J
AU Nashine, S
   Cohen, P
   Nesburn, AB
   Kuppermann, BD
   Kenney, MC
AF Nashine, Sonali
   Cohen, Pinchas
   Nesburn, Anthony B.
   Kuppermann, Baruch D.
   Kenney, M. Cristina
TI Characterizing the protective effects of SHLP2, a mitochondrial-derived
   peptide, in macular degeneration
SO SCIENTIFIC REPORTS
LA English
DT Article
ID OXIDATIVE STRESS; AMYLOID-BETA; HUMANIN; DYSFUNCTION; EPITHELIUM; CELLS
AB Mitochondrial-derived peptides (MDPs) are rapidly emerging therapeutic targets to combat development of neurodegenerative diseases. SHLP2 (small humanin-like peptide 2) is a newly discovered MDP that is coded from the MT-RNR2 (Mitochondrially encoded 16S rRNA) gene in mitochondrial DNA (mtDNA). In the current study, we examined the biological consequences of treatment with exogenously-added SHLP2 in an in vitro human transmitochondrial age-related macular degeneration (AMD) ARPE-19 cell model. In AMD cells, we observed significant down-regulation of the MDP-coding MT-RNR2 gene, and remarkably reduced levels of all five oxidative phosphorylation (OXPHOS) complex I-V protein subunits that are involved in the electron transport chain; these results suggested mitochondrial toxicity and abnormal OXPHOS complex protein subunits' levels in AMD cells. However, treatment of AMD cells with SHLP2: (1) restored the normal levels of OXPHOS complex protein subunits, (2) prevented loss of viable cells and mitochondria, (3) increased the number of mtDNA copies, (4) induced anti-apoptotic effects, and (5) attenuated amyloid-beta-induced cellular and mitochondrial toxicity. Cumulatively, our findings established the protective role of SHLP2 in AMD cells in vitro. In conclusion, this novel study supports the merit of SHLP2 in the treatment of AMD, a primary retinal disease that is a leading cause of blindness among the elderly population in the United States as well as worldwide.
C1 [Nashine, Sonali; Nesburn, Anthony B.; Kuppermann, Baruch D.; Kenney, M. Cristina] Univ Calif Irvine, Dept Ophthalmol, Gavin Herbert Eye Inst, Irvine, CA 92697 USA.
   [Cohen, Pinchas] Univ Southern Calif, Leonard Davis Sch Gerontol, Los Angeles, CA USA.
   [Nesburn, Anthony B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   [Kenney, M. Cristina] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA.
C3 University of California System; University of California Irvine;
   University of Southern California; Cedars Sinai Medical Center;
   University of California System; University of California Irvine
RP Kenney, MC (通讯作者)，Univ Calif Irvine, Dept Ophthalmol, Gavin Herbert Eye Inst, Irvine, CA 92697 USA.; Kenney, MC (通讯作者)，Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA.
EM mkenney@uci.edu
RI NASHINE, SONALI/AAG-1474-2020
FU 2017 Genentech/ARVO AMD Translational Research Fellowship; RPB (Research
   to Prevent Blindness) pilot research grant; Arnold and Mabel Beckman
   Foundation; UCI School of Medicine; Discovery Eye Foundation; Guenther
   Foundation; Beckman Initiative for Macular Research; Polly and Michael
   Smith Foundation; Max Factor Family Foundation; Iris and B. Gerald
   Cantor Foundation; RPB; NATIONAL INSTITUTE ON AGING [P01AG055369]
   Funding Source: NIH RePORTER
FX This research work was supported by the 2017 Genentech/ARVO AMD
   Translational Research Fellowship, RPB (Research to Prevent Blindness)
   pilot research grant, Arnold and Mabel Beckman Foundation, UCI School of
   Medicine, Discovery Eye Foundation, Guenther Foundation, Beckman
   Initiative for Macular Research, Polly and Michael Smith Foundation, Max
   Factor Family Foundation, Iris and B. Gerald Cantor Foundation; research
   was supported in part by an unrestricted grant from RPB. SN, an Arnold
   and Mabel Beckman Postdoctoral fellow, is a recipient of the 2017
   Genentech/ARVO AMD Translational Research Fellowship and the RPB pilot
   research grant.
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NR 29
TC 36
Z9 37
U1 0
U2 4
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD OCT 11
PY 2018
VL 8
AR 15175
DI 10.1038/s41598-018-33290-5
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GW6PS
UT WOS:000447083100066
PM 30310092
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Schnabolk, G
   Parsons, N
   Obert, E
   Annamalai, B
   Nasarre, C
   Tomlinson, S
   Lewin, AS
   Rohrer, B
AF Schnabolk, Gloriane
   Parsons, Nathaniel
   Obert, Elisabeth
   Annamalai, Balasubramaniam
   Nasarre, Cecile
   Tomlinson, Stephen
   Lewin, Alfred S.
   Rohrer, Barbel
TI Delivery of CR2-fH Using AAV Vector Therapy as Treatment Strategy in the
   Mouse Model of Choroidal Neovascularization
SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
LA English
DT Article
ID COMPLEMENT FACTOR-H; PIGMENT EPITHELIAL-CELLS; RESTORES CONE FUNCTION;
   MEDIATED GENE-THERAPY; MACULAR DEGENERATION; ALTERNATIVE PATHWAY;
   TARGETED INHIBITOR; OXIDATIVE STRESS; FACTOR-B; INJURY
AB Complement activation plays a significant role in age-related macular degeneration (AMD) pathogenesis, and polymorphisms interfering with factor H (fH) function, a complement alternative pathway (AP) inhibitor, are associated with increased AMD risk. We have previously validated an AP inhibitor, a fusion protein consisting of a complement receptor 2 fragment linked to the inhibitory domain of fH (CR2-fH) as an efficacious treatment for choroidal neovascularization (CNV) when delivered intravenously. Here we tested an alternative approach of AAV-mediated delivery (AAV5-VMD2-CR2-fH or AAV5-VMD2-mCherry) using subretinal delivery in C57BL/6J mice. Secretion of CR2-fH was confirmed in polarized retinal pigment epithelium (RPE) cells. A safe concentration of AAV5-VMD2-CR2-fH was identified using electroretinography, optical coherence tomography (OCT), RPE morphology, and antibody profiling. One month after gene delivery, CNV was induced using argon laser photocoagulation. OCT assessment demonstrated reduced CNV with AAV5-VMD2-CR2-fH administration. Bioavailability studies revealed that gene-therapy delivered similar levels of CR2-fH to the RPE/choroid as treatment by intravenous injections, and C3a ELISA verified reduced CNV-associated ocular C3a production. These results contribute to existing data illustrating the importance of the AP of complement in CNV development and its potential role in AMD treatment. Demonstration of AAV-vector efficacy opens new avenues for the development of treatment strategies.
C1 [Schnabolk, Gloriane; Parsons, Nathaniel; Obert, Elisabeth; Annamalai, Balasubramaniam; Nasarre, Cecile; Rohrer, Barbel] Med Univ South Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
   [Tomlinson, Stephen] Med Univ South Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
   [Tomlinson, Stephen; Rohrer, Barbel] Ralph H Johnson VA Med Ctr, Div Res, Charleston, SC 29401 USA.
   [Lewin, Alfred S.] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL 32611 USA.
C3 Medical University of South Carolina; Medical University of South
   Carolina; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); Ralph H Johnson VA Medical Center; State
   University System of Florida; University of Florida
RP Schnabolk, G; Rohrer, B (通讯作者)，Med Univ South Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
EM faith@musc.edu; rohrer@musc.edu
OI Lewin, Alfred/0000-0002-4192-9727
FU Department of Veterans Affairs [RX000444, 1I01RX001141, 1I21RX002363];
   NIH [R01 EY019320, R01 EY024581, R01 EY026268, P30 EY02172, R01
   DK102912, C06 RR015455]; NATIONAL CENTER FOR RESEARCH RESOURCES
   [C06RR015455] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R01EY026268, P30EY021721, R01EY019320, R01EY024581] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY
   DISEASES [R01DK102912] Funding Source: NIH RePORTER; Veterans Affairs
   [I01RX000444, I01RX001141, I01BX003050, I21RX002363] Funding Source: NIH
   RePORTER
FX Funding for this project was provided in part by the Department of
   Veterans Affairs merit awards RX000444 (to B.R.) and 1I01RX001141 and
   1I21RX002363 (to S.T.) and the NIH R01 EY019320 and R01 EY024581 (to
   B.R.), R01 EY026268 and P30 EY02172 (A.S.L.), and R01 DK102912 (S.T.).
   Animal studies were conducted in a facility constructed with support
   from the NIH (C06 RR015455).
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NR 63
TC 18
Z9 19
U1 1
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 2329-0501
J9 MOL THER-METH CLIN D
JI Mol.Ther.-Methods Clin. Dev.
PD JUN
PY 2018
VL 9
BP 1
EP 11
DI 10.1016/j.omtm.2017.11.003
PG 11
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA GJ5VX
UT WOS:000435452300001
PM 29234687
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, YY
   Zhang, DD
   Tang, ZM
   Zhang, Y
   Gao, HQ
   Ni, N
   Shen, BQ
   Sun, H
   Gu, P
AF Wang, Yuyao
   Zhang, Dandan
   Tang, Zhimin
   Zhang, Yi
   Gao, Huiqin
   Ni, Ni
   Shen, Bingqiao
   Sun, Hao
   Gu, Ping
TI REST, regulated by RA through miR-29a and the proteasome pathway, plays
   a crucial role in RPC proliferation and differentiation
SO CELL DEATH & DISEASE
LA English
DT Article
ID RETINAL PROGENITOR CELLS; EMBRYONIC STEM-CELLS; ROD PHOTORECEPTOR
   DIFFERENTIATION; SCF-BETA-TRCP; IN-VITRO; NEURONAL DIFFERENTIATION;
   GENE-EXPRESSION; NEURAL DIFFERENTIATION; PRIMARY NEUROGENESIS;
   SELF-RENEWAL
AB One of the primary obstacles in the application of retinal progenitor cells (RPCs) to the treatment of retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), is their limited ability to proliferate and differentiate into specific retinal neurons. In this study, we revealed that repressor element-1-silencing transcription factor (REST), whose expression could be transcriptionally and post-transcriptionally mediated by retinoic acid (RA, one isomeride of a vitamin A derivative used as a differentiation-inducing agent in many disease treatments), plays a pivotal role in the regulation of proliferation and differentiation of RPCs. Our results show that direct knockdown of endogenous REST reduced RPC proliferation but accelerated RPC differentiation toward retinal neurons, which phenocopied the observed effects of RA on RPCs. Further studies disclosed that the expression level of REST could be downregulated by RA not only through upregulating microRNA (miR)-29a, which directly interacted with the 3'-untranslated region (3'-UTR) of the REST mRNA, but also through promoting REST proteasomal degradation. These results show us a novel functional protein, REST, which regulates RPC proliferation and differentiation, can be mediated by RA. Understanding the mechanisms of REST and RA in RPC fate determination enlightens a promising future for the application of REST and RA in the treatment of retinal degeneration diseases.
C1 [Wang, Yuyao; Zhang, Dandan; Tang, Zhimin; Zhang, Yi; Gao, Huiqin; Ni, Ni; Shen, Bingqiao; Sun, Hao; Gu, Ping] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Ophthalmol, Shanghai 200011, Peoples R China.
   [Wang, Yuyao; Zhang, Dandan; Tang, Zhimin; Zhang, Yi; Gao, Huiqin; Ni, Ni; Shen, Bingqiao; Sun, Hao; Gu, Ping] Shanghai Key Lab Orbital Dis & Ocular Oncol, Shanghai 200011, Peoples R China.
C3 Shanghai Jiao Tong University
RP Shen, BQ; Sun, H; Gu, P (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Ophthalmol, Shanghai 200011, Peoples R China.; Shen, BQ; Sun, H; Gu, P (通讯作者)，Shanghai Key Lab Orbital Dis & Ocular Oncol, Shanghai 200011, Peoples R China.
EM shenbingqiao.123@163.com; sunhao6666@126.com; guping2009@126.com
RI Sun, Hao/AAX-1653-2020
FU Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant
   Support [20161316]; National Natural Science Foundations of China
   [81570883, 31500835]; Science and Technology Commission of Shanghai
   [17DZ2260100]
FX The research was supported by Shanghai Municipal Education
   Commission-Gaofeng Clinical Medicine Grant Support (20161316), the
   National Natural Science Foundations of China (81570883 and 31500835)
   and The Science and Technology Commission of Shanghai (17DZ2260100).
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NR 59
TC 10
Z9 10
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD APR 18
PY 2018
VL 9
AR 444
DI 10.1038/s41419-018-0473-5
PG 15
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA GF2OP
UT WOS:000431779800006
PM 29670089
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Kwon, JW
   Jee, D
   La, TY
AF Kwon, Jin-woo
   Jee, Donghyun
   La, Tae Yoon
TI The association between myocardial infarction and intravitreal
   bevacizumab injection
SO MEDICINE
LA English
DT Article
DE age-related macular degeneration; bevacizumab; intravitreal injection;
   myocardial infarction; retinal vein occlusion
ID ENDOTHELIAL GROWTH-FACTOR; PROLIFERATIVE DIABETIC-RETINOPATHY;
   BLOOD-RETINAL BARRIER; ARTERIAL THROMBOEMBOLIC EVENTS; MACULAR
   DEGENERATION; RISK-FACTORS; ADVERSE EVENTS; PLASMA-LEVELS; RANIBIZUMAB;
   EDEMA
AB To evaluate the risk of myocardial infarction (MI) after receiving intravitreal bevacizumab (IVB) injection. We retrospectively reviewed the charts of patients who had received IVB injection in 2016, and grouped them according to whether they received the injection for age-related macular degeneration (AMD), diabetes-related complications, or retinal vein occlusion (RVO). We then investigated the prevalence of MI within 2 months after IVB injection and analyzed the possible association of IVB with MI. During 2016, 724 patients were enrolled and received a total of 1870 IVB injections. Seven patients were diagnosed with MI within 2 months after receiving an IVB injection. Of 274 patients with AMD, 2 were diagnosed with MI; of 311 patients with diabetes-related complications, 3 were diagnosed with MI; and of 139 patients with RVO, 2 were diagnosed with MI (P=0.785). All MIs occurred between 3 days and 3 weeks after IVB injection (mean=14.00 +/- 6.45 days). The MIs after receiving IVB were associated with previous history of MI or cerebrovascular infarction in multivariate logistic regression analysis (P=0.005). There was no significant difference in MI prevalence after IVB injection according to the reason for receiving the injection. However, care should be taken when administering IVB injections, especially to patients with risk factors such as history of MI or cerebrovascular infarction.
C1 [Kwon, Jin-woo; Jee, Donghyun; La, Tae Yoon] Catholic Univ Korea, Coll Med, St Vincents Hosp, Dept Ophthalmol & Visual Sci, 93 Jungbu Daero, Suwon 16247, Kyunggi Do, South Korea.
C3 Catholic University of Korea
RP Jee, D; La, TY (通讯作者)，Catholic Univ Korea, Coll Med, St Vincents Hosp, Dept Ophthalmol & Visual Sci, 93 Jungbu Daero, Suwon 16247, Kyunggi Do, South Korea.
EM doj087@mail.harvard.edu; laty@catholic.ac.kr
OI Kwon, Jin-woo/0000-0003-2093-4284
FU National Research Foundation of Korea Grant - Korean government (MSIP)
   [NRF-2016R1D1A1B03932606]
FX The authors acknowledge the financial support of the National Research
   Foundation of Korea Grant funded by the Korean government (MSIP) (No
   NRF-2016R1D1A1B03932606).
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NR 55
TC 5
Z9 5
U1 0
U2 1
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 MAR
PY 2018
VL 97
IS 13
AR e0198
DI 10.1097/MD.0000000000010198
PG 4
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA GC0CJ
UT WOS:000429444000029
PM 29595656
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Santos-Ferreira, T
   Postel, K
   Stutzki, H
   Kurth, T
   Zeck, G
   Ader, M
AF Santos-Ferreira, Tiago
   Postel, Kai
   Stutzki, Henrike
   Kurth, Thomas
   Zeck, Gunther
   Ader, Marius
TI Daylight Vision Repair by Cell Transplantation
SO STEM CELLS
LA English
DT Article
DE Retinal degeneration; Transplantation; Cone-like photoreceptor;
   Nrl-deficient mouse; Microelectrode array
ID PHOTORECEPTOR PRECURSORS; RETINAL DEGENERATION; CORRELATIVE LIGHT;
   SURFACE ANTIGEN; VISUAL FUNCTION; GENE-THERAPY; STEM-CELLS; MOUSE;
   INTEGRATION; CONE
AB Human daylight vision depends on cone photoreceptors and their degeneration results in visual impairment and blindness as observed in several eye diseases including age-related macular degeneration, cone-rod dystrophies, or late stage retinitis pigmentosa, with no cure available. Preclinical cell replacement approaches in mouse retina have been focusing on rod dystrophies, due to the availability of sufficient donor material from the rod-dominated mouse retina, leaving the development of treatment options for cone degenerations not well studied. Thus, an abundant and traceable source for donor cone-like photoreceptors was generated by crossing neural retina leucine zipper-deficient (Nrl(-/-)) mice with an ubiquitous green fluorescent protein (GFP) reporter line resulting in double transgenic tg(Nrl(-/-); aGFP) mice. In Nrl(-/-) retinas, all rods are converted into cone-like photoreceptors that express CD73 allowing their enrichment by CD73-based magnetic activated cell sorting prior transplantation into the subretinal space of adult wild-type, cone-only (Nrl(-/-)), or cone photoreceptor function loss 1 (Cpfl1) mice. Donor cells correctly integrated into host retinas, acquired mature photoreceptor morphology, expressed cone-specific markers, and survived for up to 6 months, with significantly increased integration rates in the cone-only Nrl(-/-) retina. Individual retinal ganglion cell recordings demonstrated the restoration of photopic responses in cone degeneration mice following transplantation suggesting, for the first time, the feasibility of daylight vision repair by cell replacement in the adult mammalian retina.
C1 [Santos-Ferreira, Tiago; Postel, Kai; Kurth, Thomas; Ader, Marius] Tech Univ Dresden, CRTD DFG Ctr Regenerat Therapies Dresden, D-01307 Dresden, Germany.
   [Stutzki, Henrike; Zeck, Gunther] Univ Tubingen, Natl & Med Sci Inst, Reutlingen, Germany.
   [Stutzki, Henrike] Grad Training Ctr Neurosci, Tubingen, Germany.
C3 Technische Universitat Dresden; Eberhard Karls University of Tubingen
RP Ader, M (通讯作者)，Tech Univ Dresden, CRTD DFG Ctr Regenerat Therapies Dresden, Fetscherstrasse 105, D-01307 Dresden, Germany.
EM marius.ader@crt-dresden.de
RI Zeck, Günther/H-7419-2013; Ader, Marius/E-7535-2010
OI Zeck, Günther/0000-0003-3998-9883; Ader, Marius/0000-0001-9467-7677;
   Kurth, Thomas/0000-0001-5624-1717; Ferreira, Tiago/0000-0002-2065-6440
FU Deutsche Forschungsgemeinschaft (DFG) [FZT 111, AD375/3-1, Grant 041_
   296318]; Fundacao para a Ciencia e a Tecnologia (FCT)
   [SFRH/BD/60787/2009]
FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG) FZT
   111 (Center for Regenerative Therapies Dresden, Cluster of Excellence),
   DFG Grant AD375/3-1, DFG Sonderforschungsbereich 655 " From cells into
   tissue" (Grant 041_ 296318), the Fundacao para a Ciencia e a Tecnologia
   (FCT: SFRH/BD/60787/2009), and the ProRetina Stiftung. We thank Anand
   Swaroop and Sandra Cottet for providing Nr2/2 mice, Bernd Wissinger for
   providing Cpfl1 mice, Wolfgang Baehr for cone arrestin antibody, Jochen
   Haas and Susanne Kretschmar for technical support, and Sindy Bohme,
   Emily Lessmann, and Katrin Baumgart for animal husbandry.
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NR 50
TC 74
Z9 76
U1 1
U2 35
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD JAN
PY 2015
VL 33
IS 1
BP 79
EP 90
DI 10.1002/stem.1824
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA AW8ES
UT WOS:000346494100009
PM 25183393
OA Bronze
DA 2022-11-30
ER

PT J
AU Richer, S
   Patel, S
   Sockanathan, S
   Ulanski, LJ
   Miller, L
   Podella, C
AF Richer, Stuart
   Patel, Shana
   Sockanathan, Shivani
   Ulanski, Lawrence J., II
   Miller, Luke
   Podella, Carla
TI Resveratrol Based Oral Nutritional Supplement Produces Long-Term
   Beneficial Effects on Structure and Visual Function in Human Patients
SO NUTRIENTS
LA English
DT Article
DE epigenetics; visual structure and function; resveratrol; Longevinex (R);
   age-related macular degeneration; ophthalmology
ID LONGEVINEX; EXPRESSION; THICKNESS
AB Background: Longevinex (R) (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. Methods: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). Results: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient's pathophysiology. No side effects were observed. Conclusions: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities.
C1 [Richer, Stuart; Ulanski, Lawrence J., II; Podella, Carla] Captain James A Lovell Fed Hlth Care Ctr, Eye Clin 112E, N Chicago, IL 60064 USA.
   [Richer, Stuart; Ulanski, Lawrence J., II] Univ Illinois, Eye & Ear Infirm, Chicago, IL 60612 USA.
   [Richer, Stuart; Patel, Shana; Sockanathan, Shivani; Miller, Luke] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, N Chicago, IL 60064 USA.
C3 University of Illinois System; University of Illinois Chicago;
   University of Illinois Chicago Hospital; Chicago Medical School;
   Rosalind Franklin University Medical & Science
RP Richer, S (通讯作者)，Captain James A Lovell Fed Hlth Care Ctr, Eye Clin 112E, 3001 Green Bay Rd, N Chicago, IL 60064 USA.
EM stuart.richer1@va.gov; shana.patel@my.rfums.org;
   shivani.sockanathan@my.rfums.org; larry.ulanski@gmail.com;
   luke.miller@my.rfums.org; cjpstella63@gmail.com
FU Resveratrol Partners LCC (Las Vegas, NV, USA) makers of Longevinex(R)
   capsules
FX Resveratrol Partners LCC (Las Vegas, NV, USA) makers of Longevinex (R)
   capsules provided clinical research lab development funding. Stuart
   Richer has no direct commercial or financial interest. The following
   companies also supplied equipment to the Ocular Preventive Medicine
   Laboratory: Stereo Optical Inc. (Chicago, IL, USA) and RTVue OptoVue
   Inc. (Freemont, CA, USA).
CR Barger JL, 2008, EXP GERONTOL, V43, P859, DOI 10.1016/j.exger.2008.06.013
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NR 27
TC 39
Z9 39
U1 0
U2 15
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-6643
J9 NUTRIENTS
JI Nutrients
PD OCT
PY 2014
VL 6
IS 10
BP 4404
EP 4420
DI 10.3390/nu6104404
PG 17
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA AS6FP
UT WOS:000344360200023
PM 25329968
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Shimada, N
   Ohno-Matsui, K
   Iseki, S
   Koike, M
   Uchiyama, Y
   Wang, JY
   Yoshida, T
   Sato, T
   Peters, C
   Mochizuki, M
   Morita, I
AF Shimada, Noriaki
   Ohno-Matsui, Kyoko
   Iseki, Sachiko
   Koike, Masato
   Uchiyama, Yasuo
   Wang, Jiying
   Yoshida, Takeshi
   Sato, Tetsuji
   Peters, Christoph
   Mochizuki, Manabu
   Morita, Ikuo
TI Cathepsin L in Bone Marrow-Derived Cells Is Required for Retinal and
   Choroidal Neovascularization
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID GROWTH-FACTOR THERAPY; ENDOTHELIAL-CELLS; PROGENITOR CELLS
AB Many vision-threatening diseases are characterized by intraocular neovascularization, (e.g., proliferative diabetic retinopathy and age-related macular degeneration). Although a new therapy with anti-VEGF antibodies is being used to treat these intraocular neovascular disorders, the visual recovery is limited, mainly because of the remnants of fibrovascular tissues. The ideal goal of the treatment is to prevent the invasion of new vessels into the avascular tissue through a matrix barrier. The purpose of this study was to determine the role played by cathepsin L, a matrix degrading enzyme, on intraocular angiogenesis. Used established animal models of retinal and choroidal neovascularization, we demonstrated that an inhibition of cathepsin L by specific inhibitors resulted in a significant decrease of intraocular neovascularization. A similar decrease of neovascularization was found in cathepsin L-deficient mice. Transplantation of bone marrow from cathepsin L-deficient mice into wild-type mice significantly reduced the degree of intraocular neovascularization. In addition, immunocytochemical analyses demonstrated that YE cadherin-positive endothelial progenitor cells, but not CD43-positive or Iba-1positive cells, were the major cells contributing to the production of cathepsin L These data indicate that cathepsin L expressed in endothelial progenitor cells plays a critical role in intraocular angiogenesis and suggest a potential therapeutic approach of targeting cathepsin L for neovascular ocular diseases. (Am J Pathol 2010, 1762571-2580; DOI 10.2353/ajpath.2010.091027)
C1 [Ohno-Matsui, Kyoko] Tokyo Med & Dent Univ, Dept Ophthalmol & Visual Sci, Bunkyo Ku, Tokyo 113, Japan.
   [Iseki, Sachiko] Tokyo Med & Dent Univ, Dept Craniofacial Embryol, Tokyo 113, Japan.
   [Morita, Ikuo] Tokyo Med & Dent Univ, Sect Cellular Physiol Chem, Tokyo 113, Japan.
   [Koike, Masato; Uchiyama, Yasuo] Juntendo Univ, Grad Sch Med, Dept Cell Biol & Neurosci, Tokyo, Japan.
   [Sato, Tetsuji] Tsurumi Univ, Dept Anat, Sch Dent Med, Yokohama, Kanagawa, Japan.
   [Peters, Christoph] Univ Freiburg, Inst Mol Med & Cell Res, Freiburg, Germany.
C3 Tokyo Medical & Dental University (TMDU); Tokyo Medical & Dental
   University (TMDU); Tokyo Medical & Dental University (TMDU); Juntendo
   University; Tsurumi University; University of Freiburg
RP Ohno-Matsui, K (通讯作者)，Tokyo Med & Dent Univ, Dept Ophthalmol & Visual Sci, Bunkyo Ku, 1-5-45 Yushima, Tokyo 113, Japan.
EM k.ohno.oph@tmd.ac.jp
RI Koike, Masato/F-9584-2010
OI Koike, Masato/0000-0002-3174-5684
FU Japan Society for the Promotion of Science, Tokyo, Japan [17659654,
   19390441, 19659445, 20659306]
FX Supported in part by research grant 17659654, 19390441, 19659445, and
   20659306 from the Japan Society for the Promotion of Science, Tokyo,
   Japan.
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NR 25
TC 17
Z9 20
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD MAY
PY 2010
VL 176
IS 5
BP 2571
EP 2580
DI 10.2353/ajpath.2010.091027
PG 10
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 627XV
UT WOS:000280078600051
PM 20304958
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Kabanarou, SA
   Rubin, GS
AF Kabanarou, Stamatina A.
   Rubin, Gary S.
TI Reading with central scotomas: Is there a binocular gain?
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE AMD; reading; eye movements; binocular vision
ID AGE-RELATED MACULOPATHY; VISUAL-ACUITY MEASUREMENTS; MACULAR
   DEGENERATION; LOW-VISION; CONTRAST SENSITIVITY; EYE-MOVEMENTS;
   IMPAIRMENT; PSYCHOPHYSICS; DISABILITY; SUMMATION
AB Purpose. The purpose of this study was to compare reading performance under binocular versus monocular viewing conditions in patients with bilateral age-related macular degeneration (AMD).
   Methods. Twenty-two patients with AMD participated. Distance acuity, reading acuity, and contrast sensitivity were recorded binocularly and monocularly with the better eye. An infrared eye tracker recorded eye movements during reading. Reading speed and reading eye movement parameters, including number of fixations and regressions, fixation duration, and number of saccades to find the next line, were calculated for both viewing conditions. The difference between binocular and monocular performance (binocular gain) was computed. Regression analysis was used to determine whether intraocular differences in distance and reading acuity and contrast sensitivity were predictive of binocular gain.
   Results. Reading speed when using both eyes was highly correlated with the reading speed for the better eye. There was a small, but not significant, advantage of binocular viewing (6.9 words/minute, p = 0.33). No significant difference was detected in any eye movement parameters when comparing both eyes with the better eye. Although some patients showed either positive or negative binocular gain, the amount of gain was not predicted by intraocular differences in acuity or contrast sensitivity.
   Conclusions. Overall, there was no significant difference between binocular and monocular reading performance in patients with AMD.
C1 Inst Ophthalmol, Dept Vis Rehabil, London EC1V 9EL, England.
C3 University of London; University College London
RP Kabanarou, SA (通讯作者)，Inst Ophthalmol, Dept Vis Rehabil, 11-43 Bath St, London EC1V 9EL, England.
EM stamatina_k@hotmail.com
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NR 35
TC 25
Z9 25
U1 0
U2 11
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 NOV
PY 2006
VL 83
IS 11
BP 789
EP 796
DI 10.1097/01.opx.0000238642.65218.64
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 108VV
UT WOS:000242268200002
PM 17106405
DA 2022-11-30
ER

PT J
AU Becker, KCD
   Becker, RC
AF Becker, KCD
   Becker, RC
TI Nucleic acid aptamers as adjuncts to vaccine development
SO CURRENT OPINION IN MOLECULAR THERAPEUTICS
LA English
DT Article
DE immunomodulation; nucleic acid aptamers; vaccines
ID IN-VITRO SELECTION; RNA APTAMERS; AUTOMATED SELECTION; DNA; BINDING;
   GENERATION; STRATEGIES; MOLECULE; BLOCKING; PROGRESS
AB Nucleic acid 'aptamers', a term derived from the Latin word aptus, 'to fit', are RNA or DNA oligonucleotides that conform to the three-dimensional structure of a selected protein, peptide or small molecules' functional moiety. The 'lock and key' relationship between aptamers and their binding partner permits distinction between closely related but non-identical members of a protein family, or between different functional or conformational states of the same protein. This, along with other properties, separates aptamers from antibodies - the most popular class of molecular recognition tool for the past three decades.
   Despite the chemical, biological and manufacturing advantages offered by nucleic acid aptamers in a wide variety of conditions, and their generation against a range of clinically relevant targets, including growth factors, transcription factors and coagulation proteins, by two dozen or more companies devoted to the technology platform, only one aptamer, developed for the treatment of wet age-related macular degeneration, is currently available for use in humans. Nevertheless, phase I and II clinical trials for several indications are proceeding with considerable enthusiasm.
   The potential application of nucleic acid aptamers in novel arenas, including molecular imaging, vaccine development, immunomodulation, decoys for natural RNA-binding events, antiviral therapeutics and both cancer prophylaxis and treatment, is emerging with a pioneering mentality destined to change the paradigm of patient care.
C1 Duke Univ, Med Ctr, Dept Med, Duke Univ Sch Med, Durham, NC 27710 USA.
   Boston Univ, Coll Arts & Sci, Boston, MA 02215 USA.
C3 Duke University; Boston University
RP Becker, RC (通讯作者)，Duke Univ, Med Ctr, Dept Med, Duke Univ Sch Med, Durham, NC 27710 USA.
EM Becke021@mc.duke.edu
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NR 39
TC 8
Z9 8
U1 0
U2 6
PU THOMSON REUTERS (SCIENTIFIC) LTD
PI LONDON
PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND
SN 1464-8431
EI 2040-3445
J9 CURR OPIN MOL THER
JI Curr. Opin. Mol. Ther.
PD APR
PY 2006
VL 8
IS 2
BP 122
EP 129
PG 8
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA 025RT
UT WOS:000236285300006
PM 16610764
DA 2022-11-30
ER

PT J
AU Bosch, T
AF Bosch, T
TI Therapeutic apheresis - State of the art in the year 2005
SO THERAPEUTIC APHERESIS AND DIALYSIS
LA English
DT Article
DE dilative cardiomyopathy; immunoadsorption; LDL-apheresis; leukocyte
   apheresis; therapeutic apheresis
ID LOW-DENSITY-LIPOPROTEIN; BLOOD PURIFICATION; ALBUMIN DIALYSIS;
   LIVER-FAILURE; DILATED CARDIOMYOPATHY; CARDIAC DYSFUNCTION;
   ULCERATIVE-COLITIS; CONTROLLED-TRIAL; POTENTIAL ROLE; LDL-APHERESIS
AB Therapeutic apheresis is an extracorporeal blood purification method for the treatment of diseases in which pathological proteins or cells have to be eliminated. Selective plasma processing is more efficient in pathogen removal than unselective plasma exchange and does not require a substitution fluid like albumin. This overview presents the various selective devices for the treatment of plasma (plasmapheresis) and blood cells (leukocyte apheresis). Prospective randomized trials were performed for the treatment of age-related macular degeneration (Rheopheresis), sudden hearing loss (heparin-induced lipoprotein precipitation [HELP]), rheumatoid arthritis (Prosorba), dilative cardiomyopathy (Ig-Therasorb, Immunosorba), acute-on-chronic liver failure (molecular adsorbent recirculating system [MARS]), and ulcerative colitis (Cellsorba). Prospective non-randomized controlled trials were carried out treating hypercholesterolemia (Liposorber) and crossmatch-positive recipients before kidney transplantation (Immunosorba). Uncontrolled studies were done for ABO-incompatibility in living donor kidney transplantation (KT) (Glycosorb), acute humoral rejection after KT (Immunosorba) and acute liver failure (Prometheus). According to the 2002 International Apheresis Registry covering 11428 sessions in 811 patients. 79% of the patients showed an improvement of their condition by apheresis and only a few sessions were fraught with adverse effects (AE). The major AE were blood access difficulties (3.1%) and hypotension (1.6%). In summary, therapeutic apheresis is a safe and effective procedure for the treatment of diseases refractory to drug therapy.
C1 Univ Hosp Munich Grosshadern, Dept Internal Med 1, Div Nephrol, D-81366 Munich, Germany.
C3 University of Munich
RP Bosch, T (通讯作者)，Univ Hosp Munich Grosshadern, Dept Internal Med 1, Div Nephrol, D-81366 Munich, Germany.
EM thomas.bosch@med.uni-muenchen.de
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NR 49
TC 56
Z9 59
U1 0
U2 18
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1744-9979
EI 1744-9987
J9 THER APHER DIAL
JI Ther. Apher. Dial.
PD DEC
PY 2005
VL 9
IS 6
BP 459
EP 468
DI 10.1111/j.1744-9987.2005.00306.x
PG 10
WC Hematology; Urology & Nephrology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Hematology; Urology & Nephrology
GA 003QS
UT WOS:000234697300002
PM 16354277
DA 2022-11-30
ER

PT J
AU Ramshekar, A
   Bretz, CA
   Kunz, E
   Cung, T
   Richards, BT
   Stoddard, GJ
   Hageman, GS
   Chaqour, B
   Hartnett, ME
AF Ramshekar, Aniket
   Bretz, Colin A.
   Kunz, Eric
   Cung, Thaonhi
   Richards, Burt T.
   Stoddard, Gregory J.
   Hageman, Gregory S.
   Chaqour, Brahim
   Hartnett, M. Elizabeth
TI Role of Erythropoietin Receptor Signaling in Macrophages or Choroidal
   Endothelial Cells in Choroidal Neovascularization
SO BIOMEDICINES
LA English
DT Article
DE EPOR; EPO; CNV; AMD; CECs; macrophages
ID MACULAR DEGENERATION; ACTIVATION; EXPRESSION; DISEASE; STAT3; MODEL;
   GENE
AB Erythropoietin (EPO) has been proposed to reduce the progression of atrophic age-related macular degeneration (AMD) due to its potential role in neuroprotection. However, overactive EPO receptor (EPOR) signaling increased laser-induced choroidal neovascularization (CNV) and choroidal macrophage number in non-lasered mice, which raised the question of whether EPOR signaling increased CNV through the recruitment of macrophages to the choroid that released pro-angiogenic factors or through direct angiogenic effects on endothelial cells. In this study, we addressed the hypothesis that EPOR signaling increased CNV by direct effects on macrophages or endothelial cells. We used tamoxifen-inducible macrophage-specific or endothelial cell-specific EPOR knockout mice in the laser-induced CNV model, and cultured choroidal endothelial cells isolated from adult human donors. We found that macrophage-specific knockout of EPOR influenced laser-induced CNV in females only, whereas endothelial-specific knockout of EPOR reduced laser-induced CNV in male mice only. In cultured human choroidal endothelial cells, knockdown of EPOR reduced EPO-induced signal transducer and activator of transcription 3 (STAT3) activation. Taken together, our findings suggest that EPOR signaling in macrophages or choroidal endothelial cells regulates the development of CNV in a sex-dependent manner. Further studies regarding the role of EPO-induced signaling are required to assess EPO safety and to select or develop appropriate therapeutic approaches.
C1 [Ramshekar, Aniket; Bretz, Colin A.; Kunz, Eric; Cung, Thaonhi; Hartnett, M. Elizabeth] Univ Utah, John A Moran Eye Ctr, Dept Ophthalmol & Visual Sci, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
   [Richards, Burt T.; Hageman, Gregory S.] Univ Utah, Sharon Eccles Steele Ctr Translat Med, John A Moran Eye Ctr, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
   [Stoddard, Gregory J.] Univ Utah, Dept Internal Med, 30 N 1900 E, Salt Lake City, UT 84132 USA.
   [Chaqour, Brahim] Univ Penn, Dept Ophthalmol, 422 Curie Blvd, Philadelphia, PA 19104 USA.
C3 Utah System of Higher Education; University of Utah; Utah System of
   Higher Education; University of Utah; Utah System of Higher Education;
   University of Utah; University of Pennsylvania
RP Hartnett, ME (通讯作者)，Univ Utah, John A Moran Eye Ctr, Dept Ophthalmol & Visual Sci, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM u1088294@utah.edu; u6003023@utah.edu; eric.kunz@utah.edu;
   u6036884@utah.edu; burt.richards@hsc.utah.edu;
   greg.stoddard@hsc.utah.edu; gregory.hageman@hsc.utah.edu;
   brahim.chaqour@pennmedicine.upenn.edu; me.hartnett@hsc.utah.edu
RI Chaqour, Brahim/AEH-1314-2022
OI Chaqour, Brahim/0000-0002-8516-4324; Richards, Burt/0000-0003-1789-2335;
   Kunz, Eric/0000-0003-0960-5324
FU National Institutes of Health/National Eye Institute [F30EY032311,
   R01EY015130, R01EY017011, R01EY024998]; Research to Prevent Blindness,
   New York, NY, USA; National Institutes of Health Core Grant
   [P30EY014800]; Steele Center for Translational Medicine
FX This research was funded by the National Institutes of Health/National
   Eye Institute R01EY015130 to M.E.H., the National Institutes of
   Health/National Eye Institute R01EY017011 to M.E.H., the National
   Institutes of Health/National Eye Institute F30EY032311, the National
   Institutes of Health Core Grant P30EY014800, an Unrestricted Grant from
   Research to Prevent Blindness, New York, NY, USA to the Department of
   Ophthalmology & Visual Sciences, University of Utah, and the National
   Institutes of Health/National Eye institute R01EY024998 to B.C.
   Ascertainment and processing of human eyes were supported by funding
   procured by the Steele Center for Translational Medicine to G.S.H.
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NR 46
TC 0
Z9 0
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2227-9059
J9 BIOMEDICINES
JI Biomedicines
PD JUL
PY 2022
VL 10
IS 7
AR 1655
DI 10.3390/biomedicines10071655
PG 15
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental;
   Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Research & Experimental Medicine;
   Pharmacology & Pharmacy
GA 3G9WO
UT WOS:000831696600001
PM 35884958
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Voigt, AP
   Mullin, NK
   Mulfaul, K
   Lozano, LP
   Wiley, LA
   Flamme-Wiese, MJ
   Boese, EA
   Han, IC
   Scheetz, TE
   Stone, EM
   Tucker, BA
   Mullins, RF
AF Voigt, Andrew P.
   Mullin, Nathaniel K.
   Mulfaul, Kelly
   Lozano, Lola P.
   Wiley, Luke A.
   Flamme-Wiese, Miles J.
   Boese, Erin A.
   Han, Ian C.
   Scheetz, Todd E.
   Stone, Edwin M.
   Tucker, Budd A.
   Mullins, Robert F.
TI Choroidal endothelial and macrophage gene expression in atrophic and
   neovascular macular degeneration
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; MATRICELLULAR PROTEIN; BRUCHS
   MEMBRANE; HUMAN EYES; CELLS; SPARC; HEVIN; ADHESION; CD31; DRUSEN
AB The human choroid is a heterogeneous, highly vascular connective tissue that dysfunctions in age-related macular degeneration (AMD). In this study, we performed single-cell RNA sequencing on 21 human choroids, 11 of which were derived from donors with early atrophic or neovascular AMD. Using this large donor cohort, we identified new gene expression signatures and immunohistochemically characterized discrete populations of resident macrophages, monocytes/inflammatory macrophages and dendritic cells. These three immune populations demonstrated unique expression patterns for AMD genetic risk factors, with dendritic cells possessing the highest expression of the neovascular AMD-associated MMP9 gene. Additionally, we performed trajectory analysis to model transcriptomic changes across the choroidal vasculature, and we identified expression signatures for endothelial cells from choroidal arterioles and venules. Finally, we performed differential expression analysis between control, early atrophic AMD, and neovascular AMD samples, and we observed that early atrophic AMD samples had high expression of SPARCL1, a gene that has been shown to increase in response to endothelial damage. Likewise, neovascular endothelial cells harbored gene expression changes consistent with endothelial cell damage and demonstrated increased expression of the sialomucins CD34 and ENCM, which were also observed at the protein level within neovascular membranes. Overall, this study characterizes the molecular features of new populations of choroidal endothelial cells and mononuclear phagocytes in a large cohort of AMD and control human donors.
C1 [Voigt, Andrew P.; Mullin, Nathaniel K.; Mulfaul, Kelly; Lozano, Lola P.; Wiley, Luke A.; Flamme-Wiese, Miles J.; Boese, Erin A.; Han, Ian C.; Scheetz, Todd E.; Stone, Edwin M.; Tucker, Budd A.; Mullins, Robert F.] Univ Iowa, Dept Ophthalmol & Visual Sci, Carver Coll Med, Iowa City, IA 52242 USA.
   [Voigt, Andrew P.; Mullin, Nathaniel K.; Mulfaul, Kelly; Lozano, Lola P.; Wiley, Luke A.; Flamme-Wiese, Miles J.; Boese, Erin A.; Han, Ian C.; Scheetz, Todd E.; Stone, Edwin M.; Tucker, Budd A.; Mullins, Robert F.] Univ Iowa, Inst Vis Res, 375 Newton Rd, Iowa City, IA 52242 USA.
C3 University of Iowa; University of Iowa
RP Mullins, RF (通讯作者)，Univ Iowa, Inst Vis Res, 375 Newton Rd, Iowa City, IA 52242 USA.
EM robert-mullins@uiowa.edu
OI Mullin, Nathaniel/0000-0003-4320-2852; Voigt,
   Andrew/0000-0001-8107-8317; Lozano, Lauren/0000-0002-0492-4759
FU National Institute of Health [EY031923, EY024605, EY025580, EY033308,
   T32GM008629]; Elmer and Sylvia Sramek Charitable Trust; Research to
   Prevent Blindness; Edward N.& Della L. Thome Memorial Foundation
FX National Institute of Health (grant nos EY031923, EY024605, EY025580,
   EY033308 and T32GM008629); the Elmer and Sylvia Sramek Charitable Trust;
   Research to Prevent Blindness and the Edward N.& Della L. Thome Memorial
   Foundation.
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NR 65
TC 2
Z9 2
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 21
PY 2022
VL 31
IS 14
BP 2406
EP 2423
DI 10.1093/hmg/ddac043
EA FEB 2022
PG 18
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 3D2AM
UT WOS:000770416000001
PM 35181781
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Takasumi, M
   Omori, T
   Machida, T
   Ishida, Y
   Hayashi, M
   Suzuki, T
   Homma, Y
   Endo, Y
   Takahashi, M
   Ohira, H
   Fujita, T
   Sekine, H
AF Takasumi, Mika
   Omori, Tomoko
   Machida, Takeshi
   Ishida, Yumi
   Hayashi, Manabu
   Suzuki, Toshiyuki
   Homma, Yoshimi
   Endo, Yuichi
   Takahashi, Minoru
   Ohira, Hiromasa
   Fujita, Teizo
   Sekine, Hideharu
TI A novel complement inhibitor sMAP-FH targeting both the lectin and
   alternative complement pathways
SO FASEB JOURNAL
LA English
DT Article
DE alternative complement pathway; factor H; lectin complement pathway;
   MAp44; small mannose-binding lectin-associated protein
ID MANNOSE-BINDING LECTIN; PATTERN-RECOGNITION MOLECULES; SERINE-PROTEASE
   (MASP)-1; FACTOR-H; REPERFUSION INJURY; ACTIVATION; SYSTEM; IMMUNOLOGY;
   DOMAINS; FUSION
AB Inhibition of the complement activation has emerged as an option for treatment of a range of diseases. Activation of the lectin and alternative pathways (LP and AP, respectively) contribute to the deterioration of conditions in certain diseases such as ischemia-reperfusion injuries and age-related macular degeneration (AMD). In the current study, we generated dual complement inhibitors of the pathways MAp44-FH and sMAP-FH by fusing full-length MAp44 or small mannose-binding lectin-associated protein (sMAP), LP regulators, with the N-terminal five short consensus repeat (SCR) domains of complement factor H (SCR1/5-FH), an AP regulator. The murine forms of both fusion proteins formed a complex with endogenous mannose-binding lectin (MBL) or ficolin A in the circulation when administered in mice intraperitoneally. Multiple complement activation assays revealed that sMAP-FH had significantly higher inhibitory effects on activation of the LP and AP in vivo as well as in vitro compared to MAp44-FH. Human form of sMAP-FH also showed dual inhibitory effects on LP and AP activation in human sera. Our results indicate that the novel fusion protein sMAP-FH inhibits both the LP and AP activation in mice and in human sera, and could be an effective therapeutic agent for diseases in which both the LP and AP activation are significantly involved.
C1 [Takasumi, Mika; Omori, Tomoko; Machida, Takeshi; Ishida, Yumi; Hayashi, Manabu; Endo, Yuichi; Takahashi, Minoru; Sekine, Hideharu] Fukushima Med Univ, Dept Immunol, Sch Med, Fukushima, Japan.
   [Takasumi, Mika; Hayashi, Manabu; Ohira, Hiromasa] Fukushima Med Univ, Dept Gastroenterol, Sch Med, Fukushima, Japan.
   [Suzuki, Toshiyuki; Homma, Yoshimi] Fukushima Med Univ, Dept Biomol Sci, Sch Med, Fukushima, Japan.
   [Fujita, Teizo] Fukushima Prefectural Gen Hyg Inst, Fukushima, Japan.
C3 Fukushima Medical University; Fukushima Medical University; Fukushima
   Medical University
RP Machida, T (通讯作者)，Fukushima Med Univ, Dept Immunol, 1 Hikarigaoka, Fukushima, Fukushima 9601295, Japan.
EM be204093@fmu.ac.jp
FU Japan Agency for Medical Research and Development (AMED)
   [JP17lm0203002]; MEXT | Japan Society for the Promotion of Science
   (JSPS) [26670478, 19K17440]
FX Curadim Pharma Co., Ltd.; Japan Agency for Medical Research and
   Development (AMED), Grant/Award Number: JP17lm0203002; MEXT | Japan
   Society for the Promotion of Science (JSPS), Grant/Award Number:
   26670478 and 19K17440
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NR 41
TC 2
Z9 2
U1 0
U2 2
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 6598
EP 6612
DI 10.1096/fj.201902475R
EA MAR 2020
PG 15
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:000522483300001
PM 32219899
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Raveendran, M
   Valarmathi, R
AF Raveendran, M.
   Valarmathi, R.
TI Molecular tagging of a novel genetic locus linked to accumulation of
   lutein - A therapeutic carotenoid in rice grains
SO INDIAN JOURNAL OF GENETICS AND PLANT BREEDING
LA English
DT Article
DE Kavuni; lutein; carotenoid; BSA; QTL
ID BULKED SEGREGANT ANALYSIS; MACULAR DEGENERATION; EYE DISEASE; QTL;
   RESISTANCE; ZEAXANTHIN; IDENTIFICATION; BIOSYNTHESIS; TOLERANCE;
   CULTIVAR
AB Lutein is one of the major carotenoids in eye macula and its deficiency is attributed to age-related macular degeneration (AMD) and cataracts. Developing Lutein rich staple food crop will help in supplementing its requirement among rural people through regular diet. The present study was undertaken with a view to tag genetic loci controlling lutein accumulation in rice through Bulked Segregant Analysis (BSA). Estimation of lutein content in the dehusked grains of selected 65 RILs revealed the normal distribution (1.14-285.62 mu g/100gm) of lutein accumulation with a significance of p<0.041. Parental polymorphism survey using > 350 genome wide SSR markers detected 30.8% (108 SSR markers) polymorphism between Kavuni and CO 50 rice genotypes. BSA of extreme bulks containing contrasting levels of lutein along with the parents using the genome wide polymorphic SSR markers resulted in the identification of four SSR markers namely RM197 (3.0 Mb), RM204 (3.1 Mb), RM225 (3.4 Mb) and RM19442 (3.7Mb) on chromosome 6 showing clear association with the lutein content. Single-marker linear regression approach using the allelic pattern of all four markers in the region 3.0-3.7Mb showed significant association with lutein content. The regression analysis showed that the SSR markers in the region 3.0-3.7Mb linked QTL accounted for 35.9% of the genetic variation for lutein content.
C1 [Raveendran, M.; Valarmathi, R.] Tamil Nadu Agr Univ, Ctr Plant Mol Biol & Biotechnol, Dept Plant Biotechnol, Coimbatore 641003, Tamil Nadu, India.
C3 Tamil Nadu Agricultural University
RP Valarmathi, R (通讯作者)，Tamil Nadu Agr Univ, Ctr Plant Mol Biol & Biotechnol, Dept Plant Biotechnol, Coimbatore 641003, Tamil Nadu, India.
EM valarmathimssrf@gmail.com
OI Muthurajan, Raveendran/0000-0002-8803-7662
FU Department of Biotechnology, Government of India
FX The authors thank Department of Biotechnology, Government of India for
   the BioCARe Women scientist fellowship to the corresponding author.
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NR 40
TC 3
Z9 3
U1 0
U2 0
PU INDIAN SOC GENET PLANT BREEDING
PI NEW DELHI
PA PO BOX 11312, INDIAN AGRICULTURE RES INST, NEW DELHI 110012, INDIA
SN 0019-5200
EI 0975-6906
J9 INDIAN J GENET PL BR
JI Indian J. Genet. Plant Breed.
PD FEB
PY 2020
VL 80
IS 1
BP 9
EP 15
DI 10.31742/IJGPB.80.1.2
PG 7
WC Plant Sciences; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Plant Sciences; Genetics & Heredity
GA RN0VT
UT WOS:000640073900003
DA 2022-11-30
ER

PT J
AU Zhao, S
   Lu, L
   Liu, Q
   Chen, J
   Yuan, Q
   Qiu, SM
   Wang, X
AF Zhao, Su
   Lu, Lu
   Liu, Qing
   Chen, Jun
   Yuan, Qi
   Qiu, Shunmei
   Wang, Xian
TI MiR-505 promotes M2 polarization in choroidal neovascularization model
   mice by targeting transmembrane protein 229B
SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE age-related macular degeneration; macrophage polarization; miR-505;
   TMEM229B
ID MACULAR DEGENERATION; ASSOCIATION; MACROPHAGES; MECHANISMS; EXPRESSION;
   CANCER; RISK
AB We aimed to analyse the relative abundance of miR-505 in age-related macular degeneration (AMD) and elucidate its underlying mechanisms. Relative expression of miR-505 was analysed by real-time polymerase chain reaction (PCR). Macrophage polarization was characterized by measurement of molecular markers including Ym-1, Arg-1, TNF-alpha and iNOS via both real-time PCR and Western blot. Vascular endothelial growth factor (VEGF) content was determined by enzyme-linked immunosorbent assay. Choroidal neovascularization (CNV) formation was evaluated by choroidal flat mount technique. The regulatory action of miR-505-5p on 3 ' UTR of Transmembrane Protein 229B (TMEM229B) was interrogated by luciferase reporter assay. miR-505 was aberrantly upregulated in both AMD and laser-induced choroidal neovascularization mouse model. Administration with miR-505 specific inhibitor suppressed M2 polarization in CNV mice as indicated by decreasing both Ym-1 and Arg-1. Meanwhile, VEGF expression and CNV formation were greatly suppressed by miR-505 inhibition as well. The similar phenotype was consolidated in Prostaglandin E2 (PGE2)-stimulated bone marrow-derived macrophages. At the molecular level, miR-505-5p directly targeted and negatively regulated TMEM229B expression, while forced ectopic expression of TMEM229B significantly rescued miR-505-imposed M2 polarization. Our data have uncovered the critical contribution of miR-505 in AMD, which is predominantly mediated by downregulation of TMEM229B.
C1 [Zhao, Su; Yuan, Qi; Qiu, Shunmei; Wang, Xian] Guizhou Med Univ, Affiliated Hosp, Dept Ophthalmol, 9 Beijing Rd, Guiyang 550002, Guizhou, Peoples R China.
   [Lu, Lu] Shenzhen Eye Hosp, Shenzhen Key Lab Ophthalmol, Shenzhen, Peoples R China.
   [Liu, Qing] Tongren Peoples Hosp, Dept Ophthalmol, Tongren, Peoples R China.
   [Chen, Jun] Peoples Hosp Suiyang Cty, Dept Ophthalmol, Suiyang, Peoples R China.
C3 Guizhou Medical University
RP Wang, X (通讯作者)，Guizhou Med Univ, Affiliated Hosp, Dept Ophthalmol, 9 Beijing Rd, Guiyang 550002, Guizhou, Peoples R China.
EM wangxian830@sina.com
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NR 29
TC 7
Z9 7
U1 3
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-9475
EI 1365-3083
J9 SCAND J IMMUNOL
JI Scand. J. Immunol.
PD DEC
PY 2019
VL 90
IS 6
AR e12832
DI 10.1111/sji.12832
EA OCT 2019
PG 11
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA JR2VR
UT WOS:000491210400001
PM 31544253
OA Bronze
DA 2022-11-30
ER

PT J
AU Hussain, RM
   Neiweem, AE
   Kansara, V
   Harris, A
   Ciulla, TA
AF Hussain, Rehan M.
   Neiweem, Ashley E.
   Kansara, Viral
   Harris, Alon
   Ciulla, Thomas A.
TI Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for
   retinal disease
SO EXPERT OPINION ON INVESTIGATIONAL DRUGS
LA English
DT Review
DE Age-related macular degeneration; angiopoietin; AKB-9778; ARP-1536;
   AXT107; diabetic macular edema; faricimab; nesvacumab; Tie-2 receptor;
   vascular endothelial growth factor
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC MACULAR EDEMA; ANGIOPOIETIN-2;
   DEGENERATION; RETINOPATHY; RECEPTOR; VEGF; TIE2; NEOVASCULARIZATION;
   ANGIOGENESIS
AB Introduction: The Tie-2/Angiopoietin pathway is a therapeutic target for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Activation of Tie-2 receptor via Ang-1 maintains vascular stability to limit exudation. Ang-2, a competitive antagonist to Ang-1, and VE-PTP, an endothelial-specific phosphatase, interfere with the Tie-2-Ang-1 axis, resulting in vascular leakage. Areas covered: Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials for nAMD and DME. Nesvacumab is an Ang-2 inhibitor; when coformulated with aflibercept, it failed to show benefit over aflibercept monotherapy in achieving visual gains in phase 2 studies of nAMD and DME. ARP-1536 is an intravitreally administered VE-PTP inhibitor undergoing preclinical studies. AKB-9778 is a subcutaneously administered VE-PTP inhibitor that, when combined with monthly ranibizumab, reduced DME more effectively than ranibizumab monotherapy in a phase 2 study. AKB-9778 monotherapy did not reduce diabetic retinopathy severity score compared to placebo. AXT107, currently in the preclinical phase, promotes conversion of Ang-2 into a Tie-2 agonist and blocks signaling through VEGFR2 and other receptor tyrosine-kinases. Expert opinion: Tie-2/Angiopoietin pathway modulators show promise to reduce treatment burden and improve visual outcomes in nAMD and DME, with potential to treat cases refractory to current treatment modalities.
C1 [Hussain, Rehan M.] Retina Associates, 133 E Brush Hill Rd, Elmhurst, IL 60126 USA.
   [Neiweem, Ashley E.; Harris, Alon; Ciulla, Thomas A.] Indiana Univ Sch Med, Dept Ophthalmol, Indianapolis, IN 46202 USA.
   [Kansara, Viral; Ciulla, Thomas A.] Clearside Biomed Inc, Alpharetta, GA USA.
   [Ciulla, Thomas A.] Midwest Eye Inst, Retina Serv, Indianapolis, IN USA.
C3 Indiana University System; Indiana University Bloomington
RP Hussain, RM (通讯作者)，Retina Associates, 133 E Brush Hill Rd, Elmhurst, IL 60126 USA.
EM Rhussain27@gmail.com
RI Ciulla, Thomas/AAA-1299-2020
OI Ciulla, Thomas/0000-0001-5557-6777
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NR 63
TC 44
Z9 50
U1 2
U2 17
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1354-3784
EI 1744-7658
J9 EXPERT OPIN INV DRUG
JI Expert Opin. Investig. Drugs
PD OCT 3
PY 2019
VL 28
IS 10
BP 861
EP 869
DI 10.1080/13543784.2019.1667333
PG 9
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA JM8LF
UT WOS:000496458900004
PM 31513439
DA 2022-11-30
ER

PT J
AU Stiebing, C
   Schie, IW
   Knorr, F
   Schmitt, M
   Keijzer, N
   Kleemann, R
   Jahn, IJ
   Jahn, M
   Kiliaan, AJ
   Ginner, L
   Lichtenegger, A
   Drexler, W
   Leitgeb, RA
   Popp, J
AF Stiebing, Clara
   Schie, Iwan W.
   Knorr, Florian
   Schmitt, Michael
   Keijzer, Nanda
   Kleemann, Robert
   Jahn, Izabella J.
   Jahn, Martin
   Kiliaan, Amanda J.
   Ginner, Laurin
   Lichtenegger, Antonia
   Drexler, Wolfgang
   Leitgeb, Rainer A.
   Popp, Juergen
TI Nonresonant Raman spectroscopy of isolated human retina samples
   complying with laser safety regulations for in vivo measurements
SO NEUROPHOTONICS
LA English
DT Article
DE Raman imaging; retinal imaging; optical coherence tomography; macular
   pigment; eye safety standard
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR CAROTENOIDS; ADVANCED GLYCATION;
   OCT; ANGIOGRAPHY; PIGMENT
AB Retinal diseases, such as age-related macular degeneration, are leading causes of vision impairment, increasing in incidence worldwide due to an aging society. If diagnosed early, most cases could be prevented. In contrast to standard ophthalmic diagnostic tools, Raman spectroscopy can provide a comprehensive overview of the biochemical composition of the retina in a label-free manner. A proof of concept study of the applicability of nonresonant Raman spectroscopy for retinal investigations is presented. Raman imaging provides valuable insights into the molecular composition of an isolated ex vivo human retina sample by probing the entire molecular fingerprint, i.e., the lipid, protein, carotenoid, and nucleic acid content. The results are compared to morphological information obtained by optical coherence tomography of the sample. The challenges of in vivo Raman studies due to laser safety limitations and predefined optical parameters given by the eye itself are explored. An in-house built setup simulating the optical pathway in the human eye was developed and used to demonstrate that even under laser safety regulations and the above-mentioned optical restrictions, Raman spectra of isolated ex vivo human retinas can be recorded. The results strongly support that in vivo studies using nonresonant Raman spectroscopy are feasible and that these studies provide comprehensive molecular information of the human retina. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.
C1 [Stiebing, Clara; Schie, Iwan W.; Knorr, Florian; Jahn, Izabella J.; Jahn, Martin; Popp, Juergen] Leibniz Inst Photon Technol, Albert Einstein Str, Jena, Germany.
   [Schmitt, Michael; Popp, Juergen] Friedrich Schiller Univ Jena, Inst Phys Chem, Jena, Germany.
   [Schmitt, Michael; Popp, Juergen] Friedrich Schiller Univ Jena, Abbe Ctr Photon, Jena, Germany.
   [Keijzer, Nanda; Kleemann, Robert] Netherlands Org Appl Sci Res, Dept Metab Hlth Res, Leiden, Netherlands.
   [Kiliaan, Amanda J.] Radboud Univ Nijmegen, Preclin Imaging Ctr, Inst Brain Cognit & Behav, Dept Anat Donders,Med Ctr, Nijmegen, Netherlands.
   [Ginner, Laurin; Lichtenegger, Antonia; Drexler, Wolfgang; Leitgeb, Rainer A.] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
   [Jahn, Martin] CiS Forsch Inst Mikrosensor GmbH, Erfurt, Germany.
C3 Leibniz Institut fur Photonische Technologien; Friedrich Schiller
   University of Jena; Friedrich Schiller University of Jena; Netherlands
   Organization Applied Science Research; Radboud University Nijmegen;
   Medical University of Vienna; CiS Forschungsinstitut fur Mikrosensorik
   GmbH
RP Popp, J (通讯作者)，Leibniz Inst Photon Technol, Albert Einstein Str, Jena, Germany.; Popp, J (通讯作者)，Friedrich Schiller Univ Jena, Inst Phys Chem, Jena, Germany.; Popp, J (通讯作者)，Friedrich Schiller Univ Jena, Abbe Ctr Photon, Jena, Germany.
EM juergen.popp@leibnizipht.de
RI Kiliaan, Amanda J/D-8778-2012
OI Ginner, Laurin/0000-0003-1436-2048; Schie, Iwan/0000-0003-0336-3168;
   Drexler, Wolfgang/0000-0002-3557-6398; Jahn,
   Izabella/0000-0002-1186-0925; Leitgeb, Rainer/0000-0002-0131-4111
FU European Union's Horizon 2020 Research and Innovation Program (MOON
   H2020-ICT-2016-1) [732969]
FX The authors acknowledge financial support from the European Union's
   Horizon 2020 Research and Innovation Program (MOON H2020-ICT-2016-1, No.
   732969).
CR [Anonymous], [No title captured]
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NR 40
TC 11
Z9 11
U1 0
U2 4
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 2329-423X
EI 2329-4248
J9 NEUROPHOTONICS
JI Neurophotonics
PD OCT-DEC
PY 2019
VL 6
IS 4
AR 041106
DI 10.1117/1.NPh.6.4.041106
PG 9
WC Neurosciences; Optics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Optics
GA KE5RP
UT WOS:000508613100007
PM 31482104
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Borooah, S
   Stanton, CM
   Marsh, J
   Carss, KJ
   Waseem, N
   Biswas, P
   Agorogiannis, G
   Raymond, L
   Arno, G
   Webster, AR
AF Borooah, Shyamanga
   Stanton, Chloe M.
   Marsh, Joseph
   Carss, Keren J.
   Waseem, Naushin
   Biswas, Pooja
   Agorogiannis, Georgios
   Raymond, Lucy
   Arno, Gavin
   Webster, Andrew R.
TI Whole genome sequencing reveals novel mutations causing autosomal
   dominant inherited macular degeneration
SO OPHTHALMIC GENETICS
LA English
DT Article
DE Macular dystrophy; nyctalopia; whole genome sequencing; C1QTNF5
ID ONSET RETINAL DEGENERATION; PREVALENCE; DEPOSITS; DISEASE; PROTEIN;
   FAMILY; CTRP5; GENE
AB Background: Age-related macular degeneration (AMD) is a common sight threatening condition. However, there are a number of monogenic macular dystrophies that are clinically similar to AMD, which can potentially provide pathogenetic insights. Methods: Three siblings from a non-consanguineous Greek-Cypriot family reported central visual disturbance and nyctalopia. The patients had full ophthalmic examinations and color fundus photography, spectral-domain ocular coherence tomography and scanning laser ophthalmoscopy. Targeted polymerase chain reaction (PCR) was performed as a first step to attempt to identify suspected mutations in C1QTNF5 and TIMP3 followed by whole genome sequencing. Results: The three patients were noted to have symptoms of nyctalopia, early paracentral visual field loss and, in older patients, central vision loss. Imaging identified pseudodrusen, retinal atrophy and RPE-Bruch's membrane separation. Whole genome sequencing of the proband revealed two novel heterozygous variants in C1QTNF5, c.556C>T, and c.569C>G. The mutation segregated with disease in this family, occurred in cis, and resulted in missense amino acid changes P186S and S190W in C1QTNF5. In silico modeling of the variants revealed that the S190W mutations was likely to have the greatest pathologic effect and that the combination of the mutations was likely to have an additive effect. Conclusions: The novel mutations in C1QTNF5 identified here expand the genotypic spectrum of mutations causing late-onset retinal dystrophy.
C1 [Borooah, Shyamanga; Agorogiannis, Georgios; Arno, Gavin; Webster, Andrew R.] Moorfields Eye Hosp, Dept Ophthalmol, London, England.
   [Borooah, Shyamanga] Univ Edinburgh, Ctr Clin Brain Sci, Sch Clin Sci, Edinburgh, Midlothian, Scotland.
   [Borooah, Shyamanga; Biswas, Pooja] Univ Calif San Diego, Shiley Eye Inst, La Jolla, CA 92093 USA.
   [Stanton, Chloe M.; Marsh, Joseph] Univ Edinburgh, Med Res Council Inst Genet & Mol Med, Med Res Council Human Genet Unit, Edinburgh, Midlothian, Scotland.
   [Carss, Keren J.] Univ Cambridge, Dept Hematol, Cambridge, England.
   [Carss, Keren J.; Raymond, Lucy] Cambridge Univ Hosp NHS Fdn Trust, NIHR BioResource Rare Dis, Cambridge Biomed Campus, Cambridge, England.
   [Waseem, Naushin; Arno, Gavin; Webster, Andrew R.] UCL, Inst Ophthalmol, London, England.
   [Raymond, Lucy] Univ Cambridge, Dept Med Genet, Cambridge, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of Edinburgh; University of California
   System; University of California San Diego; University of Edinburgh;
   University of Cambridge; University of Cambridge; University of London;
   University College London; University of Cambridge
RP Borooah, S (通讯作者)，Shiley Eye Inst, 9415 Campus Point Dr, San Diego, CA 92093 USA.
EM shyamanga@aol.com
RI Borooah, Shyamanga/AAM-6581-2021
OI Marsh, Joseph/0000-0003-4132-0628
FU National Institute for Health Research England (NIHR) for the NIHR
   BioResource - Rare Diseases project [RG65966]; Moorfields Eye Hospital,
   UCL Institute of Ophthalmology NIHR Biomedical Research Centre;
   Fulbright-Fight for Sight scholarship; Foundation Fighting Blindness
   Career Development Award; MRC Career Development Award [MR/M02122X/1];
   Fight for Sight senior research fellowship; Medical Research Council
   [MR/M02122X/1]; Programme Grants for Applied Research [RG65966]; MRC
   [MR/M02122X/1] Funding Source: UKRI
FX This work was supported by The National Institute for Health Research
   England (NIHR) for the NIHR BioResource - Rare Diseases project (grant
   number RG65966); The work was also supported by the Moorfields Eye
   Hospital, UCL Institute of Ophthalmology NIHR Biomedical Research
   Centre; Shyamanga Borooah was supported by a Fulbright-Fight for Sight
   scholarship and a Foundation Fighting Blindness Career Development
   Award; Joe Marsh was supported by a MRC Career Development Award
   (MR/M02122X/1); Gavin Arno was sponsored by a Fight for Sight senior
   research fellowship; Medical Research Council [MR/M02122X/1]; Programme
   Grants for Applied Research [RG65966].
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NR 27
TC 9
Z9 9
U1 1
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1381-6810
EI 1744-5094
J9 OPHTHALMIC GENET
JI Ophthalmic Genet.
PD NOV 2
PY 2018
VL 39
IS 6
BP 763
EP 770
DI 10.1080/13816810.2018.1546406
PG 8
WC Genetics & Heredity; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Ophthalmology
GA HC3DP
UT WOS:000451681700015
PM 30451557
OA Green Submitted, Green Accepted
DA 2022-11-30
ER

PT J
AU Sun, YK
   Li, S
   Sun, ZY
AF Sun, Yankui
   Li, Shan
   Sun, Zhongyang
TI Fully automated macular pathology detection in retina optical coherence
   tomography images using sparse coding and dictionary learning
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE optical coherence tomography; age-related macular degeneration; diabetic
   macular edema; sparse coding; max pooling; spatial pyramid matching
ID LAYER SEGMENTATION; OCT IMAGES; THICKNESS; CLASSIFICATION; DEGENERATION;
   TEXTURE
AB We propose a framework for automated detection of dry age-related macular degeneration (AMD) and diabetic macular edema (DME) from retina optical coherence tomography (OCT) images, based on sparse coding and dictionary learning. The study aims to improve the classification performance of state-of-the-art methods. First, our method presents a general approach to automatically align and crop retina regions; then it obtains global representations of images by using sparse coding and a spatial pyramid; finally, a multiclass linear support vector machine classifier is employed for classification. We apply two datasets for validating our algorithm: Duke spectral domain OCT (SD-OCT) dataset, consisting of volumetric scans acquired from 45 subjects-15 normal subjects, 15 AMD patients, and 15 DME patients; and clinical SD-OCT dataset, consisting of 678 OCT retina scans acquired from clinics in Beijing-168, 297, and 213 OCT images for AMD, DME, and normal retinas, respectively. For the former dataset, our classifier correctly identifies 100%, 100%, and 93.33% of the volumes with DME, AMD, and normal subjects, respectively, and thus performs much better than the conventional method; for the latter dataset, our classifier leads to a correct classification rate of 99.67%, 99.67%, and 100.00% for DME, AMD, and normal images, respectively. (C) 2017 Society of Photo-Optical Instrumentation Engineers (SPIE)
C1 [Sun, Yankui; Li, Shan; Sun, Zhongyang] Tsinghua Univ, Dept Comp Sci & Technol, 30 Shuangqing Rd, Beijing 100084, Peoples R China.
   [Li, Shan] Beihang Univ, Sch Software, 37 Xueyuan Rd, Beijing 100191, Peoples R China.
   [Sun, Zhongyang] Sun Yat Sen Univ, Sch Data & Comp Sci, Guangzhou Higher Educ Mega Ctr Univ Town, 132 East Waihuan Rd, Guangzhou 510006, Guangdong, Peoples R China.
C3 Tsinghua University; Beihang University; Sun Yat Sen University
RP Sun, YK (通讯作者)，Tsinghua Univ, Dept Comp Sci & Technol, 30 Shuangqing Rd, Beijing 100084, Peoples R China.
EM syk@mail.tsinghua.edu
RI Sun, Yankui/AAD-2524-2019
FU National Natural Science Foundation of China [61671272]
FX This work was supported by the National Natural Science Foundation of
   China under Grant No. 61671272. We would like to thank the two anonymous
   reviewers for their careful reading of our paper and their many
   insightful comments and suggestions that greatly improved the paper.
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NR 42
TC 47
Z9 48
U1 0
U2 19
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
PY 2017
VL 22
IS 1
AR 016012
DI 10.1117/1.JBO.22.1.016012
PG 11
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 EO0EH
UT WOS:000396370600022
PM 28114453
OA gold
DA 2022-11-30
ER

PT J
AU Camino, A
   Zhang, M
   Dongye, CL
   Pechauer, AD
   Hwang, TS
   Bailey, ST
   Lujan, B
   Wilson, DJ
   Huang, D
   Jia, YL
AF Camino, Acner
   Zhang, Miao
   Dongye, Changlei
   Pechauer, Alex D.
   Hwang, Thomas S.
   Bailey, Steven T.
   Lujan, Brandon
   Wilson, David J.
   Huang, David
   Jia, Yali
TI Automated registration and enhanced processing of clinical optical
   coherence tomography angiography
SO QUANTITATIVE IMAGING IN MEDICINE AND SURGERY
LA English
DT Article
DE Optical coherence tomography angiography (OCTA); motion; artifacts
ID AMPLITUDE-DECORRELATION ANGIOGRAPHY; HUMAN EYE; QUANTIFICATION
AB Background: Motion artifacts degrade the quality of optical coherence tomography angiography (OCTA). Orthogonal registration can eliminate the majority of these artifacts, but some artifacts persist in most clinical images. We evaluate an automated registration algorithm with selective merging and filtering to remove remaining artifacts and improve the quality of images.
   Methods: A 70 kHz commercial spectral domain OCT was used to obtain 3 mm x 3 mm OCTA in 10 healthy, 5 age-related macular degeneration (AMD), and 31 diabetic retinopathy (DR) participants. Projection artifacts were removed and images were segmented into 3 inner retinal plexuses. Amplitude thresholding identified lines containing a residual artifact and correlation between neighboring lines identified distorted stripes. Then the angiograms were registered and the lines selectively merged. A vesselness filter was applied to the resulting images. The images were evaluated for signal-to-noise ratio (SNR), image entropy, vessel connectivity and vessel density.
   Results: Registration and selective merging (RSM) algorithm improved the SNR (P<0.02) compared to orthogonal registration alone. RSM with vesselness filter increased the image entropy (P<10(-8)) and reduced inter-subject variability (standard error <= 3%, n=10) in healthy eyes. The method improved vessel details and connectivity in OCTA of healthy, DR and neovascular AMD eyes.
   Conclusions: This automated registration method eliminates residual motion artifacts and enhances the visualization of vessels in OCTA.
C1 [Camino, Acner; Zhang, Miao; Dongye, Changlei; Pechauer, Alex D.; Hwang, Thomas S.; Bailey, Steven T.; Lujan, Brandon; Wilson, David J.; Huang, David; Jia, Yali] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA.
   [Dongye, Changlei] Shandong Univ Sci & Technol, Coll Informat Sci & Engn, Qingdao 266590, Peoples R China.
C3 Oregon Health & Science University; Shandong University of Science &
   Technology
RP Jia, YL (通讯作者)，Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA.
EM jiaya@ohsu.edu
RI Hwang, Thomas/AAV-5146-2020; Hwang, Thomas S./AAW-6618-2020; dong,
   ye/AEM-5151-2022; Zhang, Miao/F-6574-2017
OI Hwang, Thomas S./0000-0002-0535-4823; Zhang, Miao/0000-0002-3242-5957;
   Bailey, Steven/0000-0003-4949-1464; Jia, Yali/0000-0002-2784-1905
FU National Institutes of Health (Bethesda, MD, USA) [DP3 DK104397, R01
   EY024544, R01 EY023285, P30 EY010572]; Research to Prevent Blindness
   (New York, NY, USA); NATIONAL EYE INSTITUTE [R01EY023285, R01EY024544,
   P30EY010572] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   DIABETES AND DIGESTIVE AND KIDNEY DISEASES [DP3DK104397] Funding Source:
   NIH RePORTER
FX This work was supported by grant DP3 DK104397, R01 EY024544, R01
   EY023285, P30 EY010572 from the National Institutes of Health (Bethesda,
   MD, USA), and by unrestricted departmental funding from Research to
   Prevent Blindness (New York, NY, USA).
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NR 19
TC 28
Z9 28
U1 2
U2 9
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 2223-4292
EI 2223-4306
J9 QUANT IMAG MED SURG
JI Quant. Imaging Med. Surg.
PD AUG
PY 2016
VL 6
IS 4
BP 391
EP 401
DI 10.21037/qims.2016.07.02
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Radiology, Nuclear Medicine & Medical Imaging
GA DX4AW
UT WOS:000384321300007
PM 27709075
OA Green Published
DA 2022-11-30
ER

PT J
AU Ye, Z
   Mayer, J
   Ivacic, L
   Zhou, ZY
   He, M
   Schrodi, SJ
   Page, D
   Brilliant, MH
   Hebbring, SJ
AF Ye, Zhan
   Mayer, John
   Ivacic, Lynn
   Zhou, Zhiyi
   He, Min
   Schrodi, Steven J.
   Page, David
   Brilliant, Murray H.
   Hebbring, Scott J.
TI Phenome-wide association studies (PheWASs) for functional variants
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID ELECTRONIC MEDICAL-RECORDS; ATRIAL-FIBRILLATION; RISK
AB The genome-wide association study (GWAS) is a powerful approach for studying the genetic complexities of human disease. Unfortunately, GWASs often fail to identify clinically significant associations and describing function can be a challenge. GWAS is a phenotype-to-genotype approach. It is now possible to conduct a converse genotype-to-phenotype approach using extensive electronic medical records to define a phenome. This approach associates a single genetic variant with many phenotypes across the phenome and is called a phenome-wide association study (PheWAS). The majority of PheWASs conducted have focused on variants identified previously by GWASs. This approach has been efficient for rediscovering gene-disease associations while also identifying pleiotropic effects for some single-nucleotide polymorphisms (SNPs). However, the use of SNPs identified by GWAS in a PheWAS is limited by the inherent properties of the GWAS SNPs, including weak effect sizes and difficulty when translating discoveries to function. To address these challenges, we conducted a PheWAS on 105 presumed functional stop-gain and stop-loss variants genotyped on 4235 Marshfield Clinic patients. Associations were validated on an additional 10 640 Marshfield Clinic patients. PheWAS results indicate that a nonsense variant in ARMS2 (rs2736911) is associated with age-related macular degeneration (AMD). These results demonstrate that focusing on functional variants may be an effective approach when conducting a PheWAS.
C1 [Ye, Zhan; Mayer, John; He, Min] Marshfield Clin Res Fdn, Biomed Informat Res Ctr, Marshfield, WI 54449 USA.
   [Ivacic, Lynn; He, Min; Schrodi, Steven J.; Brilliant, Murray H.; Hebbring, Scott J.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI 54449 USA.
   [Zhou, Zhiyi] Parkland Hlth & Hosp Syst, Parkland Ctr Clin Innovat, Dallas, TX USA.
   [Page, David; Hebbring, Scott J.] Univ Wisconsin, Computat & Informat Biol & Med, Madison, WI USA.
C3 University of Wisconsin System; University of Wisconsin Madison
RP Hebbring, SJ (通讯作者)，Marshfield Clin Res Fdn, Ctr Human Genet, 1000 N Oak Ave, Marshfield, WI 54449 USA.
EM Hebbring.scott@mcrf.mfldclin.edu
RI Schrodi, Steven J./O-4288-2019
OI Schrodi, Steven J./0000-0003-2304-8528
FU National Center for Research Resources [1UL1RR025011]; National Center
   for Advancing Translational Sciences [9U54TR000021]; U.S. National
   Library of Medicine [5T15LM007359, 1K22LM011938]; Marshfield Clinic
   Research Foundation; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL
   SCIENCES [UL1TR000427] Funding Source: NIH RePORTER; NATIONAL CENTER FOR
   RESEARCH RESOURCES [UL1RR025011] Funding Source: NIH RePORTER; NATIONAL
   LIBRARY OF MEDICINE [T15LM007359, R01LM011028, K22LM011938] Funding
   Source: NIH RePORTER
FX We gratefully acknowledge the support from the National Center for
   Research Resources (1UL1RR025011), National Center for Advancing
   Translational Sciences (9U54TR000021), U.S. National Library of Medicine
   (5T15LM007359 and 1K22LM011938), and the Marshfield Clinic Research
   Foundation. We also thank Rachel Stankowski for her assistance in
   editing this manuscript.
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NR 28
TC 27
Z9 28
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD APR
PY 2015
VL 23
IS 4
BP 523
EP 529
DI 10.1038/ejhg.2014.123
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CD2BI
UT WOS:000350878200017
PM 25074467
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Thorell, MR
   Nunes, RP
   Chen, GW
   Doshi, RR
   Dugar, J
   George, MK
   Kim, BT
   Lowrance, MD
   Modi, D
   Nahas, Z
   Gregori, G
   Yehoshua, Z
   Feuer, W
   Rosenfeld, PJ
AF Thorell, Mariana R.
   Nunes, Renata Portella
   Chen, Gene W.
   Doshi, Rishi R.
   Dugar, Jyoti
   George, Mathew K.
   Kim, Brian T.
   Lowrance, Matthew D.
   Modi, Dimple
   Nahas, Zayna
   Gregori, Giovanni
   Yehoshua, Zohar
   Feuer, William
   Rosenfeld, Philip J.
TI Response to Aflibercept After Frequent Re-treatment With Bevacizumab or
   Ranibizumab in Eyes With Neovascular AMD
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; OPTICAL COHERENCE TOMOGRAPHY; MACULAR
   DEGENERATION; INTRAVITREAL AFLIBERCEPT; RETINA SPECIALISTS; INJECTION;
   OUTCOMES; RESISTANT; THERAPY; TRIAL
AB BACKGROUND AND OBJECTIVE: To evaluate the effects of switching to aflibercept in eyes with neovascular age-related macular degeneration (AMD) requiring frequent re-treatment with bevacizumab or ranibizumab.
   PATIENTS AND METHODS: Retrospective review of 73 eyes of 65 patients with neovascular AMD switched to aflibercept due to persistent or recurrent macular fluid after at least 1 year of intravitreal bevacizumab or ranibizumab with re-treatment at least every 6 weeks. Minimum post-switch follow-up was 6 months. All patients were treated using a treat-and-extend strategy. The treatment intervals immediately after and before the switch were the same.
   RESULTS: The mean pre-switch anti-VEGF therapy duration was 45 months, and the mean number of injections was 31. In the 6 months after the switch, the average number of injections was reduced by 0.6 compared with the 6 months before the switch (P < .001). Visual acuity was unchanged during this period (P = .78). Central retinal thickness (CRT) decreased by 19 mu m after the switch (P < .001). Seventy eyes had vascularized retinal pigment epithelial detachments (PEDs). The decrease in the PED cube-root volume during the 6 months after the switch was statistically significant (-0.07 mm; P = .007).
   CONCLUSION: The number of injections, CRT, and PED volume decreased significantly after the switch to aflibercept, but visual acuity was unchanged.
C1 [Thorell, Mariana R.; Nunes, Renata Portella; Chen, Gene W.; Doshi, Rishi R.; Dugar, Jyoti; George, Mathew K.; Kim, Brian T.; Lowrance, Matthew D.; Modi, Dimple; Nahas, Zayna; Gregori, Giovanni; Yehoshua, Zohar; Feuer, William; Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA.
   [Nunes, Renata Portella] Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil.
C3 Bascom Palmer Eye Institute; University of Miami; Universidade Federal
   de Sao Paulo (UNIFESP)
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 Thorell, Mariana/AAA-9246-2021
FU Carl Zeiss Meditec; Macula Vision Research Foundation; Research to
   Prevent Blindness; NEI [P30 EY014801, R01EY024158]; DOD
   [W81XWH-09-1-0675, W81XWH-13-1-0048 ONOVA]; Feig Family Foundation; Emma
   Clyde Hodge Memorial Foundation; NATIONAL EYE INSTITUTE [R01EY024158]
   Funding Source: NIH RePORTER
FX Supported by a grant from Carl Zeiss Meditec, Macula Vision Research
   Foundation, an unrestricted grant from Research to Prevent Blindness,
   NEI core center grant P30 EY014801 to the University of Miami, NEI grant
   R01EY024158, DOD grants W81XWH-09-1-0675 and W81XWH-13-1-0048 ONOVA,
   Feig Family Foundation, and Emma Clyde Hodge Memorial Foundation.
CR Abedi F, 2014, RETINA-J RET VIT DIS, V34, P1531, DOI 10.1097/IAE.0000000000000134
   Bakall B, 2013, AM J OPHTHALMOL, V156, P15, DOI 10.1016/j.ajo.2013.02.017
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   Yamashita M, 2014, CLIN OPHTHALMOL, V8, P343, DOI 10.2147/OPTH.S56539
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   Yonekawa Y, 2013, CAN J OPHTHALMOL, V48, pE59, DOI 10.1016/j.jcjo.2012.12.015
NR 30
TC 28
Z9 28
U1 0
U2 4
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 NOV-DEC
PY 2014
VL 45
IS 6
BP 526
EP 533
DI 10.3928/23258160-20141118-07
PG 8
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA AY0PQ
UT WOS:000347299300007
PM 25423632
DA 2022-11-30
ER

PT J
AU Nangia, V
   Jonas, JB
   Khare, A
   Bhate, K
   Agarwal, S
   Panda-Jonas, S
AF Nangia, Vinay
   Jonas, Jost B.
   Khare, Anshu
   Bhate, Karishma
   Agarwal, Shubhra
   Panda-Jonas, Songhomitra
TI Prevalence of myelinated retinal nerve fibres in adult Indians: the
   Central India Eye and Medical Study
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE retina; optic nerve; Central India Eye and Medical Study; glaucoma;
   oligodendrocytes; myelinated retinal nerve fibres
AB Abstract.
   Purpose: To determine the prevalence of myelinated retinal nerve fibers in the adult Indian population.
   Methods: The Central India Eye and Medical Study performed in rural Central India included 4711 participants aged 30+ years. The participants underwent a detailed ophthalmic and medical examination.
   Results: Readable fundus photographs were available for 8645 eyes of 4485 (95.2%) subjects. Myelinated retinal nerve fibers were detected in 52 eyes (46 subjects) with a prevalence rate of 0.58 +/- 0.08 per 100 eyes [95% confidence interval (CI): 0.42, 0.74] and 1.03 +/- 0.15 per 100 subjects (95%CI: 0.73, 1.32). Prevalence of myelinated retinal nerve fibers was significantly associated hyperopic refractive error (p = 0.008; OR: 1.31; 95%CI: 1.07, 1.59). It was not significantly associated with age (p = 0.11), best corrected visual acuity (logMAR; p = 0.33), intraocular pressure (p = 0.09), amount of nuclear cataract (p = 0.93), optic disc area (p = 0.60), presence of glaucomatous optic nerve atrophy (p = 0.62), and early age-related macular degeneration (p = 0.53).
   Conclusions: Myelinated retinal nerve fibers are present in about 10 out of 1000 adult Indians in rural Central India, with a higher prevalence in hyperopic eyes. Prevalence of myelinated retinal nerve fibers was not associated with age, visual acuity, glaucoma and macular degeneration.
C1 [Nangia, Vinay; Khare, Anshu; Bhate, Karishma; Agarwal, Shubhra; Panda-Jonas, Songhomitra] Suraj Eye Inst, Nagpur 440004, Maharashtra, India.
   [Jonas, Jost B.] Heidelberg Univ, Dept Ophthalmol, Med Fac Mannheim, D-69115 Heidelberg, Germany.
C3 Suraj Eye Institute; Ruprecht Karls University Heidelberg
RP Nangia, V (通讯作者)，Suraj Eye Inst, Plot 559 New Colony, Nagpur 440004, Maharashtra, India.
EM nagpursuraj@gmail.com
RI Bhate, Karishma/AAD-8609-2019
FU Om Drishti Trust Nagpur; Heidelberg Engineering Co. Heidelberg, Germany;
   Rotary Sight Saver Netherlands; Orbis India; Carl Zeiss Meditec Co.,
   Jena, Germany
FX Supported by an unrestricted grant from Om Drishti Trust Nagpur;
   Heidelberg Engineering Co. Heidelberg, Germany; Rotary Sight Saver
   Netherlands; Orbis India; and Carl Zeiss Meditec Co., Jena, Germany.
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NR 6
TC 5
Z9 6
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD MAY
PY 2014
VL 92
IS 3
BP E235
EP E236
DI 10.1111/aos.12118
PG 2
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AF2HJ
UT WOS:000334532900018
PM 23834732
OA Bronze
DA 2022-11-30
ER

PT J
AU van Zeeburg, EJT
   Cereda, MG
   van Meurs, JC
AF van Zeeburg, Elsbeth J. T.
   Cereda, Matteo G.
   van Meurs, Jan C.
TI Recombinant tissue plasminogen activator, vitrectomy, and gas for recent
   submacular hemorrhage displacement due to retinal macroaneurysm
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Retinal arterial macroaneurysm; Recombinant tissue plasminogen
   activator; Submacular hemorrhage; Gas
ID EXPERIMENTAL SUBRETINAL HEMORRHAGE; PNEUMATIC DISPLACEMENT; ARTERIAL
   MACROANEURYSMS; INTRAVITREAL INJECTION; MACULAR DEGENERATION; ASSISTED
   REMOVAL; MANAGEMENT; RABBITS
AB The visual prognosis of submacular hemorrhages caused by a retinal arterial macroaneurysm (RAM) is poor if left untreated. The use of recombinant tissue plasminogen activator (rtPA) has frequently been reported to displace submacular hemorrhages from the foveal area in patients with age-related macular degeneration. This study aims to investigate the results of displacement of recent-onset submacular hemorrhages due to RAM.
   Institutional retrospective interventional case series of 12 patients with macular hemorrhage due to RAM, who underwent pars plana vitrectomy (PPV); followed in 11 by submacular injection of rtPA and gas tamponade. The main outcome measures were displacement of the hemorrhage, complication rate, and visual acuity at 1 month after surgery and at the last follow-up visit.
   One month after surgery, the hemorrhage had been successfully displaced in ten out of 11 patients. In these ten patients, visual acuity (VA) increased by a mean of 1.2 logMAR at 1 month after surgery. At the last follow-up visit, the mean increase was 1.5 logMAR. Complications consisted of a vitreous hemorrhage and hyphema, retinal detachment, a new submacular hemorrhage, and vitreous hemorrhage after argon laser retinal photocoagulation of the RAM.
   PPV with submacular rtPA and gas injection may successfully displace a recently developed submacular hemorrhage in patients with RAM, with a marked improvement in VA that is likely to be greater than if left untreated.
C1 [van Zeeburg, Elsbeth J. T.] Rotterdam Ophthalm Inst, NL-3011 BH Rotterdam, Netherlands.
   [van Zeeburg, Elsbeth J. T.; Cereda, Matteo G.; van Meurs, Jan C.] Rotterdam Eye Hosp, NL-3000 LM Rotterdam, Netherlands.
   [van Meurs, Jan C.] Univ Med Ctr, Erasmus MC, NL-3000 CA Rotterdam, Netherlands.
C3 Rotterdam Eye Hospital; Erasmus University Rotterdam; Erasmus MC
RP van Zeeburg, EJT (通讯作者)，Rotterdam Ophthalm Inst, Schiedamse Vest 160-D, NL-3011 BH Rotterdam, Netherlands.
EM e.vanzeeburg@oogziekenhuis.nl
FU Rotterdam Eye Hospital Flieringa Research Foundation, Rotterdam, The
   Netherlands; Royal Visio, Rotterdam, The Netherlands
FX 1) The Rotterdam Eye Hospital Flieringa Research Foundation, Rotterdam,
   The Netherlands; 2) Royal Visio, Rotterdam, The Netherlands
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NR 37
TC 10
Z9 10
U1 0
U2 4
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 MAR
PY 2013
VL 251
IS 3
BP 733
EP 740
DI 10.1007/s00417-012-2116-3
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 096PY
UT WOS:000315418000015
PM 22865261
DA 2022-11-30
ER

PT J
AU Fernandez-Robredo, P
   Sadaba, LM
   Salinas-Alaman, A
   Recalde, S
   Rodriguez, JA
   Garcia-Layana, A
AF Fernandez-Robredo, Patricia
   Sadaba, Luis M.
   Salinas-Alaman, Angel
   Recalde, Sergio
   Rodriguez, Jose A.
   Garcia-Layana, Alfredo
TI Effect of Lutein and Antioxidant Supplementation on VEGF Expression,
   MMP-2 Activity, and Ultrastructural Alterations in Apolipoprotein
   E-Deficient Mouse
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; HIGH-FAT DIET; VITAMIN-E; MATRIX
   METALLOPROTEINASES; OXIDATIVE STRESS; NITRIC-OXIDE; MACULAR
   DEGENERATION; BRUCHS MEMBRANE; GROWTH-FACTOR; ANIMAL-MODEL
AB Oxidative stress is involved in the pathogenesis of several diseases such as atherosclerosis and age-related macular degeneration (AMD). ApoE-deficient mice (apoE(-/-)) are a well-established model of genetic hypercholesterolemia and develop retinal alterations similar to those found in humans with AMD. Thus supplementation with lutein or multivitamin plus lutein and glutathione complex (MV) could prevent the onset of these alterations. ApoE(-/-) mice (n = 40, 3 months old) were treated daily for 3 months with lutein (AE-LUT) or MV(two doses): AE-MV15 (15 mg/kg/day) and AE-MV50 (50 mg/kg/day) and were compared to controls with vehicle (AE-C). Wild-type mice (n = 10) were also used as control (WT-C). ApoE(-/-) mice showed higher retinal lipid peroxidation and increased VEGF expression and MMP-2 activity, associated with ultrastructural alterations such as basal laminar deposits, vacuoles, and an increase in Bruch's membrane thickness. While lutein alone partially prevented the alterations observed in apoE(-/-) mice, MV treatment substantially reduced VEGF levels and MMP-2 activity and ameliorated the retinal morphological alterations. These results suggest that oxidative stress in addition to an increased expression and activity of proangiogenic factors could participate in the onset or development of retinal alterations of apoE(-/-) mice. Moreover, these changes could be prevented by efficient antioxidant treatments.
C1 [Fernandez-Robredo, Patricia; Recalde, Sergio; Garcia-Layana, Alfredo] Univ Navarra, Sch Med, Univ Navarra Clin, Expt Ophthalmol Lab, ES-31008 Pamplona, Spain.
   [Sadaba, Luis M.; Salinas-Alaman, Angel; Garcia-Layana, Alfredo] Univ Navarra, Sch Med, Univ Navarra Clin, Dept Ophthalmol, ES-31008 Pamplona, Spain.
   [Rodriguez, Jose A.] Univ Navarra, Ctr Appl Med Res CIMA, Div Cardiovasc Sci, Atherothrombosis Res Lab, ES-31008 Pamplona, Spain.
C3 University of Navarra; University of Navarra; University of Navarra
RP Garcia-Layana, A (通讯作者)，Univ Navarra, Sch Med, Univ Navarra Clin, Expt Ophthalmol Lab, ES-31008 Pamplona, Spain.
EM aglayana@unav.es
RI Recalde, Sergio/D-1815-2017; Rodriguez, Jose/G-7324-2015
OI Recalde, Sergio/0000-0002-9328-9725; Rodriguez, Jose/0000-0002-2094-264X
FU Thea Laboratoires (France); RETICS [RD07/0062]; Departamento de
   Educacion, Gobierno de Navarra; Fundacion Jesus de Gangoiti Barrera
FX The authors are grateful to the staff of the Department of Histology and
   Pathology (Universidad de Navarra), especially Laura Guembe, Ph.D., for
   help with electron microscopy interpretation and to Blanca Irigoyen for
   technical assistance; to the personnel at the Atherosclerosis Research
   Laboratory, Division of Cardiovascular Sciences (CIMA-Universidad de
   Navarra); and to Javier Guillen and Juan Percaz for excellent animal
   care. P. Fernandez-Robredo received a grant from Departamento de
   Educacion, Gobierno de Navarra and from Fundacion Jesus de Gangoiti
   Barrera. Parts of the study were funded by Thea Laboratoires (France)
   and with the structure of RETICS RD07/0062.
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NR 49
TC 16
Z9 19
U1 4
U2 13
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.
PY 2013
VL 2013
AR 213505
DI 10.1155/2013/213505
PG 11
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 144EA
UT WOS:000318921200001
PM 23738034
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Vierkotten, S
   Muether, PS
   Fauser, S
AF Vierkotten, Sarah
   Muether, Philipp S.
   Fauser, Sascha
TI Overexpression of HTRA1 Leads to Ultrastructural Changes in the Elastic
   Layer of Bruch's Membrane via Cleavage of Extracellular Matrix
   Components
SO PLOS ONE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; IN-VIVO;
   METALLOPROTEINASES-3 TIMP-3; TISSUE INHIBITOR; SERINE-PROTEASE; GENE;
   BINDING; DISEASE; FIBULIN-5
AB Variants in the chromosomal region 10q26 are strongly associated with an increased risk for age-related macular degeneration (AMD). Two potential AMD genes are located in this region: ARMS2 and HTRA1 (high-temperature requirement A1). Previous studies have suggested that polymorphisms in the promotor region of HTRA1 result in overexpression of HTRA1 protein. This study investigated the role of HTRA1 overexpression in the pathogenesis of AMD. Transgenic Htra1 mice overexpressing the murine protein in the retinal pigment epithelium (RPE) layer of the retina were generated and characterized by transmission electron microscopy, immunofluorescence staining and Western Blot analysis. The elastic layer of Bruch's membrane (BM) in the Htra1 transgenic mice was fragmented and less continuous than in wild type (WT) controls. Recombinant HTRA1 lacking the N-terminal domain cleaved various extracellular matrix (ECM) proteins. Subsequent Western Blot analysis revealed an overexpression of fibronectin fragments and a reduction of fibulin 5 and tropoelastin in the RPE/choroid layer in transgenic mice compared to WT. Fibulin 5 is essential for elastogenesis by promoting elastic fiber assembly and maturation. Taken together, our data implicate that HTRA1 overexpression leads to an altered elastogenesis in BM through fibulin 5 cleavage. It highlights the importance of ECM related proteins in the development of AMD and links HTRA1 to other AMD risk genes such as fibulin 5, fibulin 6, ARMS2 and TIMP3.
C1 [Vierkotten, Sarah; Muether, Philipp S.; Fauser, Sascha] Univ Cologne, Ctr Ophthalmol, Cologne, Germany.
C3 University of Cologne
RP Vierkotten, S (通讯作者)，Univ Cologne, Ctr Ophthalmol, Cologne, Germany.
EM sfauser@gmx.net
FU Novartis; Retinovit Foundation
FX This work was supported by grants from Novartis and the Retinovit
   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 53
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Z9 112
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 AUG 2
PY 2011
VL 6
IS 8
AR e22959
DI 10.1371/journal.pone.0022959
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 802LF
UT WOS:000293511900018
PM 21829675
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Bharti, K
   Miller, SS
   Arnheiter, H
AF Bharti, Kapil
   Miller, Sheldon S.
   Arnheiter, Heinz
TI The new paradigm: retinal pigment epithelium cells generated from
   embryonic or induced pluripotent stem cells
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Review
DE ES cells; induced pluripotent stem cells; age-related macular
   degeneration; retinitis pigmentosa; cell-based therapy; retinal pigment
   epithelium
ID LIGHT-EVOKED RESPONSES; FACTOR-H POLYMORPHISM; EYE DEVELOPMENT; MACULAR
   DEGENERATION; DIRECTED DIFFERENTIATION; RETINITIS-PIGMENTOSA; CONE
   PHOTORECEPTORS; VISUAL FUNCTION; NEURAL RETINA; MULLER GLIA
AB P>Compared with neural crest-derived melanocytes, retinal pigment epithelium (RPE) cells in the back of the eye are pigment cells of a different kind. They are a part of the brain, form an epithelial monolayer, respond to distinct extracellular signals, and provide functions that far exceed those of a light-absorbing screen. For instance, they control nutrient and metabolite flow to and from the retina, replenish 11-cis-retinal by re-isomerizing all-trans-retinal generated during photoconversion, phagocytose daily a portion of the photoreceptors' outer segments, and secrete cytokines that locally control the innate and adaptive immune systems. Not surprisingly, RPE cell damage is a major cause of human blindness worldwide, with age-related macular degeneration a prevalent example. RPE replacement therapies using RPE cells generated from embryonic or induced pluripotent stem cells provide a novel approach to a rational treatment of such forms of blindness. In fact, RPE-like cells can be obtained relatively easily when stem cells are subjected to a two-step induction protocol, a first step that leads to a neuroectodermal fate and a second to RPE differentiation. Here, we discuss the characteristics of such cells, propose criteria they should fulfill in order to be considered authentic RPE cells, and point out the challenges one faces when using such cells in attempts to restore vision.
C1 [Bharti, Kapil; Arnheiter, Heinz] Natl Inst Neurol Disorders & Stroke, Mammalian Dev Sect, Bethesda, MD USA.
   [Miller, Sheldon S.] NEI, Sect Epithelial & Retinal Physiol & Dis, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of
   Neurological Disorders & Stroke (NINDS); National Institutes of Health
   (NIH) - USA; NIH National Eye Institute (NEI)
RP Bharti, K (通讯作者)，Natl Inst Neurol Disorders & Stroke, Mammalian Dev Sect, Bethesda, MD USA.
EM kapilbharti@ninds.nih.gov
OI Arnheiter, Heinz/0000-0003-2537-1134
FU NIH; NINDS; NEI; NATIONAL EYE INSTITUTE [ZIAEY000510] Funding Source:
   NIH RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
   [ZIANS002790] Funding Source: NIH RePORTER
FX We would like to express our gratitude to Drs Sally Temple, Jeffrey
   Stern, Ronald McKay, Christine Curcio, Monique Dubois-Dalcq and Polly
   Matzinger for invaluable comments on the manuscript, and Vinish Saini
   for help with the artwork in Fig. 1. This work was supported by the
   intramural program of the NIH, NINDS and NEI.
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   Zhang YW, 2010, HUM MOL GENET, V19, P1108, DOI 10.1093/hmg/ddp583
NR 112
TC 93
Z9 103
U1 0
U2 28
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-1471
EI 1755-148X
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD FEB
PY 2011
VL 24
IS 1
BP 21
EP 34
DI 10.1111/j.1755-148X.2010.00772.x
PG 14
WC Oncology; Cell Biology; Dermatology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Cell Biology; Dermatology
GA 706IA
UT WOS:000286210400012
PM 20846177
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Kek, WK
   Miller, J
   Rawson-Lax, E
   Wilson, CG
   Uttamchandani, D
AF Kek, W. K.
   Miller, J.
   Rawson-Lax, E.
   Wilson, C. G.
   Uttamchandani, D.
TI In situ measurement of spectral changes in the anterior eye following
   application of ultraviolet-absorbing compounds
SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
LA English
DT Article
DE Ocular sunscreen; Spectroscopy; Optical fibre; Ocular spectrometer
ID DRUG DETECTION; VISIBLE-LIGHT; RADIATION; TRANSMISSION; DELIVERY;
   CORNEAL; SYSTEM; MEDIA
AB The ocular structures are very sensitive to damage from ultraviolet (UV) radiation, exposure is linked to corneal and conjunctival damage, cataract formation and may also be implicated in the aetiology of age-related macular degeneration. These structures are usually protected by wearing suitable eyeglasses and goggles. An alternative to conventional eyeglasses/goggles is the concept of "liquid sunglasses" which involve the topical application of eye drops that are designed to block harmful UV radiation reaching the sensitive ocular surfaces. The evaluation of such compounds directly applied to the eye surface requires in situ measurements to compare the efficacy of different formulations. A novel ocular spectrometer system has been used to evaluate changes in the transmission of ultraviolet (UV) radiation through the anterior eye following topical application of candidate UV-absorbing formulations. The key feature of the system is the ability to propagate a beam of light tangentially through the anterior eye using a compact, hand-held lens assembly incorporating UV-transmitting optical fibres. A range of formulations containing UV-absorbing compounds were topically applied to ex vivo rabbit eyes. Significant increases in the absorption of the UV spectrum were detected in seven of the eight formulations studied, demonstrating the potential of this measurement technique in the evaluation of formulations developed as potential topical ocular sunscreens. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Miller, J.] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Nedlands, WA 6009, Australia.
   [Kek, W. K.; Rawson-Lax, E.; Wilson, C. G.] Univ Strathclyde, Inst Pharm & Biomed Sci, Glasgow G1 1XW, Lanark, Scotland.
   [Miller, J.; Uttamchandani, D.] Univ Strathclyde, Dept Elect & Elect Engn, Glasgow G1 1XW, Lanark, Scotland.
C3 Lions Eye Institute; University of Western Australia; University of
   Strathclyde; University of Strathclyde
RP Miller, J (通讯作者)，Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, 35 Stirling Highway, Nedlands, WA 6009, Australia.
EM joe@cyllene.uwa.edu.au
RI Uttamchandani, Deepak/D-3163-2012
OI Uttamchandani, Deepak/0000-0002-2362-4874
FU Engineering and Physical Sciences Research Council of the UK; Allergan,
   CA, USA
FX The development of the ocular spectrometer was funded by a grant from
   the Engineering and Physical Sciences Research Council of the UK. The
   evaluation of the ocular sunscreens was funded by a grant from Allergan,
   CA, USA. The authors gratefully acknowledge the advice given by Prof. G.
   Dutton, Department of Paediatric Ophthalmology, Royal Hospital for Sick
   Children, Yorkhill, Glasgow, and Dr. C. Weir, Department of
   Ophthalmology, Gartnavel General Hospital, Glasgow, and the assistance
   of J. Brown and L. Horan of the Biological Procedures Unit, University
   of Strathclyde. We would like to express our gratitude to Professor
   Wallace S. Foulds for his help in the preparation of this paper and for
   his continued support of the project through many years of development
   and application.
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NR 20
TC 3
Z9 3
U1 0
U2 4
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 JUN
PY 2010
VL 75
IS 2
BP 200
EP 205
DI 10.1016/j.ejpb.2010.02.004
PG 6
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 616OB
UT WOS:000279217600016
PM 20144709
DA 2022-11-30
ER

PT J
AU Edussuriya, K
   Sennanayake, S
   Senaratne, T
   Marshall, D
   Sullivan, T
   Selva, D
   Casson, RJ
AF Edussuriya, Kapila
   Sennanayake, Saman
   Senaratne, Tissa
   Marshall, Drew
   Sullivan, Thomas
   Selva, Dinesh
   Casson, Robert J.
TI The Prevalence and Causes of Visual Impairment in Central Sri Lanka The
   Kandy Eye Study
SO OPHTHALMOLOGY
LA English
DT Article
ID CATARACT-SURGERY; LOW-VISION; BLINDNESS; POPULATION; ADULTS; COUNTY;
   CHINA; OLDER
AB Objective: To determine the prevalence and causes of uncorrectable visual impairment in the Kandy District of central Sri Lanka.
   Design: Population-based, cross-sectional study.
   Participants: Inhabitants :40 years of age from villages in the Kandy District were selected by randomized cluster sampling; 1721 eligible participants were identified and 1375 participated in the study.
   Methods: The ophthalmic examination included best-corrected logarithm of the minimum angle of resolution visual acuity (VA), slit-lamp examination of the anterior segment, and dilated stereoscopic fundus examination. The principal cause of visual impairment after best correction was recorded.
   Main Outcome Measures: Visual impairment (better eye <6/18) and blindness (better eye <3/60) after best correction.
   Results: Comprehensive examinations, including VA, were performed on 1375 subjects (79.9% participation rate). The prevalence of blindness was 1.1% (95% confidence interval [CI], 0.002-0.020; 15 participants). The prevalence of visual impairment was 5.9% (95% CI, 0.043-0.075; 81 subjects). Cataract and age-related macular degeneration were the main causes of visual impairment.
   Conclusions: Visual impairment remains a major public health problem in central Sri Lanka. Specific programs directed at reducing the cataract burden need to be implemented.
   Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:52-56 (C) 2009 by the American Academy of Ophthalmology.
C1 [Marshall, Drew; Selva, Dinesh; Casson, Robert J.] Univ Adelaide, S Australian Inst Ophthalmol, Adelaide, SA 5000, Australia.
   [Edussuriya, Kapila; Sennanayake, Saman; Senaratne, Tissa] Gen Hosp, Dept Ophthalmol, Kandy, Sri Lanka.
   [Sullivan, Thomas] Univ Adelaide, Discipline Publ Hlth, Data Management & Anal Ctr, Adelaide, SA 5000, Australia.
C3 University of Adelaide; University of Adelaide
RP Casson, RJ (通讯作者)，Univ Adelaide, S Australian Inst Ophthalmol, Adelaide, SA 5000, Australia.
EM robert.casson@adelaide.edu.au
RI Casson, Robert/D-1561-2013
OI Sullivan, Thomas/0000-0002-6930-5406
FU Pfizer Australia
FX Supported by a grant from Pfizer Australia. This organization had no
   role in the design or conduct of this research.
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NR 19
TC 27
Z9 29
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 JAN
PY 2009
VL 116
IS 1
BP 52
EP 56
DI 10.1016/j.ophtha.2008.08.034
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 392BA
UT WOS:000262276700009
PM 19010549
DA 2022-11-30
ER

PT J
AU Malchiodi-Albedi, F
   Matteucci, A
   Bernardo, A
   Minghetti, L
AF Malchiodi-Albedi, Fiorella
   Matteucci, Andrea
   Bernardo, Antonietta
   Minghetti, Luisa
TI PPAR-gamma, Microglial Cells, and Ocular Inflammation: New Venues for
   Potential Therapeutic Approaches
SO PPAR RESEARCH
LA English
DT Review
ID ACTIVATED-RECEPTOR-GAMMA; ENDOTHELIAL GROWTH-FACTOR; EXPERIMENTAL
   AUTOIMMUNE ENCEPHALOMYELITIS; NECROSIS-FACTOR-ALPHA; EXPERIMENTAL
   ALLERGIC ENCEPHALOMYELITIS; MYELIN OLIGODENDROCYTE GLYCOPROTEIN;
   EPITHELIUM-DERIVED FACTOR; NITRIC-OXIDE PRODUCTION; ANGIOGENESIS
   IN-VITRO; MACULAR DEGENERATION
AB The last decade has witnessed an increasing interest for the role played by the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in controlling inflammation in peripheral organs as well as in the brain. Activation of PPAR-gamma has been shown to control the response of microglial cells, the main macrophage population found in brain parenchyma, and limit the inflammation. The anti-inflammatory capacity of PPAR-gamma agonists has led to the hypothesis that PPAR-gamma might be targeted to modulate degenerative brain diseases in which inflammation has been increasingly recognized as a significant component. Recent experimental evidence suggests that PPAR-gamma agonists could be exploited to treat ocular diseases such as diabetic retinopathy, age-related macular degeneration, autoimmune uveitis, and optic neuritis where inflammation has relevant role. Additional PPAR-gamma agonist beneficial effects could involve amelioration of retinal microcirculation and inhibition of neovascularization. However, PPAR-gamma activation could, in some instances, aggravate the ocular pathology, for example, by increasing the synthesis of vascular endothelial growth factor, a proangiogenic factor that could trigger a vicious circle and further deteriorate retinal perfusion. The development of new in vivo and in vitro models to study ocular inflammation and how to modulate for the eye benefit will be instrumental for the search of effective therapies. Copyright (c) 2008 Fiorella Malchiodi-Albedi et al.
C1 [Malchiodi-Albedi, Fiorella; Bernardo, Antonietta; Minghetti, Luisa] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy.
   [Matteucci, Andrea] GB Bietti Fdn Ophthalmol IRCCS, I-00198 Rome, Italy.
C3 Istituto Superiore di Sanita (ISS); IRCCS - Fondazione "G.B. Bietti" per
   lo Studio e la Ricerca in Oftalmologia
RP Minghetti, L (通讯作者)，Ist Super Sanita, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy.
EM luisa.minghetti@iss.it
RI Antonietta, Bernardo/H-4415-2016; Minghetti, Luisa/I-9540-2014;
   Malchiodi-Albedi, Fiorella/A-5944-2015
OI Antonietta, Bernardo/0000-0002-6590-7530; Minghetti,
   Luisa/0000-0002-7065-4689; Malchiodi-Albedi,
   Fiorella/0000-0001-7202-0391
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NR 154
TC 25
Z9 26
U1 0
U2 1
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1687-4757
EI 1687-4765
J9 PPAR RES
JI PPAR Res.
PY 2008
VL 2008
AR 295784
DI 10.1155/2008/295784
PG 12
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA V13YU
UT WOS:000207702900001
PM 18382616
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Voloboueva, LA
   Killilea, DW
   Atamna, H
   Ames, BN
AF Voloboueva, Ludmila A.
   Killilea, David W.
   Atamna, Hani
   Ames, Bruce N.
TI N-tert-butyl hydroxylamine, a mitochondrial antioxidant, protects human
   retinal pigment epithelial cells from iron overload: relevance to
   macular degeneration
SO FASEB JOURNAL
LA English
DT Article
DE calcitrol; cognition; depression; nutrition; brain development; cytokine
   theory
ID CYTOCHROME-C-OXIDASE; TRANSFERRIN RECEPTOR; OXIDATIVE STRESS; INDUCED
   APOPTOSIS; FERRITIN; GLUTATHIONE; TOXICITY; DAMAGE; CERULOPLASMIN;
   ACCUMULATION
AB Age-related macular degeneration (AMD) is the leading cause of severe visual impairment in the elderly in developed countries. AMD patients have elevated levels of iron within the retinal pigment epithelia (RPE), which may lead to oxidative damage to mitochondria, disruption of retinal metabolism, and vision impairment or loss. As a possible model for iron-induced AMD, we investigated the effects of excess iron in cultured human fetal RPE cells on oxidant levels and mitochondrial cytochrome c oxidase (complex IV) function and tested for protection by N-tert-butyl hydroxylamine (Nt-BHA), a known mitochondrial antioxidant. RPE exposure to ferric ammonium citrate resulted in a time-and dose-dependent increase in intracellular iron, which increased oxidant production and decreased glutathione (GSH) levels and mitochondrial complex IV activity. NtBHA addition to iron-overloaded RPE cells led to a reduction of intracellular iron content, oxidative stress, and partial restoration of complex IV activity and GSH content. NtBHA might be useful in AMD due to its potential to reduce oxidative stress, mitochondrial damage, and age-related iron accumulation, which may damage normal RPE function and lead to loss of vision.-Voloboueva, L. A., Killilea, D. W., Atamna, H., Ames, B. N. N-tert-butyl hydroxylamine, a mitochondrial antioxidant, protects human retinal pigment epithelial cells from iron overload: relevance to macular degeneration.
C1 Childrens Hosp Oakland, Res Inst, Nutr & Metabol Ctr, Oakland, CA 94609 USA.
C3 Children's Hospital Oakland Research Institute; University of California
   System; University of California San Francisco; UCSF Medical Center;
   UCSF Benioff Children's Hospital Oakland
RP Ames, BN (通讯作者)，Childrens Hosp Oakland, Res Inst, Nutr & Metabol Ctr, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA.
EM bames@chori.org
OI Killilea, David/0000-0002-8929-6527
FU NEI NIH HHS [R21 EY016101-01, R21 EY016101-01A1, R01 EY002205-24, R01
   EY002205, R21 EY016101, R21 EY016101-02, R37 EY002205, EY02205] Funding
   Source: Medline; NATIONAL EYE INSTITUTE [R21EY016101, R01EY002205,
   R37EY002205] Funding Source: NIH RePORTER
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NR 71
TC 29
Z9 29
U1 0
U2 10
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 DEC
PY 2007
VL 21
IS 14
BP 4077
EP 4086
DI 10.1096/fj.07-8396com
PG 10
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 236DP
UT WOS:000251283500032
PM 17656467
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Nishijima, K
   Ng, YS
   Zhong, LC
   Bradley, J
   Schubert, W
   Jo, N
   Akita, J
   Samuelsson, SJ
   Robinson, GS
   Adamis, AP
   Shima, DT
AF Nishijima, Kazuaki
   Ng, Yin-Shan
   Zhong, Lichun
   Bradley, John
   Schubert, William
   Jo, Nobuo
   Akita, Jo
   Samuelsson, Steven J.
   Robinson, Gregory S.
   Adamis, Anthony P.
   Shima, David T.
TI Vascular endothelial growth factor-A is a survival factor for retinal
   neurons and a critical neuroprotectant during the adaptive response to
   ischemic injury
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID STIMULATES AXONAL OUTGROWTH; NITRIC-OXIDE; INCREASED EXPRESSION;
   CEREBRAL-ISCHEMIA; CELL-SURVIVAL; VEGF; ERYTHROPOIETIN; DEATH;
   ANGIOGENESIS; PERMEABILITY
AB Vascular endothelial growth factor-A (VEGF-A) has recently been recognized as an important neuroprotectant in the central nervous system. Given its position as an anti-angiogenic target in the treatment of human diseases, understanding the extent of VEGF's role in neural cell survival is paramount. Here, we used a model of ischemia-reperfusion injury and found that VEGF-A exposure resulted in a dose-dependent reduction in retinal neuron apoptosis. Although mechanistic studies suggested that VEGF-A-induced volumetric blood How to the retina may be partially responsible for the neuroprotection, ex vivo retinal culture demonstrated a direct neuroprotective effect for VEGF-A. VEGF receptor-2 (VEGFR2) expression was detected in several neuronal cell layers of the retina, and functional analyses showed that VEGFR2 was involved in retinal neuroprotection. VEGF-A was also shown to be involved in the adaptive response to retinal ischemia. Ischemic preconditioning 24 hours before ischemia-reperfusion injury increased VEGF-A levels and substantially decreased the number of apoptotic retinal cells. The protective effect of ischemic preconditioning was reversed after VEGF-A inhibition. Finally, chronic inhibition of VEGF-A function in normal adult animals led to a significant loss of retinal ganglion cells yet had no observable effect on several vascular parameters. These findings have implications for both neural pathologies and ocular vascular diseases, such as diabetic retinopathy and age-related macular degeneration.
C1 OSI Eyetech Inc, Lexington, MA USA.
RP Shima, DT (通讯作者)，R&D Consultants, 75 Lancaster Ave, Barnet EN4 0ES, Herts, England.
EM davesfenestra@yahoo.com
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NR 50
TC 544
Z9 572
U1 0
U2 25
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUL
PY 2007
VL 171
IS 1
BP 53
EP 67
DI 10.2353/ajpath.2007.061237
PG 15
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 185LO
UT WOS:000247712700008
PM 17591953
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Artunay, O
   Yuzbasioglu, E
   Rasier, R
   Sengul, A
   Bahcecioglu, H
AF Artunay, Ozgur
   Yuzbasioglu, Erdal
   Rasier, Rifat
   Sengul, Alper
   Bahcecioglu, Halil
TI Posterior Reversible Encephalopathy Syndrome After Intravitreal
   Bevacizumab Injection in Patient with Choroidal Neovascular Membrane
   Secondary to Age-Related Maculopathy
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID MACULAR DEGENERATION; AVASTIN
AB The posterior reversible encephalopathy syndrome (PRES), a complex of cerebral disorders including headache, seizures, visual disturbances, is associated with a variety of conditions in which blood pressure rises acutely. Arterial hypertension can occur in systemic administration of bevacizumab. A few cases of systemic injection of bevazicumab-induced PRES have been reported. In this article, we first report on a patient who developed PRES following intravitreal bevazicumab.
C1 [Artunay, Ozgur; Yuzbasioglu, Erdal; Rasier, Rifat; Sengul, Alper; Bahcecioglu, Halil] Istanbul Bilim Univ, Dept Ophthalmol, Istanbul, Turkey.
C3 Demiroglu Bilim University
RP Artunay, O (通讯作者)，Sisli Florence Nightingale Hastanesi, Abide i Hurriyet Sok 1, Istanbul, Turkey.
EM artunay@gmail.com
RI Rasier, Rifat/AHB-8857-2022; Rasier, Rifat/AAK-4259-2021
OI Rasier, Rifat/0000-0003-0963-7991; 
CR Bakri SJ, 2007, OPHTHALMOLOGY, V114, P855, DOI 10.1016/j.ophtha.2007.01.017
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NR 8
TC 12
Z9 12
U1 0
U2 2
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 2010
VL 26
IS 3
BP 301
EP 303
DI 10.1089/jop.2009.0148
PG 3
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 614CW
UT WOS:000279033800014
PM 20565319
DA 2022-11-30
ER

PT J
AU Chingle, R
   Proulx, C
   Lubell, WD
AF Chingle, Ramesh
   Proulx, Caroline
   Lubell, William D.
TI Azapeptide Synthesis Methods for Expanding Side-Chain Diversity for
   Biomedical Applications
SO ACCOUNTS OF CHEMICAL RESEARCH
LA English
DT Review
ID SOLID-PHASE SYNTHESIS; DIPEPTIDE BUILDING-BLOCKS; ALPHA-AZA-ANALOGS;
   BIOLOGICAL-ACTIVITY; PEPTIDE-SYNTHESIS; ORIENTED SYNTHESIS; AMINO-ACIDS;
   DESIGN; INHIBITORS; LIGANDS
AB Mimicry of bioactive conformations is critical for peptide-based, medicinal chemistry because such peptidomimetics may augment stability, enhance affinity, and increase specificity. Azapeptides are peptidomimetics in which the alpha-carbon(s) of one or more amino acid residues are substituted by nitrogen. The resulting semicarbazide analogues have been shown to reinforce beta-turn conformation through the combination of lone pair lone pair repulsion of the adjacent hydrazine nitrogen and urea planarity. Substitution of a semicarbazide for an amino amide residue in a peptide may retain biological activity and add benefits such as improved metabolic stability. The applications of azapeptides include receptor ligands, enzyme inhibitors, prodrugs, probes, and imaging agents. Moreover, azapeptides have proven therapeutic utility. For example, the aza-glycinamide analogue of the luteinizing hormone-releasing hormone analogue Zoladex is a potent long-acting agonist currently used in the clinic for the treatment of prostate and breast cancer. However, the use of azapeptides was hampered by tedious solution-phase synthetic routes for selective hydrazine functionalization. A remarkable stride to overcome this bottleneck was made in 2009 through the introduction of the submonomer procedure for azapeptide synthesis, which enabled addition of diverse side chains onto a common semicarbazone intermediate, providing a means to construct azapeptide libraries by solution and solid-phase chemistry. In brief, aza residues are introduced into the peptide chain using the submonomer strategy by semicarbazone incorporation, deprotonation, N-alkylation, and orthogonal deprotection. Amino acylation of the resulting semicarbazide and elongation gives the desired azapeptide.
   Since the initial report, a number of chemical transformations have taken advantage of the orthogonal chemistry of semicarbazone residues (e.g., Michael additions and N-arylations). In addition, libraries have been synthesized from libraries by diversification of aza-propargylglycine (e.g., A(3) coupling reactions, [1,3]-dipolar cycloadditions, and S-exo-dig cyclizations) and aza-chloroalkylglycine residues. In addition, oxidation of aza-glycine residues has afforded azopeptides that react in pericyclic reactions (e.g., Diels-Alder and Alder-ene chemistry). The bulk of these transformations of aza-glycine residues have been developed by the Lubell laboratory, which has applied such chemistry in the synthesis of ligands with promising biological activity for treating diseases such as cancer and age-related macular degeneration.
   Azapeptide analogues of growth hormone-releasing peptide-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, GHRP-6) have for example been pursued as ligands of the cluster of differentiation 36 receptor (CD36) and show promising activity for the development of treatments for angiogenesis-related diseases, such as age-related macular degeneration, as well as for atherosclerosis. Azapeptides have also been employed to make a series of conformationally constrained second mitochondria-derived activator of caspase (Smac) mirnetics that exhibit promising apoptosis-inducing activity in cancer cells. The synthesis of cyclic azapeptide derivatives was used to make an aza scan to study the conformation activity relationships of the anticancer agent cilengitide, cyclo(RGDf-N(Me)V), and its parent counterpart cyclo(RGDfV), which exhibit potency against human tumor metastasis and tumor-induced angiogenesis. Innovations in the synthesis and application of azapeptides will be presented in this Account, focusing on the creation and use of side-chain diversity in medicinal chemistry.
C1 [Chingle, Ramesh; Proulx, Caroline; Lubell, William D.] Univ Montreal, Dept Chem, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada.
   [Proulx, Caroline] North Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA.
C3 Universite de Montreal; University of North Carolina; North Carolina
   State University
RP Lubell, WD (通讯作者)，Univ Montreal, Dept Chem, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada.
EM william.lubell@umontreal.ca
RI Chingle, Ramesh/AAD-1976-2022
OI Chingle, Ramesh/0000-0003-1175-2454
FU NSERC of Canada; CIHR; Ministere du developpement economique de
   l'innovation et de l'exportation du Quebec [878-2012]; Amorchem; Mperia
   Therapeutics Inc.
FX We thank the NSERC of Canada, the CIHR, the Ministere du developpement
   economique de l'innovation et de l'exportation du Quebec (878-2012),
   Amorchem, and Mperia Therapeutics Inc. for support.
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NR 67
TC 65
Z9 66
U1 3
U2 77
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0001-4842
EI 1520-4898
J9 ACCOUNTS CHEM RES
JI Accounts Chem. Res.
PD JUL
PY 2017
VL 50
IS 7
BP 1541
EP 1556
DI 10.1021/acs.accounts.7b00114
PG 16
WC Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry
GA FB4BC
UT WOS:000406085500006
PM 28598597
DA 2022-11-30
ER

PT J
AU Blinder, K
   Blumenkranz, M
   DeSmet, M
   Fish, G
   Friedlander, M
   Gitter, K
   Godley, B
   Ho, A
   Hudson, H
   Van Kuijk, E
   Lewis, ML
   Rosenfeld, P
   Russell, S
   Sabates, F
   Schachat, A
   Schmidt-Erfurth, U
   Schwartz, S
   Singerman, L
   Soubrane, G
   Yannuzzi, L
   D'Amico, DJ
   Regillo, C
   Mieler, WF
   Schneebaum, C
   Beasley, C
   Slakter, JS
   Ciardella, A
   Goldberg, MF
   Hudson, H
   Jerdan, JA
   Krueger, S
   Luna, S
   Robertson, SM
   Russell, S
   Singerman, L
   Slakter, JS
   Sullivan, EK
   Yannuzzi, L
   Zilliox, P
AF Blinder, K
   Blumenkranz, M
   DeSmet, M
   Fish, G
   Friedlander, M
   Gitter, K
   Godley, B
   Ho, A
   Hudson, H
   Van Kuijk, E
   Lewis, ML
   Rosenfeld, P
   Russell, S
   Sabates, F
   Schachat, A
   Schmidt-Erfurth, U
   Schwartz, S
   Singerman, L
   Soubrane, G
   Yannuzzi, L
   D'Amico, DJ
   Regillo, C
   Mieler, WF
   Schneebaum, C
   Beasley, C
   Slakter, JS
   Ciardella, A
   Goldberg, MF
   Hudson, H
   Jerdan, JA
   Krueger, S
   Luna, S
   Robertson, SM
   Russell, S
   Singerman, L
   Slakter, JS
   Sullivan, EK
   Yannuzzi, L
   Zilliox, P
CA Anecortave Acetate Clinical Study
TI Anecortave acetate as monotherapy for the treatment of subfoveal lesions
   in patients with exudative age-related macular degeneration (AMD) -
   Interim (month 6) analysis of clinical safety and efficacy
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE anecortave acetate; age-related macular degeneration (AMD); choroidal
   neovascularization (CNV); angiogenesis; angiostatic agents
ID NEOVASCULARIZATION; STEROIDS
AB Purpose: To evaluate clinical safety and efficacy of the angiostatic agent anecortave acetate for treatment of subfoveal choroidal neovascularization secondary to AMD.
   Methods: 128 patients were randomized to placebo treatment or one of three anecortave acetate doses. Study medication was administered as a posterior juxtascleral injection onto the posterior scleral surface. Best-corrected logMAR vision was obtained at baseline and follow-up visits. Fluorescein angiograms were evaluated for eligibility before enrollment and posttreatment.
   Results: Six months after a single treatment, visual acuity (mean change from baseline logMAR values) was significantly better (P = 0.003) after anecortave acetate 15 mg than placebo. More patients treated with anecortave acetate 15 mg than placebo maintained vision (88% versus 70%, P = 0.080), especially those with predominantly classic lesions (92% versus 65%, P = 0.021). Anecortave acetate 15 mg inhibited lesion growth significantly better than placebo (P = 0.001). Trends favoring the other doses over placebo were observed for vision preservation and lesion inhibition, but statistical significance was not achieved. The Independent Safety Committee overseeing this study identified no clinically relevant treatment-related changes.
   Conclusion: Anecortave acetate 15 mg is safe and effective for preserving or improving vision and for inhibiting lesion growth in patients with subfoveal AMD.
C1 Barnes Retina Inst, St Louis, MO USA.
   Stanford Univ, Sch Med, Stanford, CA 94305 USA.
   Univ Amsterdam, Acad Ctr, Amsterdam, Netherlands.
   Scripps Inst, La Jolla, CA USA.
   Univ Texas, Med Branch, Galveston, TX 77550 USA.
   Wills Eye Hosp & Res Inst, Philadelphia, PA USA.
   Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   Univ Iowa, Sch Med, Iowa City, IA 52242 USA.
   Wilmer Eye Inst, Baltimore, MD USA.
   Med Univ Lubeck, Hosp Eye, Lubeck, Germany.
   Jules Stein Eye Inst, Los Angeles, CA 90024 USA.
   Univ Paris 12, Ophthalmol Clin, Creteil, France.
C3 Washington University (WUSTL); Stanford University; University of
   Amsterdam; Scripps Research Institute; University of Texas System;
   University of Texas Medical Branch Galveston; Jefferson University;
   Bascom Palmer Eye Institute; University of Iowa; Johns Hopkins
   University; Johns Hopkins Medicine; University of Lubeck; Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC)
RP Slakter, JS (通讯作者)，Vitreous Retina Macula Consultants NY, 519 E 72nd St,Suite 203, New York, NY 10021 USA.
OI Russell, Stephen/0000-0003-3776-1367
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NR 11
TC 69
Z9 74
U1 0
U2 1
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 FEB
PY 2003
VL 23
IS 1
BP 14
EP 23
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 679AH
UT WOS:000182898500003
PM 12652226
DA 2022-11-30
ER

PT J
AU Curcio, CA
AF Curcio, CA
TI Imaging maculopathy in post-mortem human eyes
SO VISION RESEARCH
LA English
DT Article
DE ageing; degeneration; drusen; electron microscopy; fundoscopy;
   histochemistry; maculopathy
ID AGE-RELATED MACULOPATHY; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   BRUCHS MEMBRANE; DRUSEN FORMATION; BASAL DEPOSITS; GRADING SYSTEM;
   PREVALENCE; LOCALIZATION; PRIMATE
AB Age-related maculopathy (ARM) remains a poorly understood degeneration. To discover new pathways using contemporary genomics, proteomics, and immunohistochemistry, validate emerging animal models, and validate new imaging modalities, human tissues obtained from donor eyes will be essential to ARM research for the foreseeable future. Because fundus appearance is the clinical diagnostic lingua franca, laboratory investigators adapted these standards to the distinctive appearance of post-mortem tissues in order to identify and stage ARM in donor eyes. Post-mortem tissues offer unique advantages and limitations relative to premortern tissues for imaging studies. One fellow eye can be used for imaging and the other for correlative laboratory studies, if some degree of disease stage asymmetry between eyes is acceptable. Histological verification is a necessary, albeit challenging, step in validating a grading system. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Univ Alabama Birmingham, Sch Med, Dept Ophthalmol, Birmingham, AL 35294 USA.
C3 University of Alabama System; University of Alabama Birmingham
RP Curcio, CA (通讯作者)，Univ Alabama Birmingham, Sch Med, Dept Ophthalmol, UAB Stn, Birmingham, AL 35294 USA.
EM curcio@uab.edu
FU NEI NIH HHS [1R01EY06109] Funding Source: Medline; NATIONAL EYE
   INSTITUTE [R01EY006109] Funding Source: NIH RePORTER
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NR 50
TC 9
Z9 9
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
EI 1878-5646
J9 VISION RES
JI Vision Res.
PD DEC
PY 2005
VL 45
IS 28
BP 3496
EP 3503
DI 10.1016/j.visres.2005.07.038
PG 8
WC Neurosciences; Ophthalmology; Psychology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology; Psychology
GA 997FN
UT WOS:000234230600007
PM 16171840
OA Bronze
DA 2022-11-30
ER

PT J
AU Dunavoelgyi, R
   Sacu, S
   Eibenberger, K
   Palkovits, S
   Leydolt, C
   Pruente, C
   Schmidt-Erfurth, U
AF Dunavoelgyi, Roman
   Sacu, Stefan
   Eibenberger, Katharina
   Palkovits, Stefan
   Leydolt, Christina
   Pruente, Christian
   Schmidt-Erfurth, Ursula
TI RETREATMENT WITH ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY BASED
   ON CHANGES IN VISUAL ACUITY AFTER INITIAL STABILIZATION OF NEOVASCULAR
   AGE-RELATED MACULAR DEGENERATION 3-Year Follow-up Results
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization;
   intravitreal bevacizumab; long-term maintenance
ID INTRAVITREAL BEVACIZUMAB AVASTIN; SUBFOVEAL CHOROIDAL
   NEOVASCULARIZATION; PHOTODYNAMIC THERAPY; RANIBIZUMAB; VEGF;
   VERTEPORFIN; POPULATION; IMPAIRMENT; BLINDNESS
AB Purpose: To evaluate the 3-year therapeutic benefit of intravitreal bevacizumab in neovascular related macular degeneration (nAMD) in a standard clinical setting involving 3 initial injections and a pro re nata regimen as recommended in the PRONTO study.
   Methods: In this interventional clinical study, 181 eyes of 160 consecutive patients with active neovascular related macular degeneration meeting recommended criteria for inclusion and protocol criteria for anti-vascular endothelial growth factor therapy undergoing intravitreal bevacizumab monotherapy were observed. Data of treatment-naive eyes (Group 1, n = 114) were analyzed separately from eyes that had undergone previous photodynamic therapy plus intravitreal triamcinolone (Group 2, n = 67). Re-treatment criteria were based on clinical outcome following the official European label regimen. After 1 year of continuous service at an academic referral center, follow-up was performed in private practices in collaboration with the referral center. Main outcome parameters were best-corrected visual acuity and central retinal thickness.
   Results: After 3 years, best-corrected visual acuity decreased in the overall population (0.23 +/- 0.16 to 0.16 +/- 0.21. P = 0.002) and in both groups compared with baseline (0.24 +/- 0.21 to 0.17 +/- 0.21, Group 1, P = 0.03; 0.22 +/- 0.19 to 0.16 +/- 0.21, Group 2, P > 0.05), whereas central retinal thickness increased in the overall population (291 +/- 92 to 319 +/- 110 mu m, P = 0.01) and in both groups (291 +/- 96 to 325 +/- 117 mu m, Group 1, P > 0.05; 290 +/- 83 to 308 +/- 96 mu m, Group 2, P > 0.05) because of chronic cystic degeneration changes of the macula. Mean treatment rate was 5.1 +/- 3.9 (Group 1) versus 3.7 +/- 2.7 (Group 2, P = 0.01). Five cases of severe intraocular inflammation after intravitreal bevacizumab were documented.
   Discussion: While the functional and morphological benefits persisted for the first year after intravitreal bevacizumab treatment, after this time both functional and morphologic results were disappointing during long-term follow-up with visual acuity loss as the main retreatment criterion. After stabilization of the disease, a monthly follow-up of optical coherence tomography and re-treatment based on morphologic, clinical, and vision outcomes may increase the efficacy in patients with neovascular related macular degeneration under anti-vascular endothelial growth factor treatment. RETINA 32:1471-1479, 2012
C1 [Dunavoelgyi, Roman; Sacu, Stefan; Eibenberger, Katharina; Palkovits, Stefan; Leydolt, Christina; Pruente, Christian; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria.
C3 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.at
OI Dunavoelgyi, Roman/0000-0002-1842-240X; Schmidt-Erfurth,
   Ursula/0000-0002-7788-7311
CR Ambati J, 2003, NAT MED, V9, P1390, DOI 10.1038/nm950
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NR 32
TC 5
Z9 6
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 SEP
PY 2012
VL 32
IS 8
BP 1471
EP 1479
DI 10.1097/IAE.0b013e318236e805
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 004HN
UT WOS:000308672300006
PM 22414958
DA 2022-11-30
ER

PT J
AU Mones, J
   Singh, RP
   Bandello, F
   Souied, E
   Liu, X
   Gale, R
AF Mones, Jordi
   Singh, Rishi P.
   Bandello, Francesco
   Souied, Eric
   Liu, Xin
   Gale, Richard
TI Undertreatment of Neovascular Age-Related Macular Degeneration after 10
   Years of Anti-Vascular Endothelial Growth Factor Therapy in the Real
   World: The Need for A Change of Mindset
SO OPHTHALMOLOGICA
LA English
DT Review
DE Anti-VEGF; Neovascular age-related macular degeneration; Treatment
   burden; Undertreatment
ID ANTI-VEGF TREATMENT; LONG-TERM OUTCOMES; 2.0 MG RANIBIZUMAB;
   TREAT-AND-EXTEND; VISUAL-ACUITY; INTRAVITREAL RANIBIZUMAB; AFLIBERCEPT;
   REGIMEN; EXPERIENCES; INJECTIONS
AB Purpose: To assess the gap between visual acuity (VA) outcomes with anti-vascular endothelial growth factor (anti-VEGF) therapies in clinical trials and real-world practice, and explore the reasons for this gap. Methods: The literature was searched from January 1, 2013, to June 30, 2018, for studies reporting VA gains and injection frequencies in clinical trials and real-world practice. Results: Clinical trials of anti-VEGF agents and their extension studies demonstrated initial VA gains maintained at 4 years and beyond (up to 7 years) with continuous proactive treatment. Visual outcomes correlated with injection frequency. In real-world practice, patients are usually undertreated, accounting for the VA decline over time. Reasons for undertreatment include the burden of injections and monitoring visits imposed on patients/caregivers. However, another primary reason is the general mindset in the ophthalmological community that sustained benefits with treatment are not possible, leading to poor compliance and creating a vicious circle. Conclusions: Initial VA gains can be maintained with more intensive/proactive approaches. Promising new treatments requiring less frequent injections/monitoring will help in the near future; meanwhile, better results could be achieved by changing the community mindset that contributes to undertreatment.
C1 [Mones, Jordi] Inst Macula, Bldg Off 90,Vilana,12, ES-08022 Barcelona, Spain.
   [Mones, Jordi] Barcelona Macula Fdn, Barcelona, Spain.
   [Singh, Rishi P.] Cleveland Clin, Cole Eye Inst, Ctr Ophthalm Bioinformat, Cleveland, OH 44106 USA.
   [Bandello, Francesco] Univ Vita Salute, Sci Inst San Raffaele, Dept Ophthalmol, Milan, Italy.
   [Souied, Eric] Hop Intercommunal Creteil, Dept Ophthalmol, Creteil, France.
   [Liu, Xin] Novartis Pharma AG, Basel, Switzerland.
   [Gale, Richard] Univ York, York Teaching Hosp NHS Fdn Trust, Dept Ophthalmol, York, N Yorkshire, England.
   [Gale, Richard] Univ York, Dept Hlth Sci, York, N Yorkshire, England.
   [Gale, Richard] York Teaching Hosp, York, N Yorkshire, England.
C3 Cleveland Clinic Foundation; Vita-Salute San Raffaele University; IRCCS
   Ospedale San Raffaele; Universite Paris-Est-Creteil-Val-de-Marne (UPEC);
   CHI Creteil; Novartis; University of York - UK; University of York - UK
RP Mones, J (通讯作者)，Inst Macula, Bldg Off 90,Vilana,12, ES-08022 Barcelona, Spain.; Mones, J (通讯作者)，Barcelona Macula Fdn, Ctr Med Teknon, Bldg Off 90,Vilana,12, ES-08022 Barcelona, Spain.
EM jmones@institutmacula.com
RI mones, jordi/CAJ-2963-2022
OI mones, jordi/0000-0003-3685-2160; bandello,
   francesco/0000-0003-3238-9682
FU Novartis Pharma AG, Switzerland
FX This work was sponsored by Novartis Pharma AG, Switzerland.
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NR 61
TC 37
Z9 37
U1 1
U2 4
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
EI 1423-0267
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PD JAN
PY 2020
VL 243
IS 1
BP 1
EP 8
DI 10.1159/000502747
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KD5MJ
UT WOS:000507909500001
PM 31743912
OA Bronze
DA 2022-11-30
ER

PT J
CA Assoc German Ophthalmologists
   Assoc German Ophthalmologists
   German Soc Ophthalmology
   German Retina Soc
TI Statement and supplementary statement from the BVA, the DOG, and the RG
   on laser treatment of drusen in age-related macular degeneration (AMD)
   August 2017, update October 2018
SO OPHTHALMOLOGE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; PROPHYLACTIC TREATMENT; GRID
   PHOTOCOAGULATION; 810-NANOMETER LASER; RPE; THERAPY; NUMBER;
   AUTOFLUORESCENCE; APPEARANCE; DISEASES
C1 [Assoc German Ophthalmologists; Assoc German Ophthalmologists] Berufsverband Augenarzte Deutschlands eV, Dusseldorf, Germany.
   [German Soc Ophthalmology] Deutsch Ophthalmolog Gesellsch, Munich, Germany.
   [German Retina Soc] Retinolog Gesell eV, Freiburg, Germany.
RP Deutsch Ophthalmol Gesell, Platenstr 1, D-80336 Munich, Germany.
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NR 42
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0941-293X
EI 1433-0423
J9 OPHTHALMOLOGE
JI Ophthalmologe
PD JAN
PY 2020
VL 117
IS SUPPL 1
SU 1
SI SI
BP 1
EP 10
DI 10.1007/s00347-019-0889-z
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KW4JS
UT WOS:000521132800001
PM 30997527
DA 2022-11-30
ER

PT J
AU Verma, S
   Kumar, V
   Azad, S
   Bhayana, AA
   Surve, A
   Kumar, S
   Agarwal, P
   Chawla, R
   Venkatesh, P
AF Verma, Saurabh
   Kumar, Vinod
   Azad, Shorya
   Bhayana, Amber Amar
   Surve, Abhidnya
   Kumar, Suneel
   Agarwal, Pulak
   Chawla, Rohan
   Venkatesh, Pradeep
TI Focal choroidal excavation: review of literature
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE Imaging; Inflammation; Retina; Neovascularisation; Macula
ID OPTICAL COHERENCE TOMOGRAPHY; FEATURES; EYES; VASCULOPATHY; ASSOCIATION;
   DISORDERS; SPECTRUM
AB Focal choroidal excavation (FCE) is defined as an area of concavity in choroid detected on optical coherence tomography. These are mostly present in macular region without evidence of accompanying scleral ectasia or posterior staphyloma. Though initially considered to be congenital, increasing number of cases have been identified in association with other choroidal pathologies such as central serous choroidopathy, choroidal neovascularisation, polypoidal choroidal vasculopathy, choroiditis, choroidal tumours. In this review article, we aim to elaborate on the morphology, pathogenesis and differential diagnosis of FCE and specifically discuss the spectrum of diseases with known association along with the impact of their treatment on FCE
C1 [Verma, Saurabh; Kumar, Vinod; Azad, Shorya; Bhayana, Amber Amar; Surve, Abhidnya; Kumar, Suneel; Agarwal, Pulak; Chawla, Rohan; Venkatesh, Pradeep] AIIMS, Dr Rajendra Prasad Ctr Ophthalm Sci, Ophthalmol, New Delhi, India.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi; Dr. Rajendra
   Prasad Centre for Ophthalmic Sciences
RP Azad, S (通讯作者)，AIIMS, Ophthalmol, New Delhi 110029, India.
EM shoryaazad@hotmail.com
OI Chawla, Rohan/0000-0002-6791-4435; Verma, Saurabh/0000-0002-1477-7975
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NR 52
TC 7
Z9 7
U1 2
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 AUG
PY 2021
VL 105
IS 8
BP 1043
EP 1048
DI 10.1136/bjophthalmol-2020-316992
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA TQ6SQ
UT WOS:000678409900003
PM 32788327
DA 2022-11-30
ER

PT J
AU Xing, Y
   Liang, S
   Zhao, YY
   Yang, S
   Ni, H
   Li, HH
AF Xing, Yan
   Liang, Shan
   Zhao, Yuanyuan
   Yang, Shuo
   Ni, He
   Li, Haihang
TI Protection of Aronia melanocarpa Fruit Extract from
   Sodium-Iodate-Induced Damages in Rat Retina
SO NUTRIENTS
LA English
DT Article
DE age-related macular degeneration (AMD); anthocyanidin; antioxidant
   effect; crystallin proteins; secondary degeneration
ID SECONDARY DEGENERATION; ANTHOCYANINS; CELLS; MECHANISMS; ALPHA
AB Age-related macular degeneration (AMD) is one of the major causes of blindness in elderly populations. However, the dry form of AMD has lack of effective treatments. The fruits of Aronia melanocarpa are rich in anthocyanins. In this study, the protective effects of aronia fruit extract on rat retina were investigated using a NaIO3-induced dry AMD model. Full-field electroretinograms (ERGs) showed that b-wave amplitudes were significantly decreased and the retina structures were disordered in the model. The extract treatment alleviated the injuries. The b-wave amplitudes increased 61.5% in Scotopic 0.01ERG, 122.0% in Photopic 3.0ERG, and 106.8% in Photopic 3.0 flicker; the retina structure disorder was improved with the thickness of outer nuclear layer increasing by 44.1%; and the malonaldehyde level was significantly reduced in extract-treated rat retinas compared to the model. The proteomics analysis showed the expressions of five crystallin proteins, alpha-crystallin A chain, beta-crystallin B2, beta-crystallin A3, alpha-crystallin B chain, and gamma-crystallin S, which protect retina ganglion cells, were increased by 7.38-, 7.74-, 15.30-, 4.86-, and 9.14-fold, respectively, in the extract treatment compared to the control, which was also confirmed by immunoblotting. The results suggest that aronia fruit extract, probably due to its anthocyanins, could protect the rat retina by alleviating oxidative damages and by upregulating the crystallin proteins to protect its nerve system.
C1 [Xing, Yan; Ni, He; Li, Haihang] South China Normal Univ, Sch Life Sci, Guangdong Prov Key Lab Biotechnol Plant Dev, Guangzhou 510631, Peoples R China.
   [Liang, Shan] Chinese Acad Sci, Inst Microbiol, Key Lab Microbial Physiol & Metab Engn, Beijing 100101, Peoples R China.
   [Zhao, Yuanyuan] Natl Ctr Prot Sci PHOENIX Ctr, Beijing Proteome Res Ctr, Inst Life, State Key Lab Prote, Beijing 102206, Peoples R China.
   [Yang, Shuo] Guozhen Hlth Technol Beijing Co Ltd, Beijing 102206, Peoples R China.
C3 South China Normal University; Chinese Academy of Sciences; Institute of
   Microbiology, CAS
RP Li, HH (通讯作者)，South China Normal Univ, Sch Life Sci, Guangdong Prov Key Lab Biotechnol Plant Dev, Guangzhou 510631, Peoples R China.
EM xingyan135@163.com; liangshan223@hotmail.com; yuanyuanzhao0@126.com;
   yang8236405@msn.com; 20131032@m.scnu.edu.cn; li_haihang@yahoo.com
OI Li, Hai-Hang/0000-0002-3868-049X
FU Science and Technology Project of Guangzhou [201904010296]; National Key
   R&D Program of China [2017YFA0505702]; Key Research Program [BWS17J025]
FX This work is supported by the Science and Technology Project of
   Guangzhou (No. 201904010296), the National Key R&D Program of China (No.
   2017YFA0505702), and the Key Research Program (BWS17J025).
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NR 40
TC 0
Z9 0
U1 5
U2 5
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-6643
J9 NUTRIENTS
JI Nutrients
PD DEC
PY 2021
VL 13
IS 12
AR 4411
DI 10.3390/nu13124411
PG 11
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 2I9QP
UT WOS:000815305700001
PM 34959962
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Chang, YY
   Lee, YJ
   Hsu, MY
   Wang, ML
   Tsou, SC
   Chen, CC
   Lin, JA
   Hsiao, YP
   Lin, HW
AF Chang, Yuan-Yen
   Lee, Yi-Ju
   Hsu, Min-Yen
   Wang, Meilin
   Tsou, Shang-Chun
   Chen, Ching-Chung
   Lin, Jer-An
   Hsiao, Yai-Ping
   Lin, Hui-Wen
TI Protective Effect of Quercetin on Sodium Iodate-Induced Retinal
   Apoptosis through the Reactive Oxygen Species-Mediated
   Mitochondrion-Dependent Pathway
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration; sodium iodate; human retinal pigment
   epithelium; quercetin; apoptosis; mitochondrial membrane potential
AB Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO3) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO3-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO3-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO3-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO3-mediated apoptosis.
C1 [Chang, Yuan-Yen; Wang, Meilin] Chung Shan Med Univ, Sch Med, Dept Microbiol & Immunol, Taichung 40201, Taiwan.
   [Chang, Yuan-Yen; Wang, Meilin] Chung Shan Med Univ Hosp, Dept Med Educ, Taichung 40201, Taiwan.
   [Lee, Yi-Ju] Chung Shan Med Univ, Chung Shan Med Univ Hosp, Dept Pathol, Taichung 40201, Taiwan.
   [Hsu, Min-Yen; Hsiao, Yai-Ping] Chung Shan Med Univ Hosp, Dept Ophthalmol, Taichung 40201, Taiwan.
   [Hsu, Min-Yen; Hsiao, Yai-Ping] Chung Shan Med Univ, Sch Med, Taichung 40201, Taiwan.
   [Hsu, Min-Yen] Natl Chung Hsing Univ, Biotechnol Ctr, Taichung 40201, Taiwan.
   [Tsou, Shang-Chun] Chung Shan Med Univ, Dept Biomed Sci, Taichung 40201, Taiwan.
   [Chen, Ching-Chung; Lin, Hui-Wen] Asia Univ, Dept Optometry, Taichung 41354, Taiwan.
   [Lin, Jer-An] Natl Chung Hsing Univ, Grad Inst Food Safety, Taichung 40201, Taiwan.
   [Lin, Hui-Wen] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40402, Taiwan.
C3 Chung Shan Medical University; Chung Shan Medical University; Chung Shan
   Medical University Hospital; Chung Shan Medical University; Chung Shan
   Medical University Hospital; Chung Shan Medical University; Chung Shan
   Medical University Hospital; Chung Shan Medical University; National
   Chung Hsing University; Chung Shan Medical University; Asia University
   Taiwan; National Chung Hsing University; China Medical University
   Taiwan; China Medical University Hospital - Taiwan
RP Lin, HW (通讯作者)，Asia Univ, Dept Optometry, Taichung 41354, Taiwan.; Lin, HW (通讯作者)，China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40402, Taiwan.
EM cyy0709@csmu.edu.tw; jasmine.lyl@gmail.com; my.scott.hsu@gmail.com;
   wml@csmu.edu.tw; eq7bie5d@gmail.com; art@asia.edu.tw; lja@nchu.edu.tw;
   amy1234575@gmail.com; d9138001@asia.edu.tw
RI Hsu, MinYen/AAT-2200-2021; Lin, Jer-An/O-1576-2015
OI Lin, Hui-Wen/0000-0002-0738-8509; Lin, Jer-An/0000-0002-1362-1370; Hsu,
   Min-Yen/0000-0002-5488-4257; Chang, Yuan-Yen/0000-0001-6395-4280
FU Ministry of Health andWelfare, Executive Yuan, Taiwan (ROC)
   [CCMP102-RD-004]; Chung Shan Medical University [NCHU-CSMU-10708,
   NCHU-CSMU-10910]; Ministry of Science and Technology, Taiwan
   [MOST-107-2311-B-468-001, MOST-108-2320-B-468-002,
   MOST-110-2636-E-040-001, MOST-109-2320-B-040-004-MY3]
FX The authors would like to thank the Ministry of Health andWelfare,
   Executive Yuan, Taiwan (ROC) (project number: CCMP102-RD-004), Chung
   Shan Medical University (project numbers: NCHU-CSMU-10708 and
   NCHU-CSMU-10910), and the Ministry of Science and Technology, Taiwan
   (project numbers: MOST-107-2311-B-468-001, MOST-108-2320-B-468-002,
   MOST-110-2636-E-040-001 and MOST-109-2320-B-040-004-MY3) for financially
   supporting this research.
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NR 52
TC 7
Z9 8
U1 3
U2 8
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 APR
PY 2021
VL 22
IS 8
AR 4056
DI 10.3390/ijms22084056
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA RT2VT
UT WOS:000644322500001
PM 33919990
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU von der Burchard, C
   Moltmann, M
   Tode, J
   Ehlken, C
   Sudkamp, H
   Theisen-Kunde, D
   Konig, I
   Huttmann, G
   Roider, J
AF von der Burchard, Claus
   Moltmann, Moritz
   Tode, Jan
   Ehlken, Christoph
   Sudkamp, Helge
   Theisen-Kunde, Dirk
   Koenig, Inke
   Huettmann, Gereon
   Roider, Johann
TI Self-examination low-cost full-field OCT (SELFF-OCT) for patients with
   various macular diseases
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration (AMD); Optical coherence tomography
   (OCT); Biomarker; Home monitoring; Macula; Retina
ID TREAT-AND-EXTEND; OPTICAL COHERENCE TOMOGRAPHY; EUROPEAN-SOCIETY;
   RETINAL DISEASES; DEGENERATION; GUIDELINES; MANAGEMENT
AB Purpose The treatment guidelines for many macular diseases rely on frequent monitoring with optical coherence tomography (OCT). However, the burden of frequent disease control leads to low therapy adherence in real life. OCT home monitoring would address this issue but requires an inexpensive and self-operable device. With self-examination low-cost full-field OCT (SELFF-OCT), our group has introduced a novel technology that may fulfill both requirements. In this pilot study, we report the initial experiences with a clinical prototype. Methods Fifty-one patients with different macular diseases were recruited in a cross-sectional study. The most common diseases were age-related macular degeneration (AMD; 39/51), diabetic macular edema (DME; 6/51), and retinal vein occlusion (RVO; 3/51). Patients received a short training in device usage and then performed multiple self-scans with the SELFF-OCT device. For comparison, scans with a standard clinical spectral domain (SD-)OCT were taken. Results After a brief training, 77% of the patients were able to successfully acquire images that were clinically gradable. No significant influence on success could be found for age (p = 0.08) or BCVA (p = 0.97). Relevant disease biomarkers in the most common retinal diseases could be detected. Conclusions SELFF-OCT was used successfully for retinal self-examination and in the future could be used for retinal home monitoring. Future improvements in technology are expected to improve success rates and image quality.
C1 [von der Burchard, Claus; Tode, Jan; Ehlken, Christoph; Roider, Johann] Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller Str 3, D-24105 Kiel, Germany.
   [Moltmann, Moritz; Sudkamp, Helge; Theisen-Kunde, Dirk; Huettmann, Gereon] Med Laser Ctr Lubeck GmbH, Peter Monnik Weg 4, D-23562 Lubeck, Germany.
   [Tode, Jan] Med Sch Hannover, Univ Eye Hosp, Carl Neuberg Str 1, D-30625 Hannover, Germany.
   [Koenig, Inke] Univ Lubeck, Inst Med Biometry & Stat, Ratzeburger Allee 160, D-23562 Lubeck, Germany.
   [Huettmann, Gereon] Univ Lubeck, Inst Biomed Opt, Peter Monnik Weg 4, D-23562 Lubeck, Germany.
C3 University of Kiel; Schleswig Holstein University Hospital; Hannover
   Medical School; University of Lubeck; University of Lubeck
RP von der Burchard, C (通讯作者)，Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller Str 3, D-24105 Kiel, Germany.
EM claus.vonderburchard@uksh.de
RI von der Burchard, Claus/GZG-4104-2022; Hüttmann, Gereon/A-9072-2012;
   König, Inke R/A-4544-2009
OI Hüttmann, Gereon/0000-0002-5051-3037; König, Inke R/0000-0003-0504-6465
FU German Federal Ministry of Education and Research (BMBF) [13 N13766]
FX Open Access funding enabled and organized by Projekt DEAL. This work was
   supported by the German Federal Ministry of Education and Research
   (BMBF) Grant No. 13 N13766.
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NR 27
TC 8
Z9 8
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 JUN
PY 2021
VL 259
IS 6
BP 1503
EP 1511
DI 10.1007/s00417-020-05035-6
EA DEC 2020
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA SK9OI
UT WOS:000600817000001
PM 33346888
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Naaman, E
   Ya'ari, S
   Itzkovich, C
   Safuri, S
   Macsi, F
   Kellerman, L
   Mimouni, M
   Mann, I
   Gazit, E
   Adler-Abramovich, L
   Zayit-Soudry, S
AF Naaman, Efrat
   Ya'ari, Sarah
   Itzkovich, Chen
   Safuri, Shadi
   Macsi, Flora
   Kellerman, Lior
   Mimouni, Michael
   Mann, Irit
   Gazit, Ehud
   Adler-Abramovich, Lihi
   Zayit-Soudry, Shiri
TI The retinal toxicity profile towards assemblies of Amyloid-beta indicate
   the predominant pathophysiological activity of oligomeric species
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; COMPLEMENT ACTIVATION; GENE-EXPRESSION; B-WAVE;
   PROTEIN; DRUSEN; PEPTIDE; NEURODEGENERATION; MECHANISM; DEPOSITS
AB Amyloid-beta (A beta), reported as a significant constituent of drusen, was implicated in the pathophysiology of age-related macular degeneration (AMD), yet the identity of the major pathogenic A beta species in the retina has remained hitherto unclear. Here, we examined the in-vivo retinal impact of distinct supramolecular assemblies of A beta. Fibrillar (A beta 40, A beta 42) and oligomeric (A beta 42) preparations showed clear biophysical hallmarks of amyloid assemblies. Measures of retinal structure and function were studied longitudinally following intravitreal administration of the various A beta assemblies in rats. Electroretinography (ERG) delineated differential retinal neurotoxicity of A beta species. Oligomeric A beta 42 inflicted the major toxic effect, exerting diminished ERG responses through 30 days post injection. A lesser degree of retinal dysfunction was noted following treatment with fibrillar A beta 42, whereas no retinal compromise was recorded in response to A beta 40 fibrils. The toxic effect of A beta 42 architectures was further reflected by retinal glial response. Fluorescence labelling of A beta 42 species was used to detect their accumulation into the retinal tissue. These results provide conceptual evidence of the differential toxicity of particular A beta species in-vivo, and promote the mechanistic understanding of their retinal pathogenicity. Stratifying the impact of pathological A beta aggregation in the retina may merit further investigation to decipher the pathophysiological relevance of processes of molecular self-assembly in retinal disorders.
C1 [Naaman, Efrat; Safuri, Shadi; Macsi, Flora; Mimouni, Michael; Zayit-Soudry, Shiri] Rambam Hlth Care Campus, Dept Ophthalmol, IL-3109601 Haifa, Israel.
   [Ya'ari, Sarah; Adler-Abramovich, Lihi] Tel Aviv Univ, Sackler Fac Med, Goldschleger Sch Dent Med, Dept Oral Biol, IL-69978 Tel Aviv, Israel.
   [Itzkovich, Chen; Safuri, Shadi; Zayit-Soudry, Shiri] Rambam Hlth Care Campus, Clin Res Inst Rambam, IL-3109601 Haifa, Israel.
   [Kellerman, Lior; Mimouni, Michael; Mann, Irit; Zayit-Soudry, Shiri] Technion Israel Inst Technol, Ruth & Bruce Fac Med, Haifa, Israel.
   [Gazit, Ehud] Tel Aviv Univ, Sch Mol Cell Biol & Biotechnol, IL-69978 Tel Aviv, Israel.
C3 Rambam Health Care Campus; Tel Aviv University; Sackler Faculty of
   Medicine; Rambam Health Care Campus; Technion Israel Institute of
   Technology; Tel Aviv University
RP Zayit-Soudry, S (通讯作者)，Rambam Hlth Care Campus, Dept Ophthalmol, IL-3109601 Haifa, Israel.; Adler-Abramovich, L (通讯作者)，Tel Aviv Univ, Sackler Fac Med, Goldschleger Sch Dent Med, Dept Oral Biol, IL-69978 Tel Aviv, Israel.; Zayit-Soudry, S (通讯作者)，Rambam Hlth Care Campus, Clin Res Inst Rambam, IL-3109601 Haifa, Israel.; Zayit-Soudry, S (通讯作者)，Technion Israel Inst Technol, Ruth & Bruce Fac Med, Haifa, Israel.
EM lihia@tauex.tau.ac.il; s_soudry@rambam.health.gov.il
RI Naaman, Efrat/AAC-7760-2021; Gazit, Ehud/M-8026-2019; Mimouni,
   Michael/S-2916-2018; Gazit, Ehud/AHE-9332-2022
OI Gazit, Ehud/0000-0001-5764-1720; Mimouni, Michael/0000-0002-4661-0993; 
FU Israel Science Foundation, Physician-Scientist Grant Program [2346/16]
FX Israel Science Foundation, Physician-Scientist Grant Program 2346/16
   (SZS).
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NR 60
TC 6
Z9 6
U1 0
U2 3
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD DEC 1
PY 2020
VL 10
IS 1
AR 20954
DI 10.1038/s41598-020-77712-9
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA PU0CR
UT WOS:000608976100001
PM 33262378
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Khalid, S
   Akram, MU
   Shehryar, T
   Ahmed, W
   Sadiq, M
   Manzoor, M
   Nosheen, N
AF Khalid, Samina
   Akram, Muhammad Usman
   Shehryar, Tehmina
   Ahmed, Waqas
   Sadiq, Marium
   Manzoor, Mahak
   Nosheen, Nelam
TI Automated diagnosis system forage-relatedmacular degeneration using
   hybrid features set from fundus images
SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY
LA English
DT Article
DE AMD; AFIO; drusen; fundus images; HOG; textural features
ID NEURAL-NETWORKS; DRUSEN; PHOTOGRAPHS
AB Impairment to macula can cause loss of central vision. There are various macular disorders that can affect macular region and if not treated at an early stage can cause irreversible central vision loss. Age-related macular degeneration (AMD) disorder is one of the most threading macular disorder. Bright lesion, drusens presence in macular region is known as the hallmark of AMD disorder. This bright lesion differentiation from other bright lesion like exudates is important for accurate diagnosis of AMD. Focus of this article is automated diagnosis of affected macular region by applying a hybrid features set containing textural, color, and structural/shape features for more accurate detection of AMD at an early stage using fundus images. These features also help to distinguish drusens from exudates. The proposed algorithm at first stage, detect macular region from input fundus image and then perform features extraction based on textural pattern, edge, and structural properties of macular region to classify abnormal macula from normal macula. For classification, we have used support vector machine (SVM), K-nearest neighbor and neural networks but SVM classifier achieves high accuracy. The proposed algorithm is tested on publicly available STARE and locally available AFIO datasets. Attained sensitivity, specificity, and accuracy of our proposed system are 97.5%, 95% and 95.45%, respectively, when applied on STARE dataset. When we have applied our proposed system on AFIO dataset, we have attained sensitivity, specificity, and accuracy of 93.3%, 92% and 92.34%, respectively.
C1 [Khalid, Samina; Sadiq, Marium; Manzoor, Mahak] MUST Univ AJK, Dept Comp Sci & Informat Technol, Mirpur, Azad Kashmir, Pakistan.
   [Akram, Muhammad Usman] Natl Univ Sci & Technol, Coll E&ME, Dept Comp Engn, Rawalpindi, Pakistan.
   [Shehryar, Tehmina] MUST Univ AJK, Dept Software Engn, Mirpur, Azad Kashmir, Pakistan.
   [Ahmed, Waqas] Univ Kotli AJK, Dept Comp Sci & Informat Technol, Kotli, Azad Kashmir, Pakistan.
   [Nosheen, Nelam] Capital Univ Sci & Technol, Dept Comp Sci, Islamabad, Pakistan.
C3 National University of Sciences & Technology - Pakistan; Capital
   University of Science & Technology
RP Khalid, S (通讯作者)，MUST Univ AJK, Dept Comp Sci & Informat Technol, Allama Iqbal Rd, Mirpur, Ajk, Pakistan.
EM samina.csit@must.edu.pk
RI Khalid, Samina/AAV-3527-2021
OI Khalid, Samina/0000-0003-4771-6842
CR Acharya UR, 2017, J COMPUT SCI-NETH, V20, P41, DOI 10.1016/j.jocs.2017.03.005
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NR 45
TC 1
Z9 1
U1 0
U2 3
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-9457
EI 1098-1098
J9 INT J IMAG SYST TECH
JI Int. J. Imaging Syst. Technol.
PD MAR
PY 2021
VL 31
IS 1
BP 236
EP 252
DI 10.1002/ima.22456
EA JUN 2020
PG 17
WC Engineering, Electrical & Electronic; Optics; Imaging Science &
   Photographic Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Optics; Imaging Science & Photographic Technology
GA QC6JM
UT WOS:000543230200001
DA 2022-11-30
ER

PT J
AU Balachandra, A
   Chan, EC
   Paul, JP
   Ng, S
   Chrysostomou, V
   Ngo, S
   Mayadunne, R
   van Wijngaarden, P
AF Balachandra, Asitha
   Chan, Elsa C.
   Paul, Joseph P.
   Ng, Sze
   Chrysostomou, Vicki
   Ngo, Steven
   Mayadunne, Roshan
   van Wijngaarden, Peter
TI A biocompatible reverse thermoresponsive polymer for ocular drug
   delivery
SO DRUG DELIVERY
LA English
DT Article
DE Ocular drug delivery; anti-vascular endothelial growth factor;
   intravitreal injection; reverse thermoresponsive polymer; macular
   degeneration
ID MACULAR DEGENERATION; THERMAL GEL; HYDROGELS; RELEASE; PROTEIN; BURDEN
AB Age-related macular degeneration (AMD) is a leading cause of vision loss, the treatment of which may require monthly intravitreal injections. This is a burden on patients and health services, and new delivery modalities that reduce injection frequency are required. To that end, we investigated the suitability of a novel reverse thermoresponsive polymer (RTP) as an ocular drug-delivery vehicle. In this work, we detail the structure and synthesis of a novel RTP, and determine drug release curves for two drugs commonly used in the treatment of AMD, bevacizumab and aflibercept. Biocompatibility of the RTP was assessed in vitro in human and rat cell lines and in vivo following intravitreal injection in rats. Bevacizumab demonstrated a more appropriate release profile than aflibercept, with 67% released within 14 days and 78% released in total over a 183-day period. No toxic effects of RTP were seen in human or rat cells in up to 14 days of co-culture with RTP. Following intravitreal injection, intraocular pressure was unaffected by the presence of RTP and no changes in retinal function or structure were observed at 1 week or 1 month post-injection. RTP injection did not cause inflammation, gliosis or apoptosis in the retina. This work demonstrates the potential suitability of the novel RTP as a sustained-release vehicle for ocular drug delivery for anti-neovascular therapies. Optimization of polymer chemistry for optimal drug loading and release is needed.
C1 [Balachandra, Asitha; Mayadunne, Roshan] CSIRO Mol Sci & Hlth Technol, Bayview Ave, Clayton, Vic 3169, Australia.
   [Chan, Elsa C.; Paul, Joseph P.; Ng, Sze; Chrysostomou, Vicki; Ngo, Steven; Mayadunne, Roshan; van Wijngaarden, Peter] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Chan, Elsa C.; Paul, Joseph P.; Ng, Sze; Chrysostomou, Vicki; van Wijngaarden, Peter] Univ Melbourne, Dept Surg, Ophthalmol, Melbourne, Vic, Australia.
C3 Commonwealth Scientific & Industrial Research Organisation (CSIRO);
   Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne
RP Mayadunne, R (通讯作者)，CSIRO Mol Sci & Hlth Technol, Bayview Ave, Clayton, Vic 3169, Australia.; van Wijngaarden, P (通讯作者)，Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Peter Howson Wing,Level 7,32 Gisborne St, East Melbourne, Vic 3002, Australia.
EM roshan.mayadunne@gmail.com; peterv@unimelb.edu.au
OI Paul, Joseph/0000-0003-3939-2446
FU CASS Foundation (Science and Medicine Grant); Sylvia and Charles Viertel
   Charitable Foundation [VTL2015CO18]; University of Melbourne Annemarie
   Mankiewicz-Zelkin Fellowship; CSIRO
FX This study was supported by the CASS Foundation (PvW was the recipient
   of a Science and Medicine Grant) and the Sylvia and Charles Viertel
   Charitable Foundation (PvW is the recipient of a Viertel Clinical
   Investigatorship VTL2015CO18). PvW is the recipient of a University of
   Melbourne Annemarie Mankiewicz-Zelkin Fellowship. CERA receives
   Operational Infrastructure Support from the Victorian Government and
   Australian Government NHMRC IRIISS. The polymer synthesis,
   characterization and in-vitro release studies were supported by CSIRO.
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NR 31
TC 9
Z9 9
U1 1
U2 14
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1071-7544
EI 1521-0464
J9 DRUG DELIV
JI Drug Deliv.
PD JAN 1
PY 2019
VL 26
IS 1
BP 343
EP 353
DI 10.1080/10717544.2019.1587042
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA HQ1EL
UT WOS:000462140900001
PM 30905169
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Porwal, P
   Pachade, S
   Kokare, M
   Giancardo, L
   Meriaudeau, F
AF Porwal, Prasanna
   Pachade, Samiksha
   Kokare, Manesh
   Giancardo, Luca
   Meriaudeau, Fabrice
TI Retinal image analysis for disease screening through local tetra
   patterns
SO COMPUTERS IN BIOLOGY AND MEDICINE
LA English
DT Article
DE Retinal image analysis; Diabetic Retinopathy (DR); Age-related Macular
   Degeneration (AMD); Computer Aided Diagnosis (CAD); Local Tetra Patterns
   (LTrP)
ID DIABETIC-RETINOPATHY; TEXTURE CLASSIFICATION; ALGORITHM; FEATURES
AB Age-related Macular Degeneration (AMD) and Diabetic Retinopathy (DR) are the most prevalent diseases responsible for visual impairment in the world. This work investigates discrimination potential in the texture of color fundus images to distinguish between diseased and healthy cases by avoiding the prior lesion segmentation step. It presents a retinal background characterization approach and explores the potential of Local Tetra Patterns (LTrP) for texture classification of AMD, DR and Normal images. Five different experiments distinguishing between DR - normal, AMD - normal, DR - AMD, pathological - normal and AMD - DR - normal cases were conducted and validated using the proposed approach, and promising results were obtained. For all five experiments, different classifiers namely, AdaBoost, c4.5, logistic regression, naive Bayes, neural network, random forest and support vector machine were tested. We experimented with three public datasets, ARIA, STARE and E-Optha. Further, the performance of LTrP is compared with other texture descriptors, such as local phase quantization, local binary pattern and local derivative pattern. In all cases, the proposed method obtained the area under the receiver operating characteristic curve and f - score values higher than 0.78 and 0.746 respectively. It was found that both performance measures achieve over 0.995 for DR and AMD detection using a random forest classifier. The obtained results suggest that the proposed technique can discriminate retinal disease using texture information and has potential to be an important component for an automated screening solution for retinal images.
C1 [Porwal, Prasanna; Pachade, Samiksha; Kokare, Manesh] Shri Guru Gobind Singhji Inst Engn & Technol, Ctr Excellence Signal & Image Proc, Nanded, Maharashtra, India.
   [Porwal, Prasanna; Pachade, Samiksha; Giancardo, Luca] Univ Texas Hlth Sci Ctr Houston, Sch Biomed Informat, Ctr Precis Hlth, Houston, TX 77030 USA.
   [Meriaudeau, Fabrice] Univ Teknol PETRONAS, Dept Elect & Elect Engn, Ctr Intelligent Signal & Imaging Res, Seri Iskandar, Malaysia.
C3 Shri Guru Gobind Singhji Institute of Engineering & Technology;
   University of Texas System; University of Texas Health Science Center
   Houston; Universiti Teknologi Petronas
RP Porwal, P (通讯作者)，Shri Guru Gobind Singhji Inst Engn & Technol, Ctr Excellence Signal & Image Proc, Nanded, Maharashtra, India.
EM porwalprasanna@sggs.ac.in
RI Pachade, Samiksha/L-1119-2019; Kokare, Manesh/AAJ-5588-2020; Giancardo,
   Luca/AGY-0035-2022; Porwal, Prasanna/O-5447-2018
OI Pachade, Samiksha/0000-0001-5226-6706; Giancardo,
   Luca/0000-0002-4862-2277; Porwal, Prasanna/0000-0003-2268-7504
FU World bank through Technical Education Quality Improvement Program
   (TEQIP-II)
FX We would like to thank World bank for supporting our project through
   Technical Education Quality Improvement Program (TEQIP-II) and providing
   state of the art laboratory facilities like Center of Excellence in
   Signal and Image Processing. We thank Dr. Subramanyam Murala, Assistant
   Professor, Indian Institute of Technology Ropar, India for his help in
   the use of LTrP and Dr. Arko Barman, Post-doctoral Researcher, The
   University of Texas Health Science Center at Houston, USA for reviewing
   this paper. We also extend our sincere thanks to the authors of ARIA,
   E-optha and STARE for making their datasets publicly available for the
   research community.
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NR 43
TC 4
Z9 4
U1 1
U2 7
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 NOV 1
PY 2018
VL 102
BP 200
EP 210
DI 10.1016/j.compbiomed.2018.09.028
PG 11
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 HA0IR
UT WOS:000449892200022
PM 30308336
DA 2022-11-30
ER

PT J
AU Mills, JO
   Jalil, A
   Stanga, PE
AF Mills, J. O.
   Jalil, A.
   Stanga, P. E.
TI Electronic retinal implants and artificial vision: journey and present
SO EYE
LA English
DT Review
ID ELECTRICAL-STIMULATION; MORPHOMETRIC-ANALYSIS; SUBRETINAL IMPLANTS;
   VISUAL-PERCEPTION; PROSTHESIS; RESOLUTION; SYSTEM; CORTEX; PERFORMANCE;
   TRIAL
AB Retinitis pigmentosa and age-related macular degeneration are two significant causes of severe visual dysfunction. In both, the retinal photoreceptors degenerate, preventing successful conversion of light into electrical energy that is interpreted in the visual cortex as visual function. Artificial vision or visual function began over two centuries ago with the idea of creating artificial light pulses, or phosphenes, through cortical stimulation. The pursuit is now on to improve artificial visual function. Two retinal implants appear the most likely to succeed in the future having undergone multicentre human trials: the Argus II electronic epiretinal device (Second Sight Medical Products, CA, USA) and Alpha-IMS electronic subretinal device (Retina Implant AG, Germany). The trial results to date are encouraging with visual improvement and acceptable safety profiles reported for both devices. At present, the visual function generated by either device does not offer high enough resolution or acuity for a patient to regain a fully functional life. Despite this, both devices not only have the potential, but have actually improved the vision-related quality of life in a significant number of patients implanted. With this in mind, the economic argument is clear. Provided device-life is long enough, its cost should be acceptable for the obtained improvement in the quality of life. The aim of this Review Article is to assist those readers that may be considering offering any of these devices as a treatment for blindness in Retinitis Pigmentosa.
C1 [Mills, J. O.; Jalil, A.; Stanga, P. E.] Manchester Royal Eye Hosp, Manchester, Lancs, England.
   [Mills, J. O.; Jalil, A.; Stanga, P. E.] Manchester Royal Eye Hosp, Manchester Vis Regenerat MVR Lab, NIHR Wellcome Trust Manchester CRF, Manchester, Lancs, England.
   [Stanga, P. E.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Inst Human Dev, Manchester, Lancs, England.
   [Stanga, P. E.] Univ Manchester, Ctr Ophthalmol & Vis Res, Inst Human Dev, Manchester, Lancs, England.
C3 Manchester Royal Eye Hospital; Manchester Royal Eye Hospital; University
   of Manchester; University of Manchester
RP Stanga, PE (通讯作者)，Manchester Royal Eye Hosp, Ophthalmol & Retinal Regenerat, Oxford Rd, Manchester M13 9WL, Lancs, England.
EM retinaspecialist@btinternet.com
OI Jalil, Assad/0000-0003-3820-137X
FU Second Sight Medical Products Inc.
FX PES: Second Sight Medical Products Inc. (Consultancy, Equipment,
   Research Funding, Lecture Fees, Travel expenses).
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NR 69
TC 62
Z9 62
U1 1
U2 47
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD OCT
PY 2017
VL 31
IS 10
BP 1383
EP 1398
DI 10.1038/eye.2017.65
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FJ5WY
UT WOS:000412825500001
PM 28548648
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Carver, KA
   Lin, CM
   Rickman, CB
   Yang, DL
AF Carver, Kyle A.
   Lin, C. M.
   Rickman, Catherine Bowes
   Yang, Dongli
TI Lack of the P2X(7) receptor protects against AMD-like defects and
   microparticle accumulation in a chronic oxidative stress-induced mouse
   model of AMD
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE P2X(7) receptor; Sodi; AMD; Retinal pigmented epithelium (RPE);
   Oxidative stress; Microparticle (MP)
ID PIGMENT EPITHELIAL-CELLS; P2X7 RECEPTOR; MACULAR DEGENERATION;
   GEOGRAPHIC ATROPHY; RELEASE; ACTIVATION; ATP; DEATH; STIMULATION;
   EXPRESSION
AB The P2X(7) receptor (P2X(7)R) is an ATP-gated ion channel that is a key player in oxidative stress under pathological conditions. The P2X(7)R is expressed in the retinal pigmented epithelium (RPE) and neural retina. Chronic oxidative stress contributes to the pathogenesis of age-related macular degeneration (AMD). Mice lacking Cu, Zn superoxide dismutase (Sod1) developed chronic oxidative stress as well as AMD-like features, but whether the P2X(7)R plays a causative role in oxidative stress-induced AMD is unknown. Thus, the main purpose of this study was to test if concurrent knockout (KO) of P2X(7)R could block AMD-like defects seen in Sod1 KO mice. Using multiple approaches, we demonstrate that Sod1 KO causes AMD-like defects, including positive staining for oxidative stress markers, 3-nitrotyrosine and carboxymethyl lysine, thinning of the RPE and retina, thickening of Bruch's membrane, presence of basal laminar and linear deposits, RPE barrier disruption and accumulation of microglia/macrophages. Moreover, we find that Sod1 KO mice accumulate more microparticles (MPs) within RPE/choroid tissues. Concurrent KO of the P2X(7)R protects against AMD-like defects and MP accumulation in Sod1 KO mice. Together, we show for the first time, that deficiency of P2X7R prevents in vivo oxidative stress-induced accumulation of MPs and AMD-like defects. This work could potentially lead to novel therapies for AMD and other oxidative stress-driven diseases. (C) 2016 The Authors. Published by Elsevier Inc.
C1 [Carver, Kyle A.; Lin, C. M.; Yang, Dongli] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
   [Rickman, Catherine Bowes] Duke Univ, Dept Ophthalmol, Duke Eye Ctr, Durham, NC 27710 USA.
   [Rickman, Catherine Bowes] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA.
C3 University of Michigan System; University of Michigan; Duke University;
   Duke University
RP Yang, DL (通讯作者)，Univ Michigan, Dept Ophthalmol & Visual Sci, Kellogg Eye Ctr, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM dlyang@umich.edu
OI Bowes Rickman, Catherine/0000-0002-8555-9596
FU National Eye Institute (NEI) [P30 EY007003, EY026161]; University of
   Michigan Start-Up Funds; NATIONAL EYE INSTITUTE [P30EY005722,
   P30EY007003, R01EY026161] Funding Source: NIH RePORTER
FX The authors thank Austra Liepa for mouse care, breeding and colony
   management. This work utilized the Core Center for Vision Research
   funded by P30 EY007003 from the National Eye Institute (NEI), and was
   supported by the University of Michigan Start-Up Funds. CBR is supported
   by NEI EY026161.
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NR 32
TC 11
Z9 13
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JAN 1
PY 2017
VL 482
IS 1
BP 81
EP 86
DI 10.1016/j.bbrc.2016.10.140
PG 6
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA EI4KD
UT WOS:000392461600013
PM 27810364
OA Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Sripathi, SR
   He, WL
   Sylvester, O
   Neksumi, M
   Um, JY
   Dluya, T
   Bernstein, PS
   Jahng, WJ
AF Sripathi, Srinivas R.
   He, Weilue
   Sylvester, O'Donnell
   Neksumi, Musa
   Um, Ji-Yeon
   Dluya, Thagriki
   Bernstein, Paul S.
   Jahng, Wan Jin
TI Altered Cytoskeleton as a Mitochondrial Decay Signature in the Retinal
   Pigment Epithelium
SO PROTEIN JOURNAL
LA English
DT Article
DE Prohibitin; Retinal pigment epithelium; Oxidative stress; Protein
   interactome; Mitochondria; Cytoskeleton
ID PROSTATE-CANCER CELLS; VIMENTIN FILAMENTS; IN-VIVO; PROHIBITIN;
   TRAFFICKING; INTERACTOME; APOPTOSIS; TRANSPORT; ORGANELLE; MEMBRANE
AB Mitochondria mediate energy metabolism, apoptosis, and aging, while mitochondrial disruption leads to age-related diseases that include age-related macular degeneration. Descriptions of mitochondrial morphology have been non-systematic and qualitative, due to lack of knowledge on the molecular mechanism of mitochondrial dynamics. The current study analyzed mitochondrial size, shape, and position quantitatively in retinal pigment epithelial cells (RPE) using a systematic computational model to suggest mitochondrial trafficking under oxidative environment. Our previous proteomic study suggested that prohibitin is a mitochondrial decay biomarker in the RPE. The current study examined the prohibitin interactome map using immunoprecipitation data to determine the indirect signaling on cytoskeletal changes and transcriptional regulation by prohibitin. Immunocytochemistry and immunoprecipitation demonstrated that there is a positive correlation between mitochondrial changes and altered filaments as well as prohibitin interactions with kinesin and unknown proteins in the RPE. Specific cytoskeletal and nuclear protein-binding mechanisms may exist to regulate prohibitin-mediated reactions as key elements, including vimentin and p53, to control apoptosis in mitochondria and the nucleus. Prohibitin may regulate mitochondrial trafficking through unknown proteins that include 110 kDa protein with myosin head domain and 88 kDa protein with cadherin repeat domain. Altered cytoskeleton may represent a mitochondrial decay signature in the RPE. The current study suggests that mitochondrial dynamics and cytoskeletal changes are critical for controlling mitochondrial distribution and function. Further, imbalance of retrograde versus anterograde mitochondrial trafficking may initiate the pathogenic reaction in adult-onset neurodegenerative diseases.
C1 [Sripathi, Srinivas R.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21205 USA.
   [He, Weilue] Michigan Technol Univ, Dept Biomed Engn, Houghton, MI 49931 USA.
   [Sylvester, O'Donnell; Jahng, Wan Jin] Amer Univ Nigeria, Dept Petr Chem, Retina Prote Lab, Yola, Nigeria.
   [Neksumi, Musa] Modibbo Adama Univ Technol, Dept Chem, Yola, Nigeria.
   [Um, Ji-Yeon] Seoul Natl Univ Sci & Technol, Dept Optometry, Seoul, South Korea.
   [Dluya, Thagriki] Modibbo Adama Univ Technol, Dept Biochem, Yola, Nigeria.
   [Bernstein, Paul S.] Univ Utah, Sch Med, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Michigan Technological
   University; American University of Nigeria; Seoul National University of
   Science & Technology; Utah System of Higher Education; University of
   Utah
RP Jahng, WJ (通讯作者)，Amer Univ Nigeria, Dept Petr Chem, Retina Prote Lab, Yola, Nigeria.
EM wan.jahng@aun.edu.ng
RI He, Weilue/AAP-1748-2020; Jahng, Wan Jin/C-1236-2018
OI Jahng, Wan Jin/0000-0001-8241-7739
FU Century II Equipment Fund; Michigan Technological University; NSF;
   American University of Nigeria; Research to Prevent Blindness; NATIONAL
   EYE INSTITUTE [R01EY011600] Funding Source: NIH RePORTER
FX We thank Dr. Harold J. Sheedlo (University of North Texas Health Science
   Center) for providing HRP cells. We thank Dr. Cameron Atkinson, Trevor
   Moser, Hyunju Lee, Dr. Hilal Arnouk, Dr. Ruonan Zhang, and Alex Keim for
   their excellent technical assistance. This study was supported by the
   Century II Equipment Fund, Research Excellence Fund from Michigan
   Technological University, Equipment Fund from NSF, Research and Teaching
   assistantship from American University of Nigeria. This work was
   supported in part by an unrestricted grant from Research to Prevent
   Blindness to the University of Utah Department of Ophthalmology and
   Visual Sciences. The authors thank Dr. Tristan Purvis for his critical
   reading and suggestions.
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NR 41
TC 12
Z9 12
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1572-3887
EI 1573-4943
J9 PROTEIN J
JI Protein J.
PD JUN
PY 2016
VL 35
IS 3
BP 179
EP 192
DI 10.1007/s10930-016-9659-9
PG 14
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA DO6TS
UT WOS:000377917000003
PM 27029380
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Mishra, B
   Swaroop, A
   Kandpal, RP
AF Mishra, Bibhudatta
   Swaroop, Anand
   Kandpal, Raj P.
TI Genetic components in diabetic retinopathy
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Diabetic complications; genetic association; multifactorial disease;
   retinal disorders; susceptibility variants
ID ENDOTHELIAL GROWTH-FACTOR; GENOME-WIDE ASSOCIATION; GLYCOSYLATION
   END-PRODUCTS; ALDOSE REDUCTASE-ACTIVITY; FACTOR-H POLYMORPHISM;
   SUSCEPTIBILITY GENES; ALBUMIN EXCRETION; COMPLICATIONS; PREVALENCE;
   INDIA
AB Diabetic retinopathy (DR) is a serious complication of diabetes, which is fast reaching epidemic proportions worldwide. While tight glycemic control remains the standard of care for preventing the progression of DR, better insights into DR etiology require understanding its genetic basis, which in turn may assist in the design of novel treatments. During the last decade, genomic medicine is increasingly being applied to common multifactorial diseases such as diabetes and age-related macular degeneration. The contribution of genetics to the initiation and progression of DR has been recognized for some time, but the involvement of specific genes and genetic variants remains elusive. Several investigations are currently underway for identifying DR susceptibility loci through linkage studies, candidate gene approaches, and genome-wide association studies. Advent of next generation sequencing and high throughput genomic technologies, development of novel bioinformatics tools and collaborations among research teams should facilitate such investigations. Here, we review the current state of genetic studies in DR and discuss reported findings in the context of biochemical, cell biological and therapeutic advances. We propose the development of a consortium in India for genetic studies with large cohorts of patients and controls from limited geographical areas to stratify the impact of the environment. Uniform guidelines should be established for clinical phenotyping and data collection. These studies would permit identification of genetic loci for DR susceptibility in the Indian population and should be valuable for better diagnosis and prognosis, and for clinical management of this blinding disease.
C1 [Mishra, Bibhudatta; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
   [Kandpal, Raj P.] Western Univ Hlth Sci, Dept Basic Med Sci, Pomona, CA USA.
   [Kandpal, Raj P.] Western Univ Hlth Sci, Western Diabet Inst, Pomona, CA USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); Western University of Health Sciences; Western University of
   Health Sciences
RP Swaroop, A (通讯作者)，NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
FU Intramural Research Program of the National Eye Institute [EY000546];
   NATIONAL EYE INSTITUTE [ZIAEY000546] Funding Source: NIH RePORTER
FX Our research is supported by Intramural Research Program of the National
   Eye Institute (EY000546).
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NR 67
TC 15
Z9 15
U1 0
U2 3
PU WOLTERS KLUWER MEDKNOW PUBLICATIONS
PI MUMBAI
PA WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S  NO 1498A-2
   VILLAGE MAROL, ANDHERI EAST, MUMBAI, 400059, INDIA
SN 0301-4738
EI 1998-3689
J9 INDIAN J OPHTHALMOL
JI Indian J. Ophthalmol.
PD JAN
PY 2016
VL 64
IS 1
BP 55
EP 61
DI 10.4103/0301-4738.178153
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DH7ID
UT WOS:000372965700010
PM 26953025
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Reille-Seroussi, M
   Gaucher, JF
   Desole, C
   Gagey-Eilstein, N
   Brachet, F
   Broutin, I
   Vidal, M
   Broussy, S
AF Reille-Seroussi, Marie
   Gaucher, Jean-Francois
   Desole, Claudia
   Gagey-Eilstein, Nathalie
   Brachet, Franck
   Broutin, Isabelle
   Vidal, Michel
   Broussy, Sylvain
TI Vascular Endothelial Growth Factor Peptide Ligands Explored by
   Competition Assay and Isothermal Titration Calorimetry
SO BIOCHEMISTRY
LA English
DT Article
ID ORGANIC SULFUR CHEMISTRY; BINDING; EFFICIENT; DESULFURIZATION;
   COMPENSATION; LANTHIONINE; CONTRIBUTE; AFFINITY; COMPLEX; SEDPHAT
AB The v114* cyclic peptide has been identified as a tight vascular endothelial growth factor (VEGF) ligand. Here we report on the use of isothermal titration calorimetry (ITC), 96-well plate competition assay, and circular dichroism (CD) to explore the binding determinants of a new set of related peptides. Anti-VEGF antibodies are currently used in the clinic for regulating angiogenesis in cancer and age-related macular degeneration treatment. In this context, our aim is to develop smaller molecular entities with high affinity for the growth factor by a structure activity relationship approach. The cyclic disulfide peptide v114* was modified in several ways, including truncation, substitution, and variation of the size and nature of the cycle. The results indicated that truncation or substitution of the four N-terminal amino acids did not cause severe loss in affinity, allowing potential peptide labeling. Increase of the cycle size or substitution of the disulfide bridge with a thioether linkage drastically decreased the affinity, due to an enthalpy penalty. The leucine C-terminal residue positively contributed to affinity. Cysteine N-terminal acetylation induced favorable Delta Delta G degrees and Delta Delta H degrees of binding, which correlated with free peptide CD spectra changes. We also propose a biochemical model to extrapolate K-i from IC50 values measured in the displacement assay. These calculated K-i correlate well with the K-d values determined by extensive direct and reverse ITC measurements.
C1 [Reille-Seroussi, Marie; Desole, Claudia; Gagey-Eilstein, Nathalie; Vidal, Michel; Broussy, Sylvain] Univ Paris 05, CNRS, Fac Pharm, UMR 8638,Sorbonne Paris Cite, F-75006 Paris, France.
   [Gaucher, Jean-Francois; Brachet, Franck; Broutin, Isabelle] Univ Paris 05, CNRS, Fac Pharm, UMR 8015,Sorbonne Paris Cite, F-75006 Paris, France.
   [Vidal, Michel] Hop Cochin, APHP, UF Pharmacocinet & Pharmacochim, F-75014 Paris, France.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of
   Chemistry (INC); UDICE-French Research Universities; Universite Paris
   Cite; Universite de Franche-Comte; Centre National de la Recherche
   Scientifique (CNRS); CNRS - National Institute for Biology (INSB);
   UDICE-French Research Universities; Universite Paris Cite; Universite de
   Franche-Comte; Assistance Publique Hopitaux Paris (APHP); Hopital
   Universitaire Ambroise-Pare - APHP; Hopital Universitaire Cochin - APHP;
   UDICE-French Research Universities; Universite Paris Cite
RP Gaucher, JF (通讯作者)，Univ Paris 05, CNRS, Fac Pharm, UMR 8015,Sorbonne Paris Cite, 4 Ave Observ, F-75006 Paris, France.
EM jean-francois.gaucher@parisdescartes.fr;
   sylvain.broussy@parisdescartes.fr
RI Broutin, Isabelle/A-2003-2017; Vidal, Michel/ABA-3396-2020; Broussy,
   Sylvain/AAX-1833-2020
OI Broussy, Sylvain/0000-0003-3098-5317; Broutin,
   isabelle/0000-0001-9862-1232; Reille-Seroussi,
   Marie/0000-0002-4136-1297; Vidal, Michel/0000-0002-4858-1591
FU French National Research Agency [ANR-2010-BLAN-1533-03]; University
   Paris Descartes; CNRS ("Chaire de Partenariat CNRS"); ARC [DOC2013
   0606849]
FX Financial support from the French National Research Agency
   (ANR-2010-BLAN-1533-03), the University Paris Descartes, the CNRS
   ("Chaire de Partenariat CNRS" to S.B.), and the ARC (Grant DOC2013
   0606849 to M.R.-S.) is acknowledged.
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NR 39
TC 14
Z9 14
U1 0
U2 32
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 25
PY 2015
VL 54
IS 33
BP 5147
EP 5156
DI 10.1021/acs.biochem.5b00722
PG 10
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA CQ0YK
UT WOS:000360324300004
PM 26222917
DA 2022-11-30
ER

PT J
AU Guan, Y
   Cui, L
   Qu, Z
   Lu, L
   Wang, F
   Wu, Y
   Zhang, J
   Gao, F
   Tian, H
   Xu, L
   Xu, G
   Li, W
   Jin, Y
   Xu, GT
AF Guan, Y.
   Cui, L.
   Qu, Z.
   Lu, L.
   Wang, F.
   Wu, Y.
   Zhang, J.
   Gao, F.
   Tian, H.
   Xu, L.
   Xu, G.
   Li, W.
   Jin, Y.
   Xu, G-T
TI Subretinal Transplantation of Rat MSCs and Erythropoietin Gene Modified
   Rat MSCs for Protecting and Rescuing Degenerative Retina in Rats
SO CURRENT MOLECULAR MEDICINE
LA English
DT Article
DE Erythropoietin; gene therapy; rMSCs; retinal degeneration; RPE; Tet-on
ID MESENCHYMAL STEM-CELLS; MARROW STROMAL CELLS; PIGMENT EPITHELIAL-CELLS;
   BONE-MARROW; MACULAR DEGENERATION; RCS RATS; INTRAVITREAL
   ERYTHROPOIETIN; DIABETIC-RETINOPATHY; NEUROTROPHIC FACTORS;
   NERVOUS-SYSTEM
AB For degenerative retinal diseases, like the acquired form exemplified by age-related macular degeneration (AMD), there is currently no cure. This study was to explore a stem cell therapy and a stem cell-based gene therapy for sodium iodate (SI)-induced retinal degeneration in rats. Three cell types, i.e., rat mesenchymal stem cells (rMSCs) alone, erythropoietin (EPO) gene modified rMSCs (EPO-rMSCs) or doxycycline (DOX) inducible EPO expression rMSCs (Tet-on EPO-rMSCs), were transplanted into the subretinal spaces of SI-treated rats. The rMSCs were prepared for transplantation after 3 to 5 passages or modified with EPO gene. During the 8 weeks after the transplantation, the rats treated with rMSCs alone or with two types of EPO-rMSCs were all monitored with fundus examination, fundus fluorescein angiography (FFA) and electroretinogram. The transplantation efficiency of donor cells was examined for their survival, integration and differentiation. Following the transplantation, labeled donor cells were observed in subretinal space and adopted RPE morphology. EPO concentration in vitreous and retina of SI-treated rats which were transplanted with EPO-rMSCs or Tet-on EPO-rMSCs was markedly increased, in parallel with the improvement of retinal morphology and function. These findings suggest that rMSCs transplantation could be a new therapy for degenerative retinal diseases since it can protect and rescue RPE and retinal neurons, while EPO gene modification to rMSCs could be an even better option.
C1 [Guan, Y.; Lu, L.; Wang, F.; Zhang, J.; Gao, F.; Tian, H.; Xu, L.; Li, W.; Xu, G-T] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Ophthalmol, Shanghai 200092, Peoples R China.
   [Guan, Y.; Lu, L.; Wang, F.; Zhang, J.; Gao, F.; Tian, H.; Xu, L.; Li, W.; Xu, G-T] Tongji Univ, Sch Med, Tongji Eye Inst, Shanghai 200092, Peoples R China.
   [Guan, Y.; Lu, L.; Wang, F.; Zhang, J.; Gao, F.; Tian, H.; Xu, L.; Li, W.; Xu, G-T] Tongji Univ, Sch Med, Tongji Stem Cell Res Ctr, Shanghai 200092, Peoples R China.
   [Cui, L.; Qu, Z.; Wang, F.; Jin, Y.; Xu, G-T] Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Shanghai 200025, Peoples R China.
   [Cui, L.; Qu, Z.; Wu, Y.; Jin, Y.; Xu, G-T] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China.
   [Xu, G.] Suzhou Univ, Dept Ophthalmol, Affiliated Hosp 2, Suzhou 215006, Peoples R China.
   [Li, W.] Drexel Univ, Coll Med, Dept Ophthalmol, Philadelphia, PA 19107 USA.
   [Xu, G-T] Tongji Univ, Sch Med, Inst Nutr Sci, Shanghai 200092, Peoples R China.
C3 Tongji University; Tongji University; Tongji University; Shanghai Jiao
   Tong University; Chinese Academy of Sciences; Shanghai Institutes for
   Biological Sciences, CAS; Soochow University - China; Drexel University;
   Chinese Academy of Sciences; Tongji University
RP Li, W (通讯作者)，Drexel Univ, Coll Med, Dept Ophthalmol, 219 North Broad St 3FL, Philadelphia, PA 19107 USA.
EM weiye.li@drexelmed.edu; yjin@sibs.ac.cn; gtxu@tongji.edu.cn
RI Guan, Yuan/B-4986-2019
OI , jin ying/0000-0003-0070-2048
FU National Key Basic Research Program of China (973 Program) [2013
   CB967500, 2012CBA01308, 2010CB945201, 2011CB 965102, 2009CB941103,
   2011AA020106, 2011DFB 30010, 2012AA020906]; National Natural Science
   Foundation of China [31171419, 30700401, 91019929]; Science and
   Technology Commission of Shanghai [11DZ1920904]
FX This work was supported by the following grants: National Key Basic
   Research Program of China (973 Program) (2013 CB967500, 2012CBA01308,
   2010CB945201, 2011CB 965102, 2009CB941103, 2011AA020106, 2011DFB 30010,
   2012AA020906), National Natural Science Foundation of China (31171419,
   30700401, 91019929) and Science and Technology Commission of Shanghai
   (11DZ1920904).
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NR 52
TC 49
Z9 49
U1 1
U2 11
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1566-5240
EI 1875-5666
J9 CURR MOL MED
JI Curr. Mol. Med.
PD NOV
PY 2013
VL 13
IS 9
BP 1419
EP 1431
PG 13
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA 258GC
UT WOS:000327446300003
PM 23971737
DA 2022-11-30
ER

PT J
AU Almeida, A
   Kaliki, S
   Shields, CL
AF Almeida, Ana
   Kaliki, Swathi
   Shields, Carol L.
TI Autofluorescence of intraocular tumours
SO CURRENT OPINION IN OPHTHALMOLOGY
LA English
DT Review
DE autofluorescence; eye; fundus; intraocular; tumour
ID RETINAL-PIGMENT EPITHELIUM; CHOROIDAL MELANOCYTIC LESIONS; INDOCYANINE
   GREEN ANGIOGRAPHY; FUNDUS AUTOFLUORESCENCE; CONGENITAL HYPERTROPHY;
   CONSECUTIVE EYES; MELANOMA; OSTEOMA; RETINOBLASTOMA; FLUORESCEIN
AB Purpose of review
   Fundus autofluorescence is a noninvasive technique for evaluation of intrinsic autofluorescence of the tissues within the eye. In recent years, autofluorescence has become an important diagnostic tool for the assessment of various ocular diseases such as age-related macular degeneration and retinal dystrophies. In this report, we review the recent literature on autofluorescence of intraocular tumours.
   Recent findings
   The autofluorescence features of intraocular tumours range from bright hyperautofluorescence to dark hypoautofluorescence. The fundus autofluorescence generally represents the status of the overlying retinal pigment epithelium (RPE). Choroidal nevi typically have overlying hypoautofluorescence from chronic RPE atrophy as opposed to choroidal melanoma that exhibits hyperautofluorescence from overlying lipofuscin within RPE (orange pigment) and free fluorophores within fresh subretinal fluid. Choroidal metastases demonstrate overlying hyperautofluorescence that correlates to focal RPE accumulation of lipofuscin as well as subretinal fluid, particularly on the fresh advancing tumour margin. Choroidal haemangioma displays overlying hyperautofluorescence from lipofuscin within RPE and fresh subretinal fluid, but when choroidal haemangioma is chronic with resolved fluid, there is often overlying hypoautofluorescence from RPE atrophy. Congenital hypertrophy of the RPE is characterized by marked hypoautofluorescence of the RPE lesion and trace hyperautofluorescence within the lacunae.
   Summary
   Autofluorescence is a noninvasive, valuable diagnostic tool for assessment of intraocular tumours, based primarily on the effects on the overlying RPE. Some findings are strongly characteristic of certain tumours, particularly the bright hyperautofluorescence overlying small choroidal melanoma and the dark hypoautofluorescence of congenital hypertrophy of the RPE.
C1 [Almeida, Ana; Kaliki, Swathi; Shields, Carol L.] Thomas Jefferson Univ, Wills Eye Inst, Oncol Serv, Philadelphia, PA 19107 USA.
   [Almeida, Ana] Ctr Hosp Lisboa Ocidental, Hosp Egas Moniz, Ophthalmol Serv, Lisbon, Portugal.
   [Kaliki, Swathi] LV Prasad Eye Inst, Ocular Oncol Serv, Hyderabad, Andhra Pradesh, India.
C3 Jefferson University; Centro Hospitalar de Lisboa Ocidental, EPE; Egas
   Moniz Hospital; Universidade de Lisboa; L. V. Prasad Eye Institute
RP Shields, CL (通讯作者)，Wills Eye Inst, Ocular Oncol Serv, Suite 1440,840 Walnut St, Philadelphia, PA 19107 USA.
EM carol.shields@shieldsoncology.com
RI Kaliki, Swathi/C-2529-2018
FU Carlos G. Bianciotto Retinoblastoma Research Fund c/o the Eye Tumor
   Research Foundation, Philadelphia, Pennsylvania, USA; Lucille Wiedman
   Fund for Pediatric Eye Cancer, Philadelphia, Pennsylvania, USA; Lift for
   a Cure, Morrisdale, Pennsylvania, USA; Eye Tumor Research Foundation,
   Philadelphia, Pennsylvania, USA
FX Support provided by the Carlos G. Bianciotto Retinoblastoma Research
   Fund c/o the Eye Tumor Research Foundation, Philadelphia, Pennsylvania,
   USA (C.L.S.), The Lucille Wiedman Fund for Pediatric Eye Cancer,
   Philadelphia, Pennsylvania, USA (C.L.S.), Lift for a Cure, Morrisdale,
   Pennsylvania, USA (C.L.S.) and the Eye Tumor Research Foundation
   (C.L.S.), Philadelphia, Pennsylvania, USA.
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NR 41
TC 35
Z9 38
U1 0
U2 17
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8738
J9 CURR OPIN OPHTHALMOL
JI Curr. Opin. Ophthalmol.
PD MAY
PY 2013
VL 24
IS 3
BP 222
EP 232
DI 10.1097/ICU.0b013e32835f8ba1
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 123ML
UT WOS:000317394000007
PM 23429597
DA 2022-11-30
ER

PT J
AU Gan, W
   Wu, J
   Lu, L
   Xiao, X
   Huang, H
   Wang, FL
   Zhu, JW
   Sun, L
   Liu, G
   Pan, Y
   Li, HX
   Lin, X
   Chen, Y
AF Gan, Wei
   Wu, Johnna
   Lu, Ling
   Xiao, Xu
   Huang, Heng
   Wang, Fulong
   Zhu, Jingwen
   Sun, Liang
   Liu, Gang
   Pan, Yi
   Li, Huaixing
   Lin, Xu
   Chen, Yan
TI Associations of CFH Polymorphisms and CFHR1-CFHR3 Deletion with Blood
   Pressure and Hypertension in Chinese Population
SO PLOS ONE
LA English
DT Article
ID C-REACTIVE PROTEIN; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   COMPLEMENT C3; MYOCARDIAL-INFARCTION; SERUM C3; RISK; VARIANT;
   SUSCEPTIBILITY; INFLAMMATION
AB Dysregulation of the complement system has been linked to pathogenesis of hypertension. However, whether genetic changes of complement factor H (CFH) and its related genes are associated with hypertension is unknown. We genotyped three SNPs in the CFH gene cluster that are closely linked to age-related macular degeneration, namely rs1061170 (Y402H), rs2274700 (A473A) and rs7542235 (CFHR1-3 Delta), and tested for their associations with blood pressure and hypertension risk in a population-based cohort including 3,210 unrelated Chinese Hans (50-70 years of age) from Beijing and Shanghai. We found that rs2274700 (A473A) and rs7542235 (CFHR1-3 Delta) were both significantly associated with diastolic blood pressure (DBP) (beta = 0.632-1.431, P <= 0.038) and systolic blood pressure (SBP) (beta = 1.567-4.445, P <= 0.008), and rs2274700 (A473A) was associated with hypertension risk (OR [95%CI]: 1.175 [1.005-1.373], P = 0.048). Notably, the associations of rs2274700 (A473A) with DBP (P = 2.1x10(-3)), SBP (P = 8x10(-5)) and hypertension risk (P = 7.9x10(-3)) were significant only in the individuals with low CRP levels (<2.0 mg/l), but not in those with CRP levels >= 2.0 mg/l (P >= 0.0807) (P for interaction <= 0.0467). However, no significant association between rs1061170 (Y402H) and blood pressure or hypertension risk was observed (P >= 0.259). In conclusion, our results suggest that genetic variations in CFH and its related genes may contribute to hypertension risk in Chinese Hans.
C1 [Gan, Wei; Wu, Johnna; Lu, Ling; Huang, Heng; Wang, Fulong; Zhu, Jingwen; Sun, Liang; Liu, Gang; Pan, Yi; Li, Huaixing; Lin, Xu; Chen, Yan] Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China.
   [Xiao, Xu] Sichuan Prov Peoples Hosp, Dept Emergency Med, Chengdu, Peoples R China.
C3 Chinese Academy of Sciences; Shanghai Institutes for Biological
   Sciences, CAS; Sichuan Provincial People's Hospital
RP Gan, W (通讯作者)，Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China.
EM lihx@sibs.ac.cn; xlin@sibs.ac.cn; ychen3@sibs.ac.cn
RI Wang, Fulong/AAY-1178-2021; Liu, Gang/H-6420-2019
OI Liu, Gang/0000-0002-1430-3016; Wang, Fulong/0000-0002-7083-9675
FU Ministry of Science and Technology of China [2012CB524900,
   2010CB529506]; National Natural Science Foundation of China [30830037,
   81021002, 81130077]; Chinese Academy of Sciences [KSCX2-EW-R-08,
   KSCX2-EW-R-10]
FX This work was supported by research grants from Ministry of Science and
   Technology of China (2012CB524900 to Y.C. and 2010CB529506 to Y.P.),
   National Natural Science Foundation of China (30830037, 81021002 and
   81130077 to Y.C.), and Chinese Academy of Sciences (KSCX2-EW-R-08 to
   Y.C. and KSCX2-EW-R-10 to X. L.). 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 29
TC 10
Z9 10
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 JUL 25
PY 2012
VL 7
IS 7
AR e42010
DI 10.1371/journal.pone.0042010
PG 5
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 979GX
UT WOS:000306806600156
PM 22848687
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Hiraoka, M
   Inoue, K
   Kawano, H
   Takada, M
AF Hiraoka, Mari
   Inoue, Kenichi
   Kawano, Hitoshi
   Takada, Masahiko
TI Localization of Papillofoveal Bundles in Primates
SO ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY
   BIOLOGY
LA English
DT Article
DE papillofoveal bundle; carbocyanine dye; primate optic nerve; age-related
   macular degeneration; glaucoma
ID NERVE-FIBER LAYER; HUMAN OPTIC-NERVE; RETINA; HEAD; ORGANIZATION
AB Axons in the fovea are precisely organized to ensure accurate vision. We investigated the morphologic characteristics and localization of nerve bundles in the optic nerve in primates. Macaque eyes were studied for conventional and immunostaining, and also marmoset eyes for carbocyanine dye tracing. Locally confined lesions associated with similar findings to human age-related macular degeneration (ARMD) were also evaluated. Axons of retinal ganglion cells formed fasciculi near their origin, and these fasciculi formed bundles thereafter. In the retinal nerve fiber layer, ascending bundles assembled stratification adding proximal bundle underneath successively. Bundles in the arcuate zone displayed a characteristic fine, parallel arrangement, whereas those in the outside zone intermingled with undefined reticular bundles as they approached the optic nerve head. Macular bundles remained in groups and were distributed in the temporal wedge of the optic nerve head. Orthograde and retrograde tracing revealed that these bundles formed confined groups of various sizes and, ultimately, a specific group of small bundles located in the innermost row, near the central vessels. In addition, these bundles showed evidence of focal degenerative deterioration in eyes with ARMD. Papillomacular bundles have a characteristic alignment and configuration. Foveal bundles that compose the confined group closest to the optic trunk (which we term papillofoveal bundles) appear to have functional significance with respect to the isolated lesions that accompany central vision loss or preservation. Anat Rec, 2012. (C) 2011 Wiley Periodicals, Inc.
C1 [Hiraoka, Mari] Tokyo Metropolitan Inst Med Sci, Lab Brain Dev, Setagaya Ku, Tokyo 1568506, Japan.
   [Inoue, Kenichi; Takada, Masahiko] Kyoto Univ, Primate Res Inst, Syst Neurosci Sect, Inuyama, Aichi 4848506, Japan.
   [Kawano, Hitoshi] Tokyo Metropolitan Inst Med Sci, Lab Neuroregenerat, Setagaya Ku, Tokyo 1568506, Japan.
C3 Tokyo Metropolitan Institute of Medical Science; Kyoto University; Tokyo
   Metropolitan Institute of Medical Science
RP Hiraoka, M (通讯作者)，Cent Eye Infirm, 1-24-15 Nukui Kitamachi, Tokyo 1840015, Japan.
EM mari9190@true.ocn.ne.jp
RI Inoue, Ken-ichi/K-4103-2015
OI Inoue, Ken-ichi/0000-0002-5683-5280
FU Grants-in-Aid for Scientific Research [22650063, 23500422] Funding
   Source: KAKEN
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PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
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PY 2012
VL 295
IS 2
BP 347
EP 354
DI 10.1002/ar.21519
PG 8
WC Anatomy & Morphology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Anatomy & Morphology
GA 874UD
UT WOS:000298982700018
PM 22190466
DA 2022-11-30
ER

PT J
AU Ni, X
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AF Ni, X.
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TI Nucleic Acid Aptamers: Clinical Applications and Promising New Horizons
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Aptamers; clinical trial; imaging; nanoparticle; oligonucleotides;
   SELEX; siRNA; target therapy
ID HUMAN PROSTATE-CANCER; VON-WILLEBRAND-FACTOR; ENDOTHELIAL GROWTH-FACTOR;
   NF-KAPPA-B; IN-VIVO; SIRNA CHIMERAS; OCULAR NEOVASCULARIZATION;
   VASCULAR-PERMEABILITY; MEMBRANE ANTIGEN; RNA MOLECULES
AB Aptamers are a special class of nucleic acid molecules that are beginning to be investigated for clinical use. These small RNA/DNA molecules can form secondary and tertiary structures capable of specifically binding proteins or other cellular targets; they are essentially a chemical equivalent of antibodies. Aptamers have the advantage of being highly specific, relatively small in size, and non-immunogenic. Since the discovery of aptamers in the early 1990s, great efforts have been made to make them clinically relevant for diseases like cancer, HIV, and macular degeneration. In the last two decades, many aptamers have been clinically developed as inhibitors for targets such as vascular endothelial growth factor (VEGF) and thrombin. The first aptamer based therapeutic was FDA approved in 2004 for the treatment of age-related macular degeneration and several other aptamers are currently being evaluated in clinical trials. With advances in targeted-therapy, imaging, and nanotechnology, aptamers are readily considered as potential targeting ligands because of their chemical synthesis and ease of modification for conjugation. Preclinical studies using aptamer-siRNA chimeras and aptamer targeted nanoparticle therapeutics have been very successful in mouse models of cancer and HIV. In summary aptamers are in several stages of development, from pre-clinical studies to clinical trials and even as FDA approved therapeutics. In this review, we will discuss the current state of aptamers in clinical trials as well as some promising aptamers in pre-clinical development.
C1 [Lupold, S. E.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
   [Ni, X.; Castanares, M.; Mukherjee, A.; Lupold, S. E.] Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA.
   [Lupold, S. E.] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins
   University; Johns Hopkins University
RP Lupold, SE (通讯作者)，Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, 600 N Wolfe St,Pk 209, Baltimore, MD 21287 USA.
EM slupold@jhmi.edu
FU NIH/NCI [5P50CA058236]; NIGMS [F31GM79838, 5R01CA143299-02]; Patrick C
   Walsh Prostate Cancer Research Fund; Prostate Cancer Foundation;
   Safeway; NATIONAL CANCER INSTITUTE [R01CA143299, P50CA058236,
   P30CA006973] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL
   MEDICAL SCIENCES [F31GM079838] Funding Source: NIH RePORTER
FX We would like to thank the following funding sources: NIH/NCI
   5P50CA058236 (XN, SEL), NIGMS F31GM79838 MC); 5R01CA143299- 02 (SEL),
   the Patrick C Walsh Prostate Cancer Research Fund, the Prostate Cancer
   Foundation, and Safeway (AM, SEL).
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NR 85
TC 196
Z9 225
U1 4
U2 127
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 0929-8673
EI 1875-533X
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD SEP
PY 2011
VL 18
IS 27
BP 4206
EP 4214
DI 10.2174/092986711797189600
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
   Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 827SE
UT WOS:000295447500012
PM 21838685
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Li, SK
   Liddell, MR
   Wen, H
AF Li, S. Kevin
   Liddell, Mark R.
   Wen, He
TI Effective electrophoretic mobilities and charges of anti-VEGF proteins
   determined by capillary zone electrophoresis
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Electrophoresis; Electrophoretic mobility; Effective charge; Capillary
   zone electrophoresis; Anti-VEGF protein
ID HUMAN EPIDERMAL MEMBRANE; IONTOPHORETIC TRANSPORT; MONOCLONAL-ANTIBODY;
   DRUG-DELIVERY; SYNTHETIC MEMBRANE; HUMAN SCLERA; PHARMACEUTICALS;
   BEVACIZUMAB; PERMEATION; BINDING
AB Macromolecules such as therapeutic proteins currently serve an important role in the treatment of eye diseases such as wet age-related macular degeneration and diabetic retinopathy. Particularly, bevacizumab and ranibizumab have been shown to be effective in the treatment of these diseases. Iontophoresis can be employed to enhance ocular delivery of these macromolecules, but the lack of information on the properties of these macromolecules has hindered its development. The objectives of the present study were to determine the effective electrophoretic mobilities and charges of bevacizumab, ranibizumab, and model compound polystyrene sulfonate (PSS) using capillary zone electrophoresis. Salicylate, lidocaine, and bovine serum albumin (BSA), which have known electrophoretic mobilities in the literature, were also studied to validate the present technique. The hydrodynamic radii and diffusion coefficients of BSA, bevacizumab, ranibizumab, and PSS were measured by dynamic light scattering. The effective charges were calculated using the Einstein relation between diffusion coefficient and electrophoretic mobility and the Henry equation. The results show that bevacizumab and ranibizumab have low electrophoretic mobilities and are net negatively charged in phosphate buffered saline (PBS) of pH 7.4 and 0.16 M ionic strength. PSS has high negative charge but the electrophoretic mobility in PBS is lower than that expected from the polymer structure. The present study demonstrated that capillary electrophoresis could be used to characterize the mobility and charge properties of drug candidates in the development of iontophoretic drug delivery. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Li, S. Kevin; Liddell, Mark R.; Wen, He] Univ Cincinnati, Coll Pharm, Div Pharmaceut Sci, Cincinnati, OH 45267 USA.
C3 University System of Ohio; University of Cincinnati
RP Li, SK (通讯作者)，Univ Cincinnati, Coll Pharm, Div Pharmaceut Sci, 3225 Eden Ave,136 HPB, Cincinnati, OH 45267 USA.
EM kevin.li@uc.edu
RI Li, S. Kevin/AAF-4877-2019; Wen, He/GZL-8825-2022
OI Li, S. Kevin/0000-0001-8626-9630; 
FU NIH Roadmap for Medical Research [EY 015181, PN2 EY 018230]; NIH [R01 GM
   059944]; NATIONAL EYE INSTITUTE [R01EY015181, PN2EY018230] Funding
   Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
   [R01GM059944] Funding Source: NIH RePORTER
FX This research was supported in part by NIH Grant EY 015181. The authors
   thank Poonam Chopra for performing the preliminary experiments, Dr.
   Apryll Stalcup and Floyd Stanley for their help in the preliminary
   capillary electrophoresis study and helpful discussion, Dr. Peixuan Guo
   for providing the facility to conduct the experiments. The facility was
   supported by NIH Roadmap for Medical Research PN2 EY 018230 (to PG) and
   NIH R01 GM 059944 (to PG). The authors also thank Dr. Peng Jing and Dr.
   Anne Vonderheide for their help, Dr. Robert Hutchins and Dr. Stewart
   Krug for the Lucentis used in this study, and Dr. Tom Patapoff for the
   information on Lucentis and Avastin and helpful discussion.
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NR 40
TC 47
Z9 47
U1 1
U2 45
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD JUN 1
PY 2011
VL 55
IS 3
BP 603
EP 607
DI 10.1016/j.jpba.2010.12.027
PG 5
WC Chemistry, Analytical; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Pharmacology & Pharmacy
GA 751AM
UT WOS:000289589700032
PM 21269789
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Glenn, JV
   Stitt, AW
AF Glenn, Josephine V.
   Stitt, Alan W.
TI The role of advanced glycation end products in retinal ageing and
   disease
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Review
DE Ageing; Advanced glycation end product; RPE; AMD
ID PIGMENT EPITHELIAL-CELLS; MITOCHONDRIAL-DNA DAMAGE; AGE-RELATED
   MACULOPATHY; OPEN-ANGLE GLAUCOMA; OPTIC-NERVE HEAD; MACULAR
   DEGENERATION; EXTRACELLULAR-MATRIX; OXIDATIVE STRESS; MAILLARD REACTION;
   DIABETIC-RATS
AB The retina is exposed to a lifetime of potentially damaging environmental and physiological factors that make the component cells exquisitely sensitive to age-related processes. Retinal ageing is complex and a raft of abnormalities can accumulate in all layers of the retina. Some of this pathology serves as a sinister preamble to serious conditions such as age-related macular degeneration (AMD) which remains the leading cause of irreversible blindness in the Western world.
   The formation of advanced glycation end products (AGEs) is a natural function of ageing but accumulation of these adducts also represents a key pathophysiological event in a range of important human diseases. AGEs act as mediators of neurodegeneration, induce irreversible changes in the extracellular matrix, vascular dysfunction and pro-inflammatory signalling. Since many cells and tissues of the eye are profoundly influenced by such processes, it is fitting that advanced glycation is now receiving considerable attention as a possible pathogenic factor in visual disorders.
   This review presents the current evidence for a pathogenic role for AGEs and activation of the receptor for AGEs (RAGE) in initiation and progression of retinal disease. It draws upon the clinical and experimental literature and highlights the opportunities for further research that would definitively establish these adducts as important instigators of retinal disease. The therapeutic potential for novel agents that can ameliorate AGE formation of attenuate RAGE signalling in the retina is also discussed. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Glenn, Josephine V.; Stitt, Alan W.] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Vis & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland.
C3 Queens University Belfast
RP Stitt, AW (通讯作者)，Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Vis & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland.
EM a.stitt@qub.ac.uk
RI Stitt, Alan/A-9842-2009
OI Stitt, Alan/0000-0002-8647-9918
FU Action Medical Research; Medical Research Council (MRC) [G0600053];
   Medical Research Council [G0600053] Funding Source: researchfish; MRC
   [G0600053] Funding Source: UKRI
FX We also acknowledge Action Medical Research and the Medical Research
   Council (MRC) (grant no.G0600053) who support our research in retinal
   ageing.
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NR 131
TC 81
Z9 90
U1 0
U2 26
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4165
EI 1872-8006
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD OCT
PY 2009
VL 1790
IS 10
BP 1109
EP 1116
DI 10.1016/j.bbagen.2009.04.016
PG 8
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 503EO
UT WOS:000270516100018
PM 19409449
DA 2022-11-30
ER

PT J
AU Bretillon, L
   Acar, N
   Seeliger, MW
   Santos, M
   Maire, MA
   Juaneda, P
   Martine, L
   Gregoire, S
   Joffre, C
   Bron, AM
   Creuzot-Garcher, C
AF Bretillon, Lionel
   Acar, Niyazi
   Seeliger, Mathias W.
   Santos, Mylene
   Maire, Marie Annick
   Juaneda, Pierre
   Martine, Lucy
   Gregoire, Stephane
   Joffre, Corinne
   Bron, Alain M.
   Creuzot-Garcher, Catherine
TI ApoB100,LDLR-/- mice exhibit reduced electroretinographic response and
   cholesteryl esters deposits in the retina
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; HIGH-FAT DIET; HUMAN ATHEROSCLEROTIC LESIONS;
   RECEPTOR-NEGATIVE MICE; HUMAN APOLIPOPROTEIN-B; HUMAN BRUCHS MEMBRANE;
   ROD OUTER SEGMENTS; MACULAR DEGENERATION; TRANSGENIC MICE; BASAL
   DEPOSITS
AB PURPOSE. To evaluate the retinal phenotype of 7- and 14-month-old apoB100,LDLR-/- mice, a relevant animal model of lipid metabolism dysfunction.
   METHODS. Single-flash electroretinograms were obtained from 7- and 14-month-old apoB100,LDLR-/- and control mice fed a standard diet under both scotopic and photopic conditions. Visual cycle retinoids were analyzed in eyes from dark-adapted mice. Retinal and choroidal vascularization was evaluated with scanning laser ophthalmoscopy. Fatty acids were analyzed in the retina. Esterified and free cholesterol was detected in eye cryosections.
   RESULTS. Scotopic and photopic b-wave amplitudes were significantly reduced in apoB100,LDLR-/- mice compared with control mice at 7 and 14 months of age ( between -25% and -35% in 7-month-old animals and between -50% and -60% in 14-month-old animals at 25 cds/m(2)). Esterified cholesterol was found to accumulate at the basement of the retinal pigment epithelium in apoB100,LDLR-/- mouse eyes. On the contrary, no significant changes in the retinal profile of fatty acids and visual retinoids were observed in apoB100,LDLR-/- mice compared with control animals.
   CONCLUSIONS. The exclusive expression of apoB100 in LDL receptor-null mouse altered the ERG profile, without modifying the visual cycle of retinoids and led to cholesterol deposition in the retina. These findings clearly suggest the role of cholesterol metabolism in the functioning of the retina and possibly in the etiology of ocular diseases, including age-related macular degeneration.
C1 [Bron, Alain M.; Creuzot-Garcher, Catherine] Univ Bourgogne, UMR FLAVIC 1129, Eye & Nutr Res Grp, INRA, F-21000 Dijon, France.
   [Seeliger, Mathias W.] Univ Tubingen, Inst Opthalm Res, Ctr Ophthalmol, Ocular Neurodegenerat Res Grp, Tubingen, Germany.
   [Bron, Alain M.; Creuzot-Garcher, Catherine] Univ Hosp, Dept Ophthalmol, F-21000 Dijon, France.
C3 INRAE; Institut Agro; AgroSup Dijon; Universite de Bourgogne; Eberhard
   Karls University of Tubingen; Eberhard Karls University Hospital; CHU
   Dijon Bourgogne
RP Bretillon, L (通讯作者)，INRA, Unite FLAVIC, Equipe CEil & Nutr, 17 Rue Sully,BP 86510, F-21065 Dijion, France.
EM lionel.bretillon@dijon.inra.fr
RI Bron, Alain/AAP-8010-2020
OI Bron, Alain/0000-0002-7265-931X; Bretillon, Lionel/0000-0002-6957-100X;
   JOFFRE, Corinne/0000-0001-8327-3554
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NR 50
TC 40
Z9 40
U1 0
U2 4
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 2008
VL 49
IS 4
BP 1307
EP 1314
DI 10.1167/iovs.07-0808
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 282ON
UT WOS:000254577200004
PM 18385042
DA 2022-11-30
ER

PT J
AU Suuronen, T
   Nuutinen, T
   Ryhanen, T
   Kaarniranta, K
   Salminen, A
AF Suuronen, Tiina
   Nuutinen, Tapio
   Ryhanen, Tuomas
   Kaarniranta, Kai
   Salminen, Antero
TI Epigenetic regulation of clusterin/apolipoprotein J expression in
   retinal pigment epithelial cells
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE 5-aza-2 '-deoxycytidine; HDAC; histone deacetylase inhibitor; macular
   degeneration; trichostatin A; valproate
ID DNA METHYLATION; IN-VITRO; CLUSTERIN; INHIBITORS; INFLAMMATION; THERAPY;
   STRESS; DRUSEN; GENE
AB Age-related macular degeneration (AMD) is the leading cause of blindness worldwide. AMD is characterized by the deposition of drusen aggregates under the retinal pigment epithelium (RPE). Clusterin/apo J, a multifunctional secreted chaperone, is one of the major proteins accumulating in drusen deposits. The regulation of clusterin expression is not well characterized but the promoter of clusterin contains a CpG-rich methylation domain. Since aging affects both DNA methylation and historic acetylation status, the epigenetic regulation might have an important role in clusterin/apo J expression.
   Our purpose was to elucidate whether the induction of DNA hypomethylation with 5-aza-2'-deoxycytidine (AZA) and histone hyperacetylation with trichostatin A (TSA) could affect the clusterin transcription, protein levels, and secretion in retinal pigment epithelial cells. We observed that both TSA and AZA treatments induced a prominent increase in the expression levels of clusterin mRNA and protein in ARPE-19 cells, as well as in the secretion of clusterin protein. Furthermore, valproic acid, an antiepileptic drug and a recently identified inhibitor of histone deacetylases (HDAC), induced a significant increase in clusterin protein expression and secretion in retinal pigment epithelial cells. HDAC inhibitors are characterized as inhibitors of angiogenesis, and clusterin as a complement inhibitor. Our results indicate that epigenetic factors regulate the clusterin expression of RPE cells and thus might affect the pathogenesis of AMD via the inhibition of angiogenesis and inflammation. (c) 2007 Elsevier Inc. All rights reserved.
C1 Univ Kuopio, Dept Neurosci & Neurol, FIN-70211 Kuopio, Finland.
   Univ Kuopio, Dept Ophthalmol, FIN-70211 Kuopio, Finland.
   Univ Hosp Kuopio, Dept Neurol, FIN-70211 Kuopio, Finland.
C3 University of Eastern Finland; University of Eastern Finland; Kuopio
   University Hospital
RP Salminen, A (通讯作者)，Univ Kuopio, Dept Neurosci & Neurol, POB 1627, FIN-70211 Kuopio, Finland.
EM antero.salminen@uku.fi
OI Kaarniranta, Kai/0000-0003-2600-8679
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NR 31
TC 61
Z9 65
U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUN 1
PY 2007
VL 357
IS 2
BP 397
EP 401
DI 10.1016/j.bbrc.2007.03.135
PG 5
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 164SE
UT WOS:000246253700012
PM 17420006
DA 2022-11-30
ER

PT J
AU Qin, SF
   McLaughlin, AP
   De Vries, GW
AF Qin, Suofu
   McLaughlin, Anne P.
   De Vries, Gerald W.
TI Protection of RPE cells from oxidative injury by
   15-deoxy-Delta(12,14)-prostaglandin J(2) by augmenting GSH and
   activating MAPK
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; AMINO-ACID-SEQUENCE; GENE-EXPRESSION;
   RECEPTOR-GAMMA; PROSTAGLANDIN J(2); SUBUNIT GENE; INDUCTION;
   TRANSCRIPTION; APOPTOSIS; PROTEIN
AB PURPOSE. The goal of this study was to identify the mechanisms by which 15-deoxy-Delta(12,14)-prostaglandin J(2) (dPGJ(2)) protects RPE cells from oxidative injury.
   METHODS. Cell viability was determined by MTT assay. Protein expression and activation of signaling molecules were detected by Western blot. Reduced glutathione (GSH) was determined by a colorimetric assay kit. PPAR gamma expression was knockdown by small interfering (si) RNA technique.
   RESULTS. dPGJ(2) protected ARPE19 cells from oxidative injury, whereas the synthetic PPAR gamma agonists AGN195037 and rosiglitazone had no effect. PPAR gamma knockdown also did not affect dPGJ(2)'s protective activity. dPGJ(2) upregulated GSH synthesis via induction of glutamylcysteine ligase. GSH depletion sensitized cells to oxidative stress and completely reversed the protective effect of dPGJ(2). dPGJ(2) activated ERK, JNK, and p38; GSH induction by dPGJ(2) depended partially on JNK and p38. In addition, dPGJ(2) significantly extended hydrogen peroxide-induced activation of JNK and p38, but not of Akt. Inhibition of MEK, JNK, and p38 abolished dPGJ2's protection of ARPE19 cells from oxidative injury, whereas inhibiting PI3K/Akt pathway failed to affect dPGJ(2)'s protective effect. Heme oxygenase-1 was strongly induced by dPGJ(2) but was not associated with protection.
   CONCLUSIONS. Independent of its PPAR gamma activity, dPGJ(2) protected cells from oxidative stress by elevating GSH and enhancing MAPK activation. Thus, dPGJ(2) may delay the development of dry-type age-related macular degeneration.
C1 Allergan Pharmaceut Inc, Dept Sci Biol, Irvine, CA 92612 USA.
C3 AbbVie; Allergan
RP Qin, SF (通讯作者)，Allergan Pharmaceut Inc, Dept Sci Biol, 2525 Dupont Dr, Irvine, CA 92612 USA.
EM qin_suofu@allergan.com
OI Qin, Suofu/0000-0002-3323-8846
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NR 46
TC 48
Z9 52
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 NOV
PY 2006
VL 47
IS 11
BP 5098
EP 5105
DI 10.1167/iovs.06-0318
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 098XS
UT WOS:000241557500063
PM 17065531
DA 2022-11-30
ER

PT J
AU de Winter, LJM
   Hoyng, CB
   Froeling, PGAM
   Meulendijks, CFM
   van der Wilt, GJ
AF de Winter, LJM
   Hoyng, CB
   Froeling, PGAM
   Meulendijks, CFM
   van der Wilt, GJ
TI Prevalence of remediable disability due to low vision among
   institutionalised elderly people
SO GERONTOLOGY
LA English
DT Article
DE institutionalised elderly people; visual disability; low-vision aids;
   quality of care
ID NURSING-HOME RESIDENTS; QUALITY-OF-LIFE; VISUAL IMPAIRMENT; FUNCTIONAL
   IMPAIRMENT; CATARACT-SURGERY; INDEX; VF-14; EUROQOL; DISEASE; SYSTEM
AB Background: Prevalence of remediable visual disability among institutionalised elderly people, resulting from inappropriate use or non-use of low-vision aids, is reported to be high, but largely rests on anecdotal evidence. Objective: To estimate the prevalence of binocular low vision and underlying eye diseases among institutionalised elderly people in a Dutch urban population and the size of remediable visual disability as the result of inappropriately corrected low vision. Methods: The design was a cross-sectional survey of 284 subjects with low vision (corrected binocular vision <0.4) in nursing homes and homes for the elderly in the Netherlands. Results: 284 of 610 eligible residents were examined. The prevalence of binocular low vision was 31.3%. Among elderly residents with low vision, prevalence of cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy was 77.9, 37.7, 5.2 and 5.2%, respectively. In 32 residents (41.6%), (non)-use of low-vision aids was considered inappropriate. In 50 residents (64.9%), visual disability was considered at least partially remediable, either through better use of low-vision aids, or through cataract extraction. Residents who were not optimally corrected for low vision were significantly more functionally impaired compared with their peers who were optimally corrected. Conclusion: Low vision is likely to be highly prevalent among institutionalised elderly. A significant amount of the associated visual disability may be remediable. Copyright (C) 2004 S. Karger AG, Basel.
C1 Univ Med Ctr, Dept Med Technol Assessment 253 MTA, NL-6500 HB Nijmegen, Netherlands.
   Univ Med Ctr, Dept Technol Assessment, NL-6500 HB Nijmegen, Netherlands.
   Univ Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands.
   Univ Med Ctr, Dept Nursing Home Med, NL-6500 HB Nijmegen, Netherlands.
C3 Radboud University Nijmegen; Radboud University Nijmegen; Radboud
   University Nijmegen; Radboud University Nijmegen
RP van der Wilt, GJ (通讯作者)，Univ Med Ctr, Dept Med Technol Assessment 253 MTA, POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM G.vanderWilt@mta.umcn.nl
RI van der Wilt, G.J./H-8120-2014; Hoyng, C.B./H-8050-2014
OI van der Wilt, G.J./0000-0002-5856-762X; 
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NR 17
TC 20
Z9 20
U1 3
U2 5
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0304-324X
EI 1423-0003
J9 GERONTOLOGY
JI Gerontology
PY 2004
VL 50
IS 2
BP 96
EP 101
DI 10.1159/000075560
PG 6
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA 773NQ
UT WOS:000188930200007
PM 14963376
DA 2022-11-30
ER

PT J
AU Ida, H
   Boylan, SA
   Weigel, AL
   Hjelmeland, LM
AF Ida, H
   Boylan, SA
   Weigel, AL
   Hjelmeland, LM
TI Age-related changes in the transcriptional profile of mouse RPE/choroid
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE retinal pigmented epithelium; aging; cDNA microarray; choroid
ID RETINAL-PIGMENT EPITHELIUM; GENE-EXPRESSION PROFILE; MACULAR
   DEGENERATION; ANTIOXIDANT ENZYMES; BRUCHS MEMBRANE; SUSCEPTIBILITY;
   PHAGOCYTOSIS; MICROARRAYS; MODEL
AB To evaluate the age-related changes in gene expression occurring in the complex of retinal pigmented epithelium, Bruch's membrane, and choroid (RPE/choroid), we examined the gene expression profiles of young adult (2 mo) and old (24 mo) male C57BL/6 mice. cDNA probe sets from individual animals were synthesized using total RNA isolated from the RPE/choroid of each animal. Probes were amplified using the Clontech SMART system, radioactively labeled, and hybridized to two different Clontech Atlas mouse cDNA arrays. From each age group, three independent triplicates were hybridized to the arrays. Statistical analyses were performed using the Significance Analysis of Microarrays program (SAM version 1.13; Stanford University). Selected array results were confirmed by semi-quantitative RT-PCR analysis. Of 2,340 genes represented on the arrays, similar to60% were expressed in young and/or old mouse RPE/choroid. A moderate fraction (12%) of all expressed genes exhibited a statistically significant change in expression with age. Of these 150 genes, all but two, HMG14 and carboxypeptidase E, were upregulated with age. Many of these upregulated genes can be grouped into several broad functional categories: immune response, proteases and protease inhibitors, stress response, and neovascularization. RT-PCR results from six of six genes examined confirmed the differential change in expression with age of these genes. Our study provides likely candidate genes to further study their role in the development of age-related macular degeneration and other aging diseases affecting the RPE/choroid.
C1 Univ Calif Davis, Sch Med, Vitreoretinal Res Lab, Dept Biol Chem, Davis, CA 95616 USA.
   Univ Calif Davis, Dept Ophthalmol, Davis, CA 95616 USA.
C3 University of California System; University of California Davis;
   University of California System; University of California Davis
RP Hjelmeland, LM (通讯作者)，Univ Calif Davis, Sch Med, Vitreoretinal Res Lab, Dept Biol Chem, 1 Shields Ave, Davis, CA 95616 USA.
EM lmhjelmeland@ucdavis.edu
FU NATIONAL EYE INSTITUTE [P30EY012576] Funding Source: NIH RePORTER; NEI
   NIH HHS [P30-EY-12576, EY-06473] Funding Source: Medline
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NR 39
TC 32
Z9 33
U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
EI 1531-2267
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD NOV 11
PY 2003
VL 15
IS 3
BP 258
EP 262
DI 10.1152/physiolgenomics.00126.2003
PG 5
WC Cell Biology; Genetics & Heredity; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Genetics & Heredity; Physiology
GA 742BJ
UT WOS:000186495100010
PM 14519767
DA 2022-11-30
ER

PT J
AU Friedman, JS
   Faucher, M
   Hiscott, P
   Biron, VL
   Malenfant, M
   Turcotte, P
   Raymond, V
   Walter, MA
AF Friedman, JS
   Faucher, M
   Hiscott, P
   Biron, VL
   Malenfant, M
   Turcotte, P
   Raymond, V
   Walter, MA
TI Protein localization in the human eye and genetic screen of opticin
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID STATIONARY NIGHT BLINDNESS; RICH REPEAT PROTEIN; EXTRACELLULAR-MATRIX;
   CORNEA PLANA; MUTATIONS; KERATOCAN; CLONING; PEOPLE; FAMILY; MEMBER
AB The opticin (OPTC) gene encodes a protein that is a member of the small leucine-rich repeat protein (SLRP) family. OPTC is located on chromosome 1q31-q32 within an age-related macular degeneration (AMD) susceptibility locus. We have developed an affinity-purified N-terminal anti-opticin antibody and used it to examine opticin expression in human eye tissues. The antibody was also used for opticin protein localization in human eye sections. Immunoblots of human eye tissues detected a predominant band of approximately 62kDa in size in iris, trabecular meshwork/ciliary body, retina, vitreous, and optic nerve. Immunohistochemical experiments revealed that opticin is specifically localized in human cornea, iris, ciliary body, vitreous, choroid and retina. Due to opticin's protein profile in the eye, we have also screened OPTC for mutations in individuals with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG) or AMD. We identified four sequence variations, all of which were observed in normal controls except for the Arg229Cys change. Three amino acid substitutions (IIe182Thr, Arg229Cys and Arg325Trp) were in residues conserved in dog, mouse, pig and human. The Arg229Cys alteration was present in a homozygous state in one individual with neovascular AMD. Examination of the other AMD afflicted family members showed that the OPTC Arg229Cys variant did not segregate with the disorder within the family. The protein localization pattern of opticin and our preliminary screen of AMD patients suggest that a larger AMD patient screen may be warranted.
C1 Univ Alberta, Ocular Genet Lab, Dept Ophthalmol, Edmonton, AB T6G 2H7, Canada.
   Univ Alberta, Dept Med Genet, Edmonton, AB T6G 2H7, Canada.
   Laval Univ Hosp, CHUL, Res Ctr, Quebec City, PQ G1V 4G2, Canada.
   Univ Clin Dept, Unit Ophthalmol, Liverpool L69 3GA, Merseyside, England.
   CHU Laval, Dept Ophthalmol, Quebec City, PQ G1V 4G2, Canada.
   Univ Laval, Quebec City, PQ G1V 4G2, Canada.
C3 University of Alberta; University of Alberta; Laval University;
   University of Liverpool; Laval University; Laval University
RP Walter, MA (通讯作者)，Univ Alberta, Ocular Genet Lab, Dept Ophthalmol, Room 8-32,Med Sci Bldg, Edmonton, AB T6G 2H7, Canada.
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NR 20
TC 32
Z9 41
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAY 15
PY 2002
VL 11
IS 11
BP 1333
EP 1342
DI 10.1093/hmg/11.11.1333
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 556NQ
UT WOS:000175856200010
PM 12019215
OA Bronze
DA 2022-11-30
ER

PT J
AU DelGuidice, CE
   Ismaiel, OA
   Mylott, WR
   Yuan, MC
   Halquist, MS
AF DelGuidice, Catherine E.
   Ismaiel, Omnia A.
   Mylott, William R., Jr.
   Yuan, Moucun
   Halquist, Matthew S.
TI Intact quantitative bioanalytical method development and fit-for-purpose
   validation of a monoclonal antibody and its related fab fragment in
   human vitreous and aqueous humor using LC-HRMS
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Bevacizumab; Ranibizumab; VEGF; LC-HRMS; Bioanalytical method
   development; Monoclonal antibody; Intact protein quantitation; Orbitrap;
   Deconvolution; Top-down
ID ENDOTHELIAL GROWTH-FACTOR; SINGLE INTRAVITREAL INJECTION;
   MASS-SPECTROMETRY; INTRAOCULAR PHARMACOKINETICS; HUMAN PLASMA; PROTEIN;
   RANIBIZUMAB; BEVACIZUMAB; LEVEL; MS
AB Ranibizumab is an FDA-approved drug used to treat wet age-related macular degeneration (AMD), diabetic retinopathy, macular edema, and myopic choroidal neovascularization. Bevacizumab is another drug often used off-label to treat wet AMD. In order to reduce unwanted angiogenesis, ranibizumab and bevacizumab target circulating VEGF-A in the eye. Concentration levels in human vitreous and aqueous humor can be used to provide valuable efficacy information. However, vitreous and aqueous humor's aqueous environment, and vitreous humor's viscosity, as well as the stickiness of the analytes can provide bioanalytical challenges. In this manuscript, we describe the development, optimization, and fit-for-purpose validation of an LC-HRMS method designed for intact quantitative bioanalysis of ranibizumab and bevacizumab in human vitreous and aqueous humor following intravitreal administration. In order to fully develop this method, evaluations were conducted to optimize the conditions, including the data processing model (extracted ion chromatograms (XICs) vs deconvolution), carryover mitigation, sample preparation scheme optimization for surrogate and primary matrices, use of internal standard/immunocapture/deglycosylation, and optimization of the extraction and dilution procedure, as well as optimization of the liquid chromatography and mass spectrometry conditions. Once the method was fully optimized, a fit-for-purpose validation was conducted, including matrix parallelism, with a linear calibration range of 10 to 200 mu g/mL. The development of this intact quantitative method using LC-HRMS provides a proof-of-concept template for challenging, but valuable new and exciting bioanalytical techniques.
C1 [DelGuidice, Catherine E.; Halquist, Matthew S.] Virginia Commonwealth Univ, Sch Pharm, Dept Pharmaceut, Richmond, VA 23284 USA.
   [DelGuidice, Catherine E.; Mylott, William R., Jr.; Yuan, Moucun] PPD Labs, Richmond, VA 23230 USA.
   [Ismaiel, Omnia A.] Zagazig Univ, Fac Pharm, Dept Analyt Chem, Zagazig, Egypt.
C3 Virginia Commonwealth University; Egyptian Knowledge Bank (EKB); Zagazig
   University
RP DelGuidice, CE (通讯作者)，Virginia Commonwealth Univ, Sch Pharm, Dept Pharmaceut, Richmond, VA 23284 USA.; DelGuidice, CE (通讯作者)，PPD Labs, Richmond, VA 23230 USA.
EM delguidicece@vcu.edu
OI Ismaiel, Omnia/0000-0003-3680-621X
FU Virginia Commonwealth University School of Pharmacy and Pharmaceutical
   Product Development's Bioanalytical Laboratories in Richmond, VA
FX This study was supported by Virginia Commonwealth University School of
   Pharmacy and Pharmaceutical Product Development's Bioanalytical
   Laboratories in Richmond, VA.
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NR 50
TC 0
Z9 0
U1 1
U2 2
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
EI 1618-2650
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JUN
PY 2022
VL 414
IS 14
SI SI
BP 4189
EP 4202
DI 10.1007/s00216-022-04071-x
EA APR 2022
PG 14
WC Biochemical Research Methods; Chemistry, Analytical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 1Q8EW
UT WOS:000786084900002
PM 35451621
DA 2022-11-30
ER

PT J
AU Harsing, LG
   Szenasi, G
   Zelles, T
   Koles, L
AF Harsing, Laszlo G., Jr.
   Szenasi, Gabor
   Zelles, Tibor
   Koles, Laszlo
TI Purinergic-Glycinergic Interaction in Neurodegenerative and
   Neuroinflammatory Disorders of the Retina
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Review
DE retina; purinergic modulation; glycinergic neurotransmission; microglia;
   neuroinflammation; neurodegeneration; glycine transporters
ID TRANSPORTER TYPE-1 GLYT-1; CENTRAL-NERVOUS-SYSTEM; GANGLION-CELL DEATH;
   ADENOSINE RECEPTOR; MULLER CELLS; GLUTAMATE RELEASE; NMDA RECEPTORS;
   AMACRINE CELLS; POTENTIAL ROLE; M2 MICROGLIA
AB Neurodegenerative-neuroinflammatory disorders of the retina seriously hamper human vision. In searching for key factors that contribute to the development of these pathologies, we considered potential interactions among purinergic neuromodulation, glycinergic neurotransmission, and microglia activity in the retina. Energy deprivation at cellular levels is mainly due to impaired blood circulation leading to increased release of ATP and adenosine as well as glutamate and glycine. Interactions between these modulators and neurotransmitters are manifold. First, P2Y purinoceptor agonists facilitate reuptake of glycine by glycine transporter 1, while its inhibitors reduce reverse-mode operation; these events may lower extracellular glycine levels. The consequential changes in extracellular glycine concentration can lead to parallel changes in the activity of NR1/NR2B type NMDA receptors of which glycine is a mandatory agonist, and thereby may reduce neurodegenerative events in the retina. Second, P2Y purinoceptor agonists and glycine transporter 1 inhibitors may indirectly inhibit microglia activity by decreasing neuronal or glial glycine release in energy-compromised retina. These inhibitions may have a role in microglia activation, which is present during development and progression of neurodegenerative disorders such as glaucomatous and diabetic retinopathies and age-related macular degeneration or loss of retinal neurons caused by thromboembolic events. We have hypothesized that glycine transporter 1 inhibitors and P2Y purinoceptor agonists may have therapeutic importance in neurodegenerative-neuroinflammatory disorders of the retina by decreasing NR1/NR2B NMDA receptor activity and production and release of a series of proinflammatory cytokines from microglial cells.
C1 [Harsing, Laszlo G., Jr.; Zelles, Tibor; Koles, Laszlo] Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1089 Budapest, Hungary.
   [Szenasi, Gabor] Semmelweis Univ, Inst Translat Med, H-1089 Budapest, Hungary.
   [Zelles, Tibor; Koles, Laszlo] Semmelweis Univ, Dept Oral Biol, H-1089 Budapest, Hungary.
C3 Semmelweis University; Semmelweis University; Semmelweis University
RP Harsing, LG (通讯作者)，Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1089 Budapest, Hungary.
EM harsing.laszlo@med.semmelweis-univ.hu;
   szenasi.gabor@med.semmelweis-univ.hu;
   zelles.tibor@med.semmelweis-univ.hu; koles.laszlo@med.semmelweis-univ.hu
RI Szenasi, Gabor/ABH-2591-2021; Szénási, Gábor/K-3136-2017; Zelles,
   Tibor/J-9185-2017
OI Szénási, Gábor/0000-0002-7350-6091; Zelles, Tibor/0000-0002-0357-0469
FU Higher Education Institutional Excellence Program of the Ministry of
   Human Capacities in Hungary
FX This research was funded by the Higher Education Institutional
   Excellence Program of the Ministry of Human Capacities in Hungary,
   within the framework of the Neurology thematic program of Semmelweis
   University (FIKP 2020).
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NR 114
TC 3
Z9 3
U1 1
U2 5
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
PY 2021
VL 22
IS 12
AR 6209
DI 10.3390/ijms22126209
PG 22
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA SY7EM
UT WOS:000666046600001
PM 34201404
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Leung, HH
   Ng, ALK
   Durand, T
   Kawasaki, R
   Oger, C
   Balas, L
   Galano, JM
   Wong, IYH
   Lee, JCY
AF Leung, Ho Hang
   Ng, Alex L. K.
   Durand, Thierry
   Kawasaki, Ryo
   Oger, Camille
   Balas, Laurence
   Galano, Jean-Marie
   Wong, Ian Y. H.
   Lee, Jetty Chung-Yung
TI Increase in omega-6 and decrease in omega-3 polyunsaturated fatty acid
   oxidation elevates the risk of exudative AMD development in adults with
   Chinese diet
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Macular degeneration; Omega-6/omega-3 polyunsaturated fatty acid ratio;
   Carotenoids; Lipid peroxidation; Isoprostanes; Neuroprostanes; 4-HNE
ID MACULAR DEGENERATION; OXYGENATED METABOLITES; ARACHIDONIC-ACID;
   PATHOGENESIS; STRESS; BIOMARKERS; PRODUCTS; 8-HYDROXY-2'-DEOXYGUANOSINE;
   QUANTITATION; SYSTEM
AB Appropriate diet is essential for the regulation of age-related macular degeneration (AMD). In particular the type of dietary polyunsaturated fatty acids (PUFA) and poor antioxidant status including carotenoid levels concomitantly contribute to AMD risk. Build-up of oxidative stress in AMD induces PUFA oxidation, and a mix of lipid oxidation products (LOPs) are generated. However, LOPs are not comprehensively evaluated in AMD. LOPs are considered biomarkers of oxidative stress but also contributes to inflammatory response. In this cross-sectional case-control study, plasma omega-6/omega-3 PUFA ratios and antioxidant status (glutathione, superoxide dismutase and catalase), and plasma and urinary LOPs (41 types) were determined to evaluate its odds-ratio in the risk of developing exudative AMD (n = 99) compared to age-gender-matched healthy controls (n = 198) in adults with Chinese diet. The odds ratio of developing exudative AMD increased with LOPs from omega-6 PUFA and decreased from those of omega-3 PUFA. These observations were associated with a high plasma omega-6/omega-3 PUFA ratio and low carotenoid levels. In short, poor PUFA and antioxidant status increased the production of omega-6 PUFA LOPs such as dihomo-isoprostane and dihomo-isofuran, and lowered omega-3 PUFA LOPs such as neuroprostanes due to the high omega-6/omega-3 PUFA ratios; they were also correlated to the risk of AMD development. These findings indicate the generation of specific LOPs is associated with the development of exudative AMD.
C1 [Leung, Ho Hang; Lee, Jetty Chung-Yung] Univ Hong Kong, Sch Biol Sci, Pokfulam Rd, Hong Kong, Peoples R China.
   [Ng, Alex L. K.; Wong, Ian Y. H.] Univ Hong Kong, LKS Fac Med, Dept Ophthalmol, Hong Kong, Peoples R China.
   [Ng, Alex L. K.] Hong Kong Ophthalm Associates, Hong Kong, Peoples R China.
   [Durand, Thierry; Oger, Camille; Balas, Laurence; Galano, Jean-Marie] Univ Montpellier, CNRS, Inst Biomol Max Mousseron, ENSCM,UMR 5247, Montpellier, France.
   [Kawasaki, Ryo] Osaka Univ, Dept Vis Informat, Osaka, Japan.
   [Wong, Ian Y. H.] Hong Kong Sanat & Hosp, Dept Ophthalmol, Hong Kong, Peoples R China.
C3 University of Hong Kong; University of Hong Kong; Centre National de la
   Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC);
   Ecole nationale superieure de chimie de Montpellier; Universite de
   Montpellier; Osaka University
RP Lee, JCY (通讯作者)，Univ Hong Kong, Sch Biol Sci, Pokfulam Rd, Hong Kong, Peoples R China.; Wong, IYH (通讯作者)，Univ Hong Kong, LKS Fac Med, Dept Ophthalmol, Hong Kong, Peoples R China.; Wong, IYH (通讯作者)，Hong Kong Sanat & Hosp, Dept Ophthalmol, Hong Kong, Peoples R China.
EM jettylee@hku.hk
RI Lee, Jetty Chung-Yung/S-1443-2019; Kawasaki, Ryo/B-7266-2009; Lee, Jetty
   Chung-Yung/E-1475-2011
OI Lee, Jetty Chung-Yung/0000-0002-8175-7069; Kawasaki,
   Ryo/0000-0002-7492-6303; Lee, Jetty Chung-Yung/0000-0002-8175-7069;
   Camille, OGER/0000-0002-5177-5792
FU Health and Medical Research Fund [13142301]; Food and Health Bureau,
   Hong Kong
FX This work was supported by Health and Medical Research Fund (Ref:
   13142301), Food and Health Bureau, Hong Kong.
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NR 50
TC 9
Z9 9
U1 4
U2 12
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 2019
VL 145
BP 349
EP 356
DI 10.1016/j.freeradbiomed.2019.10.007
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA JK8OX
UT WOS:000495100700031
PM 31605749
OA Green Published
DA 2022-11-30
ER

PT J
AU Morrice, E
   Johnson, AP
   Marinier, JA
   Wittich, W
AF Morrice, E.
   Johnson, A. P.
   Marinier, J-A
   Wittich, W.
TI Assessment of the Apple iPad as a low-vision reading aid
SO EYE
LA English
DT Article
ID MACULAR DEGENERATION; PSYCHOPHYSICS; SPEED; REHABILITATION; PERFORMANCE;
   TECHNOLOGY; IMPAIRMENT; PROGRAM; READER; TEXT
AB Purpose Low- vision clients frequently report having problems with reading. Using magnification, reading performance (as measured by reading speed) can be improved by up to 200%. Current magnification aids can be expensive or bulky; therefore, we explored if the Apple iPad offers comparable performance in improving reading speeds, in comparison with a closedcircuit television (CCTV) video magnifier, or other magnification devices.
   Methods We recruited 100 participants between the ages of 24-97 years, with low vision who were literate and cognitively capable, of whom 57 had age-related macular degeneration. To assess reading, participants read standardized iReST texts and were tested for comprehension. We compared reading speed on the Apple iPad (10 inch) with that of the CCTV, home magnification devices, and baseline measures.
   Results All assistive devices improved reading rates in comparison to baseline (P<0.001, Hedge's g>1), however, there was no difference in improvement across devices (P>0.05, Hedge's g<0.1). When experience was taken into account, those with iPad experience read, on average, 30 words per minute faster than first time iPad users, whereas CCTV experience did not influence reading speed.
   Conclusions In our sample, the Apple iPad was as effective as currently used technologies for improving reading rates. Moreover, exposure to, and experience with the Apple iPad might increase reading speed with that device. A larger sample size, however, is needed to do subgroup analysis on who would optimally benefit from each type of magnification device.
C1 [Morrice, E.; Johnson, A. P.; Wittich, W.] Concordia Univ, Dept Psychol, 7141 Sherbrooke Ouest, Montreal, PQ H4B 1R6, Canada.
   [Morrice, E.; Johnson, A. P.; Marinier, J-A; Wittich, W.] Ctr Rech Interdisciplinaire Readaptat Montreal Me, Montreal, PQ, Canada.
   [Johnson, A. P.; Wittich, W.] Ctr Ouest Ile Montreal, CIUSSS, MAB Mackay, Ctr Readaptat, Montreal, PQ, Canada.
   [Marinier, J-A; Wittich, W.] Univ Montreal, Sch Optometry, Montreal, PQ, Canada.
C3 Concordia University - Canada; Universite de Montreal; Universite de
   Montreal
RP Morrice, E (通讯作者)，Concordia Univ, Dept Psychol, 7141 Sherbrooke Ouest, Montreal, PQ H4B 1R6, Canada.
EM elliott.morrice@mail.concordia.ca
RI Wittich, Walter/AAH-2145-2020
OI Wittich, Walter/0000-0003-2184-6139; Johnson, Aaron/0000-0002-4428-7109
FU Vision Research Network; Fonds de recherche du Quebec - Sante [28881,
   30620, 32643]; Antoine Turmel Foundation; MAB-Mackay Foundation
FX This work was supported in part by the Vision Research Network, the
   Fonds de recherche du Quebec - Sante (#28881, #30620, and #32643), the
   Antoine Turmel Foundation and the MAB-Mackay Foundation.
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NR 29
TC 27
Z9 27
U1 1
U2 15
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 2017
VL 31
IS 6
BP 865
EP 871
DI 10.1038/eye.2016.309
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EX2ON
UT WOS:000403066000006
PM 28157222
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Yang, P
   Skiba, NP
   Tewkesbury, GM
   Treboschi, VM
   Baciu, P
   Jaffe, GJ
AF Yang, Ping
   Skiba, Nikolai P.
   Tewkesbury, Grace M.
   Treboschi, Victoria M.
   Baciu, Peter
   Jaffe, Glenn J.
TI Complement-Mediated Regulation of Apolipoprotein E in Cultured Human RPE
   Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE AMD; RPE; complement; ApoE
ID MEMBRANE ATTACK COMPLEX; PIGMENT EPITHELIAL-CELLS; MACULAR-DEGENERATION;
   DRUSEN FORMATION; AGE; ACTIVATION; LIPOPROTEIN; PATHWAY; PROTEIN;
   EXPRESSION
AB Purpose. Complement activation is implicated in the pathogenesis of age-related macular degeneration (AMD). Apolipoprotein E (ApoE) and complement activation products such as membrane attack complex (MAC) are present in eyes of individuals with AMD. Herein, we investigated the effect of complement activation on induction of ApoE accumulation in human retinal pigment epithelial (RPE) cells.
   Methods. Cultured human RPE cells were primed with a complement-fixing antibody followed by treatment with C1q-depleted (C1q-Dep) human serum to elicit alternative pathway complement activation. Controls included anti-C5 antibody-treated serum and heat-inactivated C1q-Dep. Total protein was determined on RPE cell extracts, conditioned media, and extracellular matrix (ECM) by Western blot. ApoE and MAC colocalization was assessed on cultured RPE cells and human eyes by immunofluorescent stain. ApoE mRNA expression was evaluated by quantitative PCR (qPCR).
   Results. Complement challenge upregulated cell-associated ApoE, but not apolipoprotein A1. ApoE accumulation was blocked by anti-C5 antibody and enhanced by repetitive complement challenge. ApoE mRNA levels were not affected by complement challenge. ApoE was frequently colocalized with MAC in complement-treated cells and drusen from human eyes. ApoE was released into complement-treated conditioned media after a single complement challenge and accumulated on ECM after repetitive complement challenge.
   Conclusions. Complement challenge induces time-dependent ApoE accumulation in RPE cells. An understanding of the mechanisms by which complement affects RPE ApoE accumulation may help to better explain drusen composition, and provide insights into potential therapeutic targets.
C1 [Yang, Ping; Skiba, Nikolai P.; Tewkesbury, Grace M.; Treboschi, Victoria M.; Jaffe, Glenn J.] Duke Univ, Med Ctr, Dept Ophthalmol, 2351 Erwin Rd, Durham, NC 27710 USA.
   [Baciu, Peter] Allergan Pharmaceut Inc, Dept Biol, Irvine, CA USA.
C3 Duke University; AbbVie; Allergan
RP Jaffe, GJ (通讯作者)，Duke Univ, Med Ctr, Dept Ophthalmol, 2351 Erwin Rd, Durham, NC 27710 USA.
EM jaffe001@mc.duke.edu
OI Tewkesbury, Grace/0000-0001-7519-7731
FU National Institutes of Health [5P30EY005722]; Research to Prevent
   Blindness; NATIONAL EYE INSTITUTE [P30EY005722] Funding Source: NIH
   RePORTER
FX Supported, in part, by National Institutes of Health 5P30EY005722 (Core
   Grant) and Research to Prevent Blindness.
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NR 72
TC 16
Z9 17
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 JUN
PY 2017
VL 58
IS 7
BP 3073
EP 3085
DI 10.1167/iovs.16-20083
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EZ8FE
UT WOS:000404959300030
PM 28632844
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Nagai, N
   Ju, MH
   Izumi-Nagai, K
   Robbie, SJ
   Bainbridge, JW
   Gale, DC
   Pierre, E
   Krauss, AHP
   Adamson, P
   Shima, DT
   Ng, YS
AF Nagai, Nori
   Ju, Meihua
   Izumi-Nagai, Kanako
   Robbie, Scott J.
   Bainbridge, James W.
   Gale, David C.
   Pierre, Esaie
   Krauss, Achim H. P.
   Adamson, Peter
   Shima, David T.
   Ng, Yin-Shan
TI Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of
   Choroidal Neovascular Growth and Vascular Permeability
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; SYSTEMIC ABSORPTION; VEGF-A; RANIBIZUMAB;
   DELIVERY; EOTAXIN; TARGET
AB Choroidal neovascularization (CNV) is a defining feature of wet age-related macular degeneration. We examined the functional role of CCR3 in the development of CNV in mice and primates. CCR3 was associated with spontaneous CNV lesions in the newly described JR5558 mice, whereas CCR3 Ligands localized to CNV-associated macrophages and the retinal pigment epithelium/choroid complex. Intravitreal injection of neutralizing antibodies against vascular endothelial growth factor receptor 2, CCR3, CC chemokine Ligand 11/eotaxin-1, and CC chemokine Ligand 24/eotaxin-2 all reduced CNV area and Lesion number in these mice. Systemic administration of the CCR3 antagonists GW766994X and GW782415X reduced spontaneous CNV in JR5558 mice and laser-induced CNV in mouse and primate models in a dose-dependent fashion. Combination treatment with antivascular endothelial growth factor receptor 2 antibody and GW766994X yielded additive reductions in CNV area and hyperpermeability in mice. Interestingly, topical GW766994X and intravitreal anti-CCR3 antibody yielded strong systemic effects, reducing CNV in the untreated, contralateral eye. Contrarily, ocular administration of GW782415X in primates failed to substantially elevate plasma drug levels or to reduce the development of grade IV CNV lesions. These findings suggest that CCR3 signaling may be an attractive therapeutic target for CNV, utilizing a pathway that is at Least partly distinct from that of vascular endothelial growth factor receptor. The findings also demonstrate that systemic exposure to CCR3 antagonists may be crucial for CNV-targeted activity.
C1 [Nagai, Nori; Ju, Meihua; Izumi-Nagai, Kanako; Adamson, Peter; Shima, David T.; Ng, Yin-Shan] UCL, Inst Ophthalmol, Dept Ocular Biol & Therapeut, London, England.
   [Robbie, Scott J.; Bainbridge, James W.] UCL, Inst Ophthalmol, Dept Genet, London, England.
   [Gale, David C.; Adamson, Peter] GlaxoSmithKline, Ophthiris Discovery Performance Unit, Stevenage, Herts, England.
   [Pierre, Esaie] GlaxoSmithKline, Dept Drug Metab & Pharmacokinet, King Of Prussia, PA USA.
   [Krauss, Achim H. P.] GlaxoSmithKline, Ophthiris Discovery Performance Unit, King Of Prussia, PA USA.
C3 University of London; University College London; University of London;
   University College London; GlaxoSmithKline; GlaxoSmithKline;
   GlaxoSmithKline
RP Ng, YS (通讯作者)，Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM eric_ng@meei.harvard.edu
OI Bainbridge, James/0000-0003-1318-8201; Ng, Yin Shan/0000-0002-4982-1999
FU Medical Research Council [00800946]; National Eye Institute [EY019943];
   GlaxoSmithKline; Industrial Collaboration Grant to the University
   College London Institute of Ophthalmology; Wellcome Trust
   [099173/Z/12/Z]; NATIONAL EYE INSTITUTE [R01EY019943] Funding Source:
   NIH RePORTER; MRC [G0800946] Funding Source: UKRI; Medical Research
   Council [G0800946] Funding Source: researchfish; National Institute for
   Health Research [NIHR-RP-011-003] Funding Source: researchfish
FX Supported by an Industrial Collaboration Grant to the University College
   London Institute of Ophthalmology, Wellcome Trust grant 099173/Z/12/Z,
   Medical Research Council grant 00800946, National Eye Institute grant
   EY019943, and GlaxoSmithKline.
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NR 31
TC 20
Z9 20
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD SEP
PY 2015
VL 185
IS 9
BP 2534
EP 2549
DI 10.1016/j.ajpath.2015.04.029
PG 16
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA CR5ZB
UT WOS:000361421800018
PM 26188133
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Merle, NS
   Noe, R
   Halbwachs-Mecarelli, L
   Fremeaux-Bacchi, V
   Roumenina, LT
AF Merle, Nicolas S.
   Noe, Remi
   Halbwachs-Mecarelli, Lise
   Fremeaux-Bacchi, Veronique
   Roumenina, Lubka T.
TI Complement system part II: role in immunity
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE complement system; adaptive immunity; crosstalk TLR-complement; pathogen
   strategies for immune evasion; complement in cancer; complement and
   innate immunity; complement-related diseases; anaphylatoxins
ID HEMOLYTIC-UREMIC SYNDROME; DENSE DEPOSIT DISEASE; PAROXYSMAL-NOCTURNAL
   HEMOGLOBINURIA; FACTOR-H-AUTOANTIBODIES; MANNOSE-BINDING LECTIN; T-CELL
   RESPONSES; STAPHYLOCOCCUS-AUREUS PROTEIN; C3A ANAPHYLATOXIN RECEPTOR;
   DECAY-ACCELERATING FACTOR; ANTIGEN-SPECIFIC T
AB The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b-9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target.
C1 [Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.] INSERM, Ctr Rech Cordeliers, UMRS 1138, Paris, France.
   [Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.] Univ Paris 05, Sorbonne Paris Cite, Ctr Rech Cordeliers, UMRS 1138, Paris, France.
   [Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.] Univ Paris 06, Sorbonne Univ, Ctr Rech Cordeliers, UMRS 1138, Paris, France.
   [Noe, Remi] EPHE, Paris, France.
   [Fremeaux-Bacchi, Veronique] Hop Europeen Georges Pompidou, AP HP, Serv Immunol Biol, Paris, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Sorbonne Universite; Universite
   Paris Cite; Institut National de la Sante et de la Recherche Medicale
   (Inserm); UDICE-French Research Universities; Sorbonne Universite;
   Universite Paris Cite; Institut National de la Sante et de la Recherche
   Medicale (Inserm); UDICE-French Research Universities; Sorbonne
   Universite; Universite Paris Cite; UDICE-French Research Universities;
   PSL Research University Paris; Ecole Pratique des Hautes Etudes (EPHE);
   Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire
   Europeen Georges-Pompidou - APHP; UDICE-French Research Universities;
   Universite Paris Cite
RP Roumenina, LT (通讯作者)，Ctr Rech Cordeliers, 15 Rue Ecole Med, Paris, France.
EM lubka.roumenina@crc.jussieu.fr
RI Roumenina, Lubka/P-5906-2019; Roumenina, Lubka/L-2638-2017
OI Roumenina, Lubka/0000-0002-9940-0324; Noe, Remi/0000-0003-3474-4035
FU SIRIC-CARPEM; ARC [PJA 20141201954]; ANR Genopath [09geno031011];
   APHP-PHRC [AOM08198]; EU FP7 grant [2012-305608]; INSERM
FX This work was supported by grants from: SIRIC-CARPEM and ARC no. PJA
   20141201954 to LR and ANR Genopath 2009-2012 09geno031011, APHP-PHRC
   AOM08198 and EU FP7 grant 2012-305608 (EURenOmics) to VF-B and by
   INSERM. The shapes of the cells used in this review are inspired by
   http://smart.servier.fr/servier-medical-art.
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NR 282
TC 582
Z9 610
U1 17
U2 186
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 MAY 26
PY 2015
VL 6
AR 257
DI 10.3389/fimmu.2015.00257
PG 26
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA CJ2PL
UT WOS:000355326900001
PM 26074922
OA Green Published, Green Submitted, gold
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Kenney, MC
   Chwa, M
   Atilano, SR
   Falatoonzadeh, P
   Ramirez, C
   Malik, D
   Tarek, M
   Caceres-del-Carpio, J
   Nesburn, AB
   Boyer, DS
   Kuppermann, BD
   Vawter, M
   Jazwinski, SM
   Miceli, M
   Wallace, DC
   Udar, N
AF Kenney, M. Cristina
   Chwa, Marilyn
   Atilano, Shari R.
   Falatoonzadeh, Payam
   Ramirez, Claudio
   Malik, Deepika
   Tarek, Mohamed
   Caceres-del-Carpio, Javier
   Nesburn, Anthony B.
   Boyer, David S.
   Kuppermann, Baruch D.
   Vawter, Marquis
   Jazwinski, S. Michal
   Miceli, Michael
   Wallace, Douglas C.
   Udar, Nitin
TI Inherited mitochondrial DNA variants can affect complement, inflammation
   and apoptosis pathways: insights into mitochondrial-nuclear interactions
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID HEREDITARY OPTIC NEUROPATHY; FACTOR-H POLYMORPHISM; GROWTH-FACTOR-ALPHA;
   GENE-EXPRESSION; MACULAR DEGENERATION; PROSTATE-CANCER; RISK;
   HAPLOGROUPS; IL-33; LIPOFUSCIN
AB Age-related macular degeneration (AMD) is the leading cause of vision loss in developed countries. While linked to genetic polymorphisms in the complement pathway, there are many individuals with high risk alleles that do not develop AMD, suggesting that other 'modifiers' may be involved. Mitochondrial (mt) haplogroups, defined by accumulations of specific mtDNA single nucleotide polymorphisms (SNPs) which represent population origins, may be one such modifier. J haplogroup has been associated with high risk for AMD while the H haplogroup is protective. It has been difficult to assign biological consequences for haplogroups so we created human ARPE-19 cybrids (cytoplasmic hybrids), which have identical nuclei but mitochondria of either J or H haplogroups, to investigate their effects upon bioenergetics and molecular pathways. J cybrids have altered bioenergetic profiles compared with H cybrids. Q-PCR analyses show significantly lower expression levels for seven respiratory complex genes encoded by mtDNA. J and H cybrids have significantly altered expression of eight nuclear genes of the alternative complement, inflammation and apoptosis pathways. Sequencing of the entire mtDNA was carried out for all the cybrids to identify haplogroup and non-haplogroup defining SNPs. mtDNA can mediate cellular bioenergetics and expression levels of nuclear genes related to complement, inflammation and apoptosis. Sequencing data suggest that observed effects are not due to rare mtDNA variants but rather the combination of SNPs representing the J versus H haplogroups. These findings represent a paradigm shift in our concepts of mt-nuclear interactions.
C1 [Kenney, M. Cristina; Chwa, Marilyn; Atilano, Shari R.; Falatoonzadeh, Payam; Ramirez, Claudio; Malik, Deepika; Tarek, Mohamed; Caceres-del-Carpio, Javier; Nesburn, Anthony B.; Kuppermann, Baruch D.; Udar, Nitin] Univ Calif Irvine, Gavin Herbert Eye Inst, Irvine, CA 92697 USA.
   [Kenney, M. Cristina] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA.
   [Vawter, Marquis] Univ Calif Irvine, Dept Psychiat & Human Behav, Funct Genom Lab, Irvine, CA 92697 USA.
   [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] Tulane Univ, Tulane Ctr Aging, New Orleans, LA 70118 USA.
   [Wallace, Douglas C.] Childrens Hosp Philadelphia, Ctr Mitochondrial & Epigen Med, Philadelphia, PA 19104 USA.
C3 University of California System; University of California Irvine;
   University of California System; University of California Irvine;
   University of California System; University of California Irvine; Cedars
   Sinai Medical Center; Retina Vitreous Associates Medical Group; Tulane
   University; University of Pennsylvania; Pennsylvania Medicine; Childrens
   Hospital of Philadelphia
RP Kenney, MC (通讯作者)，Univ Calif Irvine, Discovery Ctr Eye Res, Gavin Herbert Eye Inst, Hewitt Hall,Room 2028,843 Hlth Sci Rd, Irvine, CA 92697 USA.
EM mkenney@uci.edu
OI CACERES DEL CARPIO, JAVIER/0000-0001-5673-5709; Udar,
   Nitin/0000-0001-8533-9190; Moustafa, M. Tarek/0000-0003-4545-6012;
   Atilano, Shari/0000-0002-7729-7864
FU Discovery Eye Foundation; Guenther Foundation; Beckman Macular Research
   Initiative; Polly and Michael Smith Foundation; Max Factor Family
   Foundation; Skirball Foundation; Lincy Foundation; Iris and the B.
   Gerald Cantor Foundation; Research to Prevent Blindness; National
   Institute on Aging [AG006168]; NATIONAL INSTITUTE OF MENTAL HEALTH
   [R01MH085801] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGING
   [R01AG006168, R37AG006168] Funding Source: NIH RePORTER
FX This work was supported by the Discovery Eye Foundation, Guenther
   Foundation, Beckman Macular Research Initiative, Polly and Michael Smith
   Foundation, Max Factor Family Foundation, Skirball Foundation, Lincy
   Foundation, Iris and the B. Gerald Cantor Foundation, Challenge Grant
   from Research to Prevent Blindness and the National Institute on Aging
   (AG006168 to S.M.J.).
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NR 98
TC 77
Z9 81
U1 0
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL
PY 2014
VL 23
IS 13
BP 3537
EP 3551
DI 10.1093/hmg/ddu065
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AK0ST
UT WOS:000338126300016
PM 24584571
OA Green Published
DA 2022-11-30
ER

PT J
AU Perez, VL
   Saeed, AM
   Tan, Y
   Urbieta, M
   Cruz-Guilloty, F
AF Perez, V. L.
   Saeed, A. M.
   Tan, Y.
   Urbieta, M.
   Cruz-Guilloty, F.
TI The eye: A window to the soul of the immune system
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Allo-transplantation; Cornea; Retina; Inflammation; Oxidative stress
ID T-CELL RECRUITMENT; ANTI-RETINAL ANTIBODIES; FACTOR-H POLYMORPHISM;
   ANTERIOR-CHAMBER; MACULAR DEGENERATION; CHEMOKINE RECEPTORS; CORNEAL
   ALLOGRAFTS; HIGH-RESOLUTION; GRAFT FAILURE; RISK
AB The eye is considered as an immune privileged site, and with good reason. It has evolved a variety of molecular and cellular mechanisms that limit immune responses to preserve vision. For example, the cornea is mainly protected from autoimmunity by the lack of blood and lymphatic vessels, whereas the retina-blood barrier is maintained in an immunosuppressive state by the retinal pigment epithelium. However, there are several scenarios in which immune privilege is altered and the eye becomes susceptible to immune attack. In this review, we highlight the role of the immune system in two clinical conditions that affect the anterior and posterior segments of the eye: corneal transplantation and age-related macular degeneration. Interestingly, crosstalk between the innate and adaptive immune systems is critical in both acute and chronic inflammatory responses in the eye, with T cells playing a central role in combination with neutrophils and macrophages. In addition, we emphasize the advantage of using the eye as a model for in vivo longitudinal imaging of the immune system in action. Through this technique, it has been possible to identify functionally distinct intra-graft motility patterns of responding T cells, as well as the importance of chemokine signaling in situ for T cell activation. The detailed study of ocular autoimmunity could provide novel therapeutic strategies for blinding diseases while also providing more general information on acute versus chronic inflammation. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Perez, V. L.; Saeed, A. M.; Tan, Y.; Urbieta, M.; Cruz-Guilloty, F.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Lab Ocular Immunol & Transplantat, Miami, FL 33136 USA.
   [Perez, V. L.; Cruz-Guilloty, F.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA.
C3 Bascom Palmer Eye Institute; University of Miami; University of Miami
RP Perez, VL (通讯作者)，Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Ocular Surface Ctr, 1638 10th Ave NW, Miami, FL 33136 USA.
EM Vperez4@med.miami.edu
RI Perez, Victor L./AAY-8633-2020
FU National Eye Institute, National Institutes of Health [R01 EY018624-04];
   Edward N. &Della L Thome Memorial Foundation Bank of America N.A.;
   Trustee Award Program in Macular Degeneration Research (VLP), NIH
   [P30EY14801]; Research to Prevent Blindness; Sheila and David Fuente
   Graduate Program in Cancer Biology; Sylvester Comprehensive Cancer
   Center; NATIONAL EYE INSTITUTE [R01EY018624, P30EY014801] Funding
   Source: NIH RePORTER
FX This work was supported by the National Eye Institute, National
   Institutes of Health R01 EY018624-04 (VLP), The Edward N. &Della L Thome
   Memorial Foundation Bank of America N.A. Trustee Award Program in
   Macular Degeneration Research (VLP), NIH P30EY14801 (Center Grant),
   Research to Prevent Blindness (Unrestricted Grant to the Bascom Palmer
   Eye Institute). A.M.S. acknowledges partial support and assistance from
   the Sheila and David Fuente Graduate Program in Cancer Biology,
   Sylvester Comprehensive Cancer Center. FCG is a Howard Hughes Medical
   Institute Fellow of the Life Sciences Research Foundation.
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NR 67
TC 64
Z9 64
U1 0
U2 18
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
EI 1095-9157
J9 J AUTOIMMUN
JI J. Autoimmun.
PD SEP
PY 2013
VL 45
BP 7
EP 14
DI 10.1016/j.jaut.2013.06.011
PG 8
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 231WH
UT WOS:000325448600002
PM 23871641
DA 2022-11-30
ER

PT J
AU Yu, AL
   Birke, K
   Burger, J
   Welge-Lussen, U
AF Yu, Alice L.
   Birke, Kerstin
   Burger, Johannes
   Welge-Lussen, Ulrich
TI Biological Effects of Cigarette Smoke in Cultured Human Retinal Pigment
   Epithelial Cells
SO PLOS ONE
LA English
DT Article
ID HUMAN-DIPLOID FIBROBLASTS; CAUSES OXIDATIVE DAMAGE; GROWTH-FACTOR-BETA;
   MACULAR DEGENERATION; IN-VITRO; EXTRACELLULAR-MATRIX; GEOGRAPHIC
   ATROPHY; SENESCENCE; STRESS; EXPRESSION
AB The goal of the present study was to determine whether treatment with cigarette smoke extract (CSE) induces cell loss, cellular senescence, and extracellular matrix (ECM) synthesis in primary human retinal pigment epithelial (RPE) cells. Primary cultured human RPE cells were exposed to 2, 4, 8, and 12% of CSE concentration for 24 hours. Cell loss was detected by cell viability assay. Lipid peroxidation was assessed by loss of cis-parinaric acid (PNA) fluorescence. Senescence-associated beta-galactosidase (SA-beta-Gal) activity was detected by histochemical staining. Expression of apolipoprotein J (Apo J), connective tissue growth factor (CTGF), fibronectin, and laminin were examined by real-time PCR, western blot, or ELISA experiments. The results showed that exposure of cells to 12% of CSE concentration induced cell death, while treatment of cells with 2, 4, and 8% CSE increased lipid peroxidation. Exposure to 8% of CSE markedly increased the number of SA-beta-Gal positive cells to up to 82%, and the mRNA expression of Apo J, CTGF, and fibronectin by approximately 3-4 fold. Treatment with 8% of CSE also increased the protein expression of Apo J and CTGF and the secretion of fibronectin and laminin. Thus, treatment with CSE can induce cell loss, senescent changes, and ECM synthesis in primary human RPE cells. It may be speculated that cigarette smoke could be involved in cellular events in RPE cells as seen in age-related macular degeneration.
C1 [Yu, Alice L.; Burger, Johannes] Univ Muenchen, Dept Ophthalmol, Munich, Germany.
C3 University of Munich
RP Yu, AL (通讯作者)，Univ Muenchen, Dept Ophthalmol, Munich, Germany.
EM alice.yu@med.uni-muenchen.de
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NR 58
TC 19
Z9 19
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 NOV 14
PY 2012
VL 7
IS 11
AR e48501
DI 10.1371/journal.pone.0048501
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 038CD
UT WOS:000311151900020
PM 23155386
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Tarita-Nistor, L
   Brent, MH
   Steinbach, MJ
   Gonzalez, EG
AF Tarita-Nistor, Luminita
   Brent, Michael H.
   Steinbach, Martin J.
   Gonzalez, Esther G.
TI Fixation Patterns in Maculopathy: From Binocular to Monocular Viewing
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE fixation; PRL; age-related macular degeneration; central vision loss;
   ocular motor control; binocular viewing; monocular viewing
ID PREFERRED RETINAL LOCI; CENTRAL VISION LOSS; MACULAR DEGENERATION;
   SACCADIC INTRUSIONS; VISUAL IMPAIRMENT; EYE-MOVEMENTS; DISEASE;
   STABILITY; FOVEA; GAZE
AB Purpose. The goal of this study was to explore binocular coordination during fixation in patients with age-related macular degeneration (AMD) and to investigate whether there is a shift in eye position when the viewing condition changes from binocular to monocular.
   Methods. Sixteen people with normal vision and 12 patients with AMD were asked to look at a 3 deg fixation target with both eyes and with each eye individually while the fellow eye was covered by an infrared filter. Fixational eye movements were recorded for both eyes with an EyeLink eye-tracker in all conditions. The shift in eye position at the end of every fixation period was calculated for each eye.
   Results. All people with normal vision as well as the majority of patients had good binocular coordination during fixation in the binocular viewing condition. When the viewing condition changed from binocular to monocular, three patients (25%) had atypical shifts in their eye position. The shift was related to (1) loss of fixational control when the better eye was covered and the worse eye viewed the target or (2) a slow drift of the viewing eye that was associated with a large phoria in the covered eye.
   Conclusions. Patients with AMD have good binocular ocular motor coordination during fixation. A change in viewing condition from binocular to monocular can lead to disturbances in ocular motor control for some patients, especially in the worse eye. (Optom Vis Sci 2012;89:277-287)
C1 [Tarita-Nistor, Luminita; Brent, Michael H.; Steinbach, Martin J.; Gonzalez, Esther G.] Toronto Western Hosp, Vis Sci Res Program, Toronto, ON M5T 2S8, Canada.
   [Tarita-Nistor, Luminita; Steinbach, Martin J.; Gonzalez, Esther G.] York Univ, Ctr Vis Res, Toronto, ON M3J 2R7, Canada.
   [Tarita-Nistor, Luminita; Brent, Michael H.; Steinbach, Martin J.; Gonzalez, Esther G.] Univ Toronto, Dept Ophthalmol & Vis Sci, Toronto, ON, Canada.
C3 University of Toronto; University Toronto Affiliates; University Health
   Network Toronto; York University - Canada; University of Toronto
RP Gonzalez, EG (通讯作者)，Toronto Western Res Inst, Vis Sci Res Program, 399 Bathurst St,FP 6-212, Toronto, ON M5T 2S8, Canada.
EM gonzalez@yorku.ca
FU Milton Harris Fund for Adult Macular Degeneration; Natural Sciences and
   Engineering Research Council of Canada (NSERC) [A7664]; Toronto Western
   Hospital
FX This work was supported by the Milton Harris Fund for Adult Macular
   Degeneration (to MHB); Natural Sciences and Engineering Research Council
   of Canada (NSERC) grant A7664 (to MJS); Vision Science Research Program,
   Toronto Western Hospital; and an anonymous donor.
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NR 53
TC 18
Z9 19
U1 0
U2 11
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 MAR
PY 2012
VL 89
IS 3
BP 277
EP 287
DI 10.1097/OPX.0b013e318244e8b1
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 918FE
UT WOS:000302233900009
PM 22266814
DA 2022-11-30
ER

PT J
AU Yafai, Y
   Yang, XM
   Niemeyer, M
   Nishiwaki, A
   Lange, J
   Wiedemann, P
   King, AG
   Yasukawa, T
   Eichler, W
AF Yafai, Yousef
   Yang, Xiu Mei
   Niemeyer, Marc
   Nishiwaki, Akiko
   Lange, Johannes
   Wiedemann, Peter
   King, Andrew G.
   Yasukawa, Tsutomu
   Eichler, Wolfram
TI Anti-angiogenic effects of the receptor tyrosine kinase inhibitor,
   pazopanib, on choroidal neovascularization in rats
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE Receptor tyrosine kinase inhibitor; VEGF [vascular endothelial growth
   factor]; Age-related macular degeneration; Choroidal neovascularization;
   Angiogenesis; Pazopanib
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; TUMOR ANGIOGENESIS;
   FACTOR EXPRESSION; VEGF; CELLS; RANIBIZUMAB; CYTOKINES
AB Neovascularization in the eye is a major cause of irreversible vision loss. The present study was undertaken to determine mechanisms through which pazopanib, a drug that targets multiple receptor tyrosine kinases such as VEGF receptors, inhibits angiogenesis and experimental choroidal neovascularization (CNV). Pazopanib inhibited VEGF expression by retinal pigment epithelium (RPE) cells and choroidal endothelial cells (CEC), decreased VEGF-induced cellular migration in a dose-dependent manner and suppressed extracellular signal-regulated kinase (ERK)-1/-2 phosphorylation. To assess the impact of pazopanib in vivo, CNV was induced in rats by rupturing the Bruch's membrane by laser coagulation. These experiments demonstrated that twice-daily topical eye drop treatment significantly (P<0.001) decreased leakage from photocoagulated lesions by 89.5%. Furthermore, the thickness of the developed CNV lesions was significantly inhibited by 71.7% (P<0.001) in pazopanib-treated eyes, and immunoreactivity of VEGF was lower than in control eyes. Our data suggest that pazopanib is a promising inhibitor of angiogenesis leading to an effective inhibition of CNV development in vivo. This activity can be largely ascribed to the down-regulation of VEGF release in the retina as well as to impaired VEGF-induced signaling and chemotaxis. Using a convenient topical dosing regimen, pazopanib may prove useful for treating a variety of ocular neovascular diseases such as neovascular age-related macular degeneration. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Yafai, Yousef; Yang, Xiu Mei; Niemeyer, Marc; Nishiwaki, Akiko; Lange, Johannes; Wiedemann, Peter; Yasukawa, Tsutomu; Eichler, Wolfram] Univ Leipzig, Hosp Eye, D-04103 Leipzig, Germany.
   [Yafai, Yousef; Yang, Xiu Mei; Niemeyer, Marc; Nishiwaki, Akiko; Lange, Johannes; Wiedemann, Peter; Yasukawa, Tsutomu; Eichler, Wolfram] Univ Leipzig, Dept Ophthalmol, D-04103 Leipzig, Germany.
   [Yang, Xiu Mei] Fourth Mil Med Univ, Xijing Hosp, Eye Inst Ophthalmol Chinese PLA, Dept Ophthalmol, Xian 710032, Shaanxi Prov, Peoples R China.
   [Nishiwaki, Akiko; Yasukawa, Tsutomu] Nagoya City Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med Sci, Nagoya, Aichi, Japan.
   [King, Andrew G.] GlaxoSmithKline Inc, Dept Translat Res, King Of Prussia, PA 19406 USA.
C3 Leipzig University; Leipzig University; Air Force Military Medical
   University; Nagoya City University; GlaxoSmithKline
RP Eichler, W (通讯作者)，Univ Leipzig, Hosp Eye, Liebigstr 10-14, D-04103 Leipzig, Germany.
EM eichwolf@rz.uni-leipzig.de
RI Yang, XM/AAM-9762-2020; ma, qi/G-3268-2011
FU GlaxoSmithKline; Interneuro Graduate College Leipzig; Deutsche
   Forschungsgemeinschaft [RE 849/14-1, GRK 1097/1-1]; Ernst und Berta
   Grimmke Stiftung, Dusseldorf, Germany; Interdisciplinary Centre for
   Clinical Research at the University of Leipzig [01KS9504, C5]
FX This work was supported by GlaxoSmithKline. X.M.Y. and J. L. were
   supported by a grant of the Interneuro Graduate College Leipzig. The
   study was also supported by Deutsche Forschungsgemeinschaft (RE 849/14-1
   and GRK 1097/1-1), Ernst und Berta Grimmke Stiftung, Dusseldorf,
   Germany, and Interdisciplinary Centre for Clinical Research at the
   University of Leipzig (01KS9504, Project C5).
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NR 32
TC 31
Z9 36
U1 1
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD SEP
PY 2011
VL 666
IS 1-3
BP 12
EP 18
DI 10.1016/j.ejphar.2011.05.016
PG 7
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 796KT
UT WOS:000293050900003
PM 21620822
DA 2022-11-30
ER

PT J
AU Nolan, JM
   Kenny, R
   O'Regan, C
   Cronin, H
   Loughman, J
   Connolly, EE
   Kearney, P
   Loane, E
   Beatty, S
AF Nolan, John M.
   Kenny, Roseanne
   O'Regan, Claire
   Cronin, Hilary
   Loughman, James
   Connolly, Eithne E.
   Kearney, Patricia
   Loane, Edward
   Beatty, Stephen
TI Macular Pigment Optical Density in an Ageing Irish Population: The Irish
   Longitudinal Study on Ageing
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Irish Longitudinal Study on Ageing;
   Macular pigment optical density
ID AGE-RELATED MACULOPATHY; HETEROCHROMATIC FLICKER PHOTOMETRY; BEAVER DAM
   EYE; SERUM CONCENTRATIONS; CONSTITUENT CAROTENOIDS; RAMAN MEASUREMENT;
   DEGENERATION; ZEAXANTHIN; LUTEIN; REFLECTOMETRY
AB Purpose: The 3 carotenoids lutein, zeaxanthin, and meso-zeaxanthin, which account for the 'yellow spot' at the macula and which are referred to as macular pigment (MP), are believed to play a role in visual function and protect against age-related macular degeneration (AMD) via their optical and antioxidant properties. This study was undertaken to compare MP optical density (MPOD) in a population aged >= 50 years with MPOD values from a normative database of subjects aged 18-60 years. Methods: Seventy-nine subjects were recruited into this pilot study (The Irish Longitudinal Study on Ageing-TILDA). MPOD was measured using heterochromatic flicker photometry. Retinal fundus photographs, lifestyle data and general health data, were also obtained. Results: The mean +/- SD age of the 79 subjects recruited into this study was 65 +/- 11 years. There was a moderate, but statistically significant, age-related decline in MPOD at 0.5 degrees in the TILDA data (r = -0.251, p = 0.045), which remained upon merging with a normative database of an additional 462 subjects aged between 18 and 67 years (r = -0.179, p = 0.000). Conclusions: We report an inverse association between MPOD and increasing age. Longitudinal data in a larger cohort of participants are required to satisfactorily investigate the relationship between the optical density of this pigment and age, and with risk for development and/or progression of AMD. This pilot study represents a first step in this endeavour. Copyright (C) 2010 S. Karger AG, Basel
C1 [Nolan, John M.; Connolly, Eithne E.; Loane, Edward; Beatty, Stephen] Waterford Inst Technol, Macular Pigment Res Grp, Dept Chem & Life Sci, Waterford, Ireland.
   [Nolan, John M.; Connolly, Eithne E.; Beatty, Stephen] Whitfield Clin, Inst Vis Res, Waterford, Ireland.
   [Kenny, Roseanne; O'Regan, Claire; Cronin, Hilary; Kearney, Patricia] Univ Dublin, TILDA Res Grp, Dublin, Ireland.
   [Loughman, James] Dublin Inst Technol, Dept Optometry, Macular Pigment Res Grp, Dublin, Ireland.
C3 South East Technological University (SETU); Technological University
   Dublin
RP Nolan, JM (通讯作者)，Waterford Inst Technol, Macular Pigment Res Grp, Dept Chem & Life Sci, Waterford, Ireland.
EM jmnolan@wit.ie
RI Kearney, Patricia M/AAE-8501-2020; Nolan, John/N-4921-2014
OI Kearney, Patricia/0000-0001-9599-3540; Loughman,
   James/0000-0003-3130-8991; Nolan, John/0000-0002-5503-7084
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NR 58
TC 38
Z9 38
U1 0
U2 8
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2010
VL 44
IS 2
BP 131
EP 139
DI 10.1159/000315531
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 633QS
UT WOS:000280519600006
PM 20516725
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Yang, Z
   Kitsos, G
   Tong, Z
   Payne, M
   Gorezis, S
   Psilas, K
   Grigoriadou, M
   Zhao, Y
   Kamaya, S
   Aperis, G
   Petersen, MB
   Zhang, K
AF Yang, Z.
   Kitsos, G.
   Tong, Z.
   Payne, M.
   Gorezis, S.
   Psilas, K.
   Grigoriadou, M.
   Zhao, Y.
   Kamaya, S.
   Aperis, G.
   Petersen, M. B.
   Zhang, K.
TI A novel locus on 19q13 associated with autosomal-dominant macular
   dystrophy in a large Greek family
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID AREOLAR CHOROIDAL DYSTROPHY; MULTILOCUS LINKAGE ANALYSIS; SORSBYS FUNDUS
   DYSTROPHY; CONE-ROD DYSTROPHY; CHROMOSOME 6Q; PERIPHERIN/RDS GENE; RDS
   GENE; MAPS; LOCALIZATION; MUTATION
AB Objective: To describe the clinical features of and genetic locus associated with autosomal-dominant macular dystrophy (MCDR5) in a large Greek family.
   Methods: 26 members of a single family underwent clinical examinations and venepuncture. A genomewide linkage scan using 400 microsatellite markers distributed with an average spacing of 10 cM throughout the human genome.
   Results: 14 members of the study family exhibited clinical features of the disease including decreased central vision and macular abnormalities in the posterior pole of the retina. Analysis of loci known to be associated with macular dystrophy did not show positive linkage. A genomewide linkage scan showed linkage to chromosome 19q, with a two-point maximum LOD score of 5.809 at theta = 0 between the disease and marker locus D19S412. On the basis of recombination events, the disease interval was localised between markers D19S420 and D19S540 on chromosome 19q, at a span of about 3.8 cM, in an area known to contain 120 known genes/transcripts. Eleven of these genes/transcripts were sequenced, and no disease-causing mutation was identified.
   Conclusions: This study describes a new locus on 19q associated with autosomal-dominant macular dystrophy, designated as MCDR5. Additional study of other family members will be necessary to further narrow the interval and identify the responsible gene. The study of MCDR5 will aid in elucidation of the underlying pathogenic mechanisms for this and other macular diseases, including age-related macular degeneration.
C1 Univ Utah, Hlth Sci Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA.
   Univ Utah, Hlth Sci Ctr, Program Human Mol Biol & Genet, Eccles Inst Human Genet, Salt Lake City, UT 84132 USA.
   Univ Ioannina, Dept Ophthalmol, GR-45110 Ioannina, Greece.
   Inst Child Hlth, Dept Genet, Athens, Greece.
C3 Utah System of Higher Education; University of Utah; Utah System of
   Higher Education; University of Utah; University of Ioannina
RP Yang, Z (通讯作者)，Univ Utah, Hlth Sci Ctr, Dept Ophthalmol & Visual Sci, 15 N 2030 E,Bldg 533,Rm 3060A, Salt Lake City, UT 84132 USA.
EM kang.zhang@hmbg.utah.edu
RI Zhang, Kang/Y-2740-2019; Petersen, Michael Bjørn B/D-1483-2017
OI Zhang, Kang/0000-0002-4549-1697; Petersen, Michael Bjørn
   B/0000-0003-0316-8207
FU NEI NIH HHS [R01 EY014428, R01 EY014448, R01 EY14428, R01 EY14448]
   Funding Source: Medline; NATIONAL EYE INSTITUTE [R01EY014428,
   R01EY014448] Funding Source: NIH RePORTER
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NR 30
TC 3
Z9 3
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD DEC
PY 2006
VL 43
IS 12
AR e57
DI 10.1136/jmg.2005.040188
PG 4
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 111VR
UT WOS:000242483900012
PM 17142619
OA Green Published
DA 2022-11-30
ER

PT J
AU Kasindi, A
   Fuchs, DT
   Koronyo, Y
   Rentsendorj, A
   Black, KL
   Koronyo-Hamaoui, M
AF Kasindi, Arielle
   Fuchs, Dieu-Trang
   Koronyo, Yosef
   Rentsendorj, Altan
   Black, Keith L.
   Koronyo-Hamaoui, Maya
TI Glatiramer Acetate Immunomodulation: Evidence of Neuroprotection and
   Cognitive Preservation
SO CELLS
LA English
DT Review
DE Copolymer-1 (Cop-1); glaucoma; Parkinson's disease; Huntington's
   disease; experimental autoimmune encephalomyelitis; AD; retinal
   inflammation; optic neuropathy; cerebral ischemia; neuropsychology
ID REMITTING MULTIPLE-SCLEROSIS; QUALITY-OF-LIFE; CHRONIC CEREBRAL
   HYPOPERFUSION; TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; ANIMAL-MODEL;
   NEUROTROPHIC FACTOR; INTERFERON-BETA; T-CELLS; HUNTINGTONS-DISEASE
AB Novel, neuroprotective uses of Copaxone (generic name: glatiramer acetate-GA) are being examined, primarily in neurological conditions involving cognitive decline. GA is a well-studied synthetic copolymer that is FDA-approved for immune-based treatment of relapsing remitting multiple sclerosis (RRMS). Clinical studies have explored the potential mechanism of action (MOA) and outcomes of GA immunization in patients. Furthermore, results from these and animal studies suggest that GA has a direct immunomodulatory effect on adaptive and innate immune cell phenotypes and responses. These MOAs have been postulated to have a common neuroprotective impact in several neuroinflammatory and neurodegenerative diseases. Notably, several clinical studies report that the use of GA mitigated MS-associated cognitive decline. Its propensity to ameliorate neuro-proinflammatory and degenerative processes ignites increased interest in potential alternate uses such as in age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD). Preclinical studies are exploring less frequent subcutaneous administration of GA, such as once weekly or monthly or a single dosing regimen. Indeed, cognitive functions were found to be either preserved, reversed, or improved after the less frequent treatment regimens with GA in animal models of AD. In this systematic review, we examine the potential novel uses of GA across clinical and pre-clinical studies, with evidence for its beneficial impact on cognition. Future investigation in large-size, double-blind clinical trials is warranted to establish the impact of GA immunomodulation on neuroprotection and cognitive preservation in various neurological conditions.
C1 [Kasindi, Arielle; Fuchs, Dieu-Trang; Koronyo, Yosef; Rentsendorj, Altan; Black, Keith L.; Koronyo-Hamaoui, Maya] Cedars Sinai Med Ctr, Maxine Dunitz Neurosurg Inst, Dept Neurosurg, Los Angeles, CA 90048 USA.
   [Koronyo-Hamaoui, Maya] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA.
C3 Cedars Sinai Medical Center; Cedars Sinai Medical Center
RP Koronyo-Hamaoui, M (通讯作者)，Cedars Sinai Med Ctr, Maxine Dunitz Neurosurg Inst, Dept Neurosurg, Los Angeles, CA 90048 USA.; Koronyo-Hamaoui, M (通讯作者)，Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA.
EM arielle.kasindi@cshs.org; dieu-trang.fuchs@cshs.org;
   yosef.koronyo@cshs.org; altan.rentsendorj@cshs.org;
   keith.black@cshs.org; maya.koronyo@csmc.edu
RI Koronyo-Hamaoui, Maya/AAG-2040-2021
OI Koronyo-Hamaoui, Maya/0000-0003-2864-8442; Black,
   Keith/0000-0002-0546-4934; Kasindi, Arielle/0000-0002-6612-6357
FU National Institutes of Health (NIH) [NIA R01AG056478, NIA R01AG055865,
   AG056478-04S1]; Tom Gordon Private Foundation [CSR 20847]; Haim Saban
   Foundation [CSR 20847]
FX The authors acknowledge funding support from the National Institutes of
   Health (NIH) grant numbers NIA R01AG056478, NIA R01AG055865 and
   AG056478-04S1 (M.K.-H.). This work was also supported by The Haim Saban
   and The Tom Gordon Private Foundations (CSR 20847) (M.K.H.).
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NR 181
TC 1
Z9 1
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD MAY
PY 2022
VL 11
IS 9
AR 1578
DI 10.3390/cells11091578
PG 38
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 1E6BB
UT WOS:000794570300001
PM 35563884
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU George, SM
   Lu, FF
   Rao, M
   Leach, LL
   Gross, JM
AF George, Stephanie M.
   Lu, Fangfang
   Rao, Mishal
   Leach, Lyndsay L.
   Gross, Jeffrey M.
TI The retinal pigment epithelium: Development, injury responses, and
   regenerative potential in mammalian and non-mammalian systems
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Retinal pigment epithelium (RPE); Regeneration; Development; Age-related
   macular degeneration (AMD); Zebrafish
ID AGE-RELATED MACULOPATHY; PENETRATING EYE INJURY; CELL-BASED THERAPIES;
   MACULAR DEGENERATION; MULLER GLIA; MESENCHYMAL TRANSITION; IN-VIVO;
   STEM-CELL; INTERPHOTORECEPTOR MATRIX; OXIDATIVE STRESS
AB Diseases that result in retinal pigment epithelium (RPE) degeneration, such as age-related macular degeneration (AMD), are among the leading causes of blindness worldwide. Atrophic (dry) AMD is the most prevalent form of AMD and there are currently no effective therapies to prevent RPE cell death or restore RPE cells lost from AMD. An intriguing approach to treat AMD and other RPE degenerative diseases is to develop therapies focused on stimulating endogenous RPE regeneration. For this to become feasible, a deeper understanding of the mecha-nisms underlying RPE development, injury responses and regenerative potential is needed. In mammals, RPE regeneration is extremely limited; small lesions can be repaired by the expansion of adjacent RPE cells, but large lesions cannot be repaired as remaining RPE cells are unable to functionally replace lost RPE tissue. In some injury paradigms, RPE cells proliferate but do not regenerate a morphologically normal monolayer, while in others, proliferation is pathogenic and results in further disruption to the retina. This is in contrast to non -mammalian vertebrates, which possess tremendous RPE regenerative potential. Here, we discuss what is known about RPE formation during development in mammalian and non-mammalian vertebrates, we detail the processes by which RPE cells respond to injury, and we describe examples of RPE-to-retina and RPE-to-RPE regeneration in non-mammalian vertebrates. Finally, we outline barriers to RPE-dependent regeneration in mammals that could potentially be overcome to stimulate a regenerative response from the RPE.
C1 [George, Stephanie M.; Lu, Fangfang; Rao, Mishal; Leach, Lyndsay L.; Gross, Jeffrey M.] Univ Pittsburgh, Sch Med, Louis J Fox Ctr Vis Restorat, Dept Ophthalmol, Pittsburgh, PA 15213 USA.
   [Gross, Jeffrey M.] Univ Pittsburgh, Dept Dev Biol, Sch Med, Pittsburgh, PA 15213 USA.
   [Lu, Fangfang] Cent South Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha 410011, Hunan, Peoples R China.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; Pennsylvania Commonwealth System of Higher Education
   (PCSHE); University of Pittsburgh; Central South University
RP Gross, JM (通讯作者)，Univ Pittsburgh, Sch Med, Louis J Fox Ctr Vis Restorat, Dept Ophthalmol, Pittsburgh, PA 15213 USA.
EM grossjm@pitt.edu
OI George, Stephanie/0000-0001-9530-9737; Rao, Mishal/0000-0003-2044-682X;
   Gross, Jeffrey/0000-0002-9422-6312; Leach, Lyndsay/0000-0002-5138-1371
FU National Institutes of Health [T32-EY17271, RO1-EY29410]; NIH CORE
   [P30-EY08098]; Pennsylvania Lions Sight Conservation and Eye Research
   Foundation; Charles and Louella Snyder Retinal Regeneration Fund;
   Macular Degeneration Research Program of the BrightFocus Foundation
   [M2016067]; E. Ronald Salvitti Chair in Ophthalmology Research; Martha
   Wandrisco Neff Research Award in Macular Degeneration; Wiegand
   Fellowship in Ophthalmology; Honors College HEAL Research Fellowship;
   Eye & Ear Foundation of Pittsburgh; Research to Prevent Blindness, New
   York, NY
FX Research on RPE regeneration in J.M.G's laboratory is supported by the
   National Institutes of Health (T32-EY17271 to L.L.L., RO1-EY29410 to
   J.M.G, and NIH CORE Grant P30-EY08098 to the Department of
   Ophthalmology); the UPMC Immune Transplant & Therapy Center (to L. L.L.
   and J.M.G.); the Pennsylvania Lions Sight Conservation and Eye Research
   Foundation (to L.L.L. and J.M.G.); the Charles and Louella Snyder
   Retinal Regeneration Fund (to J.M.G.); the Macular Degeneration Research
   Program of the BrightFocus Foundation (M2016067 to J. M.G); and the E.
   Ronald Salvitti Chair in Ophthalmology Research (to J. M.G.). Additional
   support was received from the Martha Wandrisco Neff Research Award in
   Macular Degeneration (to L.L.L.), the Wiegand Fellowship in
   Ophthalmology (to L.L.L), an Honors College HEAL Research Fellowship (to
   S.M.G), the Eye & Ear Foundation of Pittsburgh, and an unrestricted
   grant from Research to Prevent Blindness, New York, NY. We also wish to
   thank Rachel Nagy for editorial assistance and Drs. Emeline Nandrot and
   Debasish Sinha for helpful comments on this manuscript.L.L.L. is
   co-inventor on a US Patent (#9,458,428) related to deriving RPE from
   pluripotent stem cells in vitro; while not directly related to the
   content herein, we wish to disclose this patent. All other authors
   declare no conflicts of interest.
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NR 342
TC 18
Z9 18
U1 3
U2 12
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 NOV
PY 2021
VL 85
AR 100969
DI 10.1016/j.preteyeres.2021.100969
EA NOV 2021
PG 25
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WZ7DH
UT WOS:000720124200001
PM 33901682
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zhang, AC
   Singh, S
   Craig, JP
   Downie, LE
AF Zhang, Alexis Ceecee
   Singh, Sumeer
   Craig, Jennifer P.
   Downie, Laura E.
TI Omega-3 Fatty Acids and Eye Health: Opinions and Self-Reported Practice
   Behaviors of Optometrists in Australia and New Zealand
SO NUTRIENTS
LA English
DT Article
DE omega-3; fatty acid; diet; supplement; optometrist; survey; nutrition;
   practice; eye disease; dry eye; age-related macular degeneration
ID ALPHA-LINOLENIC ACID; POLYUNSATURATED FATTY-ACIDS; MACULAR DEGENERATION;
   DOCOSAHEXAENOIC ACID; EICOSAPENTAENOIC ACID; CLINICAL-TRIAL; VITAMIN-C;
   OMEGA-3; DISEASE; SUPPLEMENTATION
AB This study investigated optometrists' attitudes and self-reported practice behaviors towards omega-3 fatty acids for eye health, and knowledge and understanding of their potential risks and benefits. An anonymous online survey was distributed to optometrists in Australia and New Zealand. Questions included practitioner demographics and practice modality; self-reported practices and recommendations relating to diet, nutritional supplements, and omega-3 fatty acids for age-related macular degeneration (AMD) and dry eye disease (DED); and practitioner knowledge about omega-3 fatty acids. Of 206 included surveys, most respondents (79%) indicated recommending for their patients to consume omega-3 fatty acids to improve their eye health. Sixty-eight percent of respondents indicated recommending omega-3-rich foods for AMD management, while 62% indicated recommending omega-3 supplements. Most respondents (78%) indicated recommending omega-3-rich foods or supplements for DED. For DED, recommended omega-3 supplement dosages were (median [inter-quartile range, IQR]) 2000 mg [1000-2750 mg] per day. The main sources of information reported by respondents to guide their clinical decision making were continuing education articles and conferences. In conclusion, optometrists routinely make clinical recommendations about diet and omega-3 fatty acids. Future education could target improving optometrists' knowledge of differences in the evidence for whole-food versus supplement sources of omega-3 fatty acids in AMD. Further research is needed to address uncertainties in the evidence regarding optimal omega-3 dosage and formulation composition in DED.
C1 [Zhang, Alexis Ceecee; Singh, Sumeer; Downie, Laura E.] Univ Melbourne, Dept Optometry & Vis Sci, Carlton, Vic 3053, Australia.
   [Craig, Jennifer P.] Univ Auckland, Dept Ophthalmol, New Zealand Natl Eye Ctr, Auckland 1023, New Zealand.
C3 University of Melbourne; University of Auckland
RP Downie, LE (通讯作者)，Univ Melbourne, Dept Optometry & Vis Sci, Carlton, Vic 3053, Australia.
EM alexisz@student.unimelb.edu.au; shari@student.unimelb.edu.au;
   jp.craig@auckland.ac.nz; ldownie@unimelb.edu.au
RI Craig, Jennifer P./S-9304-2019; Britten-Jones, Alexis
   Ceecee/AAJ-4295-2020
OI Britten-Jones, Alexis Ceecee/0000-0002-1101-2870; Singh,
   Sumeer/0000-0003-3519-7037; Downie, Laura/0000-0002-1596-2259
FU Australian Government Research Training Program Scholarship; Melbourne
   International Research Training Scholarship
FX This research received no external funding. A.C.Z. was supported by an
   Australian Government Research Training Program Scholarship for her PhD
   studies. S.S. was supported by a Melbourne International Research
   Training Scholarship for his PhD studies.
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TC 6
Z9 6
U1 1
U2 7
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-6643
J9 NUTRIENTS
JI Nutrients
PD APR
PY 2020
VL 12
IS 4
AR 1179
DI 10.3390/nu12041179
PG 26
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA LL8VE
UT WOS:000531831300299
PM 32331489
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Lu, W
   Gomez, NM
   Lim, JC
   Guha, S
   O'Brien-Jenkins, A
   Coffey, EE
   Campagno, KE
   McCaughey, SA
   Laties, AM
   Carlsson, LG
   Mitchell, CH
AF Lu, Wennan
   Gomez, Nestor M.
   Lim, Jason C.
   Guha, Sonia
   O'Brien-Jenkins, Ann
   Coffey, Erin E.
   Campagno, Keith E.
   McCaughey, Stuart A.
   Laties, Alan M.
   Carlsson, Leif G.
   Mitchell, Claire H.
TI The P2Y(12) Receptor Antagonist Ticagrelor Reduces Lysosomal pH and
   Autofluorescence in Retinal Pigmented Epithelial Cells From the
   ABCA4(-/-) Mouse Model of Retinal Degeneration
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE P2Y(12) receptor; ticagrelor; age-related macular degeneration;
   lysosomal pH; retinal pigment epithelium; lysosomal storage diseases
ID ACUTE CORONARY SYNDROMES; PLATELET INHIBITION; RPE CELLS; MACULAR
   DEGENERATION; P2X7 RECEPTOR; ACCUMULATION; LIPOFUSCIN; ADENOSINE;
   DEGRADATION; CHANNEL
AB The accumulation of partially degraded lipid waste in lysosomal-related organelles may contribute to pathology in many aging diseases. The presence of these lipofuscin granules is particularly evident in the autofluorescent lysosome-associated organelles of the retinal pigmented epithelial (RPE) cells, and may be related to early stages of age-related macular degeneration. While lysosomal enzymes degrade material optimally at acidic pH levels, lysosomal pH is elevated in RPE cells from the ABCA4(-/-) mouse model of Stargardt's disease, an early onset retinal degeneration. Lowering lysosomal pH through cAMP-dependent pathways decreases accumulation of autofluorescent material in RPE cells in vitro, but identification of an appropriate receptor is crucial for manipulating this pathway in vivo. As the P2Y(12) receptor for ADP is coupled to the inhibitory G(i) protein, we asked whether blocking the P2Y(12) receptor with ticagrelor could restore lysosomal acidity and reduce autofluorescence in compromised RPE cells from ABCA4(-/-) mice. Oral delivery of ticagrelor giving rise to clinically relevant exposure lowered lysosomal pH in these RPE cells. Ticagrelor also partially reduced autofluorescence in the RPE cells of ABCA4(-/-) mice. In vitro studies in ARPE-19 cells using more specific antagonists AR-C69931 and AR-C66096 confirmed the importance of the P2Y(12) receptor for lowering lysosomal pH and reducing autofluorescence. These observations identify P2Y(12) receptor blockade as a potential target to lower lysosomal pH and clear lysosomal waste in RPE cells.
C1 [Lu, Wennan; Gomez, Nestor M.; Lim, Jason C.; Guha, Sonia; O'Brien-Jenkins, Ann; Coffey, Erin E.; Campagno, Keith E.; McCaughey, Stuart A.; Mitchell, Claire H.] Univ Penn, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA.
   [Guha, Sonia; Laties, Alan M.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA.
   [Carlsson, Leif G.] AstraZeneca, Dept Biosci Heart Failure Cardiovasc Renal & Meta, IMED Biotech Unit, Gothenburg, Sweden.
   [Mitchell, Claire H.] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Mitchell, Claire H.] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of California System; University
   of California Los Angeles; AstraZeneca; University of Pennsylvania;
   University of Pennsylvania
RP Mitchell, CH (通讯作者)，Univ Penn, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA.; Mitchell, CH (通讯作者)，Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.; Mitchell, CH (通讯作者)，Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA.
EM chm@upenn.edu
OI Campagno, Keith/0000-0003-1079-947X; Guha, Sonia/0000-0002-7585-8381
FU NIH [EY013434, EY015537, EY001583]; Jody Sack Fund; AstraZeneca;
   NATIONAL EYE INSTITUTE [R01EY013434, R01EY015537, P30EY001583] Funding
   Source: NIH RePORTER
FX This work was supported by grants from the NIH EY013434 and EY015537 and
   core grant EY001583 (CM), the Jody Sack Fund (WL), and AstraZeneca.
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NR 45
TC 13
Z9 13
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 APR 19
PY 2018
VL 9
AR 242
DI 10.3389/fphar.2018.00242
PG 10
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA GD3JW
UT WOS:000430401200001
PM 29725296
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Songstad, AE
   Worthington, KS
   Chirco, KR
   Giacalone, JC
   Whitmore, SS
   Anfinson, KR
   Ochoa, D
   Cranston, CM
   Riker, MJ
   Neiman, M
   Stone, EM
   Mullins, RF
   Tucker, BA
AF Songstad, Allison E.
   Worthington, Kristan S.
   Chirco, Kathleen R.
   Giacalone, Joseph C.
   Whitmore, S. Scott
   Anfinson, Kristin R.
   Ochoa, Dalyz
   Cranston, Cathryn M.
   Riker, Megan J.
   Neiman, Maurine
   Stone, Edwin M.
   Mullins, Robert F.
   Tucker, Budd A.
TI Connective Tissue Growth Factor Promotes Efficient Generation of Human
   Induced Pluripotent Stem Cell-Derived Choroidal Endothelium
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE Age related macular degeneration; Human induced pluripotent stem cells;
   Choroidal endothelial cells; Connective tissue growth factor;
   TNF-related weak inducer of apoptosis receptor
ID MEMBRANE ATTACK COMPLEX; MACULAR-DEGENERATION; MULTIFUNCTIONAL CYTOKINE;
   PROGENITOR CELLS; GENE-EXPRESSION; TWEAK; DIFFERENTIATION;
   TRANSTHYRETIN; EPITHELIUM; PROTEIN
AB Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the Western world. Although, the majority of stem cell research to date has focused on production of retinal pigment epithelial (RPE) and photoreceptor cells for the purpose of evaluating disease pathophysiology and cell replacement, there is strong evidence that the choroidal endothelial cells (CECs) that form the choriocapillaris vessels are the first to be lost in this disease. As such, to accurately evaluate disease pathophysiology and develop an effective treatment, production of patient-specific, stem cell-derived CECs will be required. In this study, we report for the first time a stepwise differentiation protocol suitable for generating human iPSC-derived CEC-like cells. RNA-seq analysis of the monkey CEC line, RF/6A, combined with two statistical screens allowed us to develop media comprised of various protein combinations. In both screens, connective tissue growth factor (CTGF) was identified as the key component required for driving CEC development. A second factor tumor necrosis factor (TNF)-related weak inducer of apoptosis receptor was also found to promote iPSC to CEC differentiation by inducing endogenous CTGF secretion. CTGF-driven iPSC-derived CEC-like cells formed capillary tube-like vascular networks, and expressed the EC-specific markers CD31, ICAM1, PLVAP, vWF, and the CEC-restricted marker CA4. In combination with RPE and photoreceptor cells, patient-specific iPSC derived CEC-like cells will enable scientists to accurately evaluate AMD pathophysiology and develop effective cell replacement therapies.
C1 [Songstad, Allison E.; Worthington, Kristan S.; Chirco, Kathleen R.; Giacalone, Joseph C.; Whitmore, S. Scott; Anfinson, Kristin R.; Ochoa, Dalyz; Cranston, Cathryn M.; Riker, Megan J.; Stone, Edwin M.; Mullins, Robert F.; Tucker, Budd A.] Univ Iowa, Dept Ophthalmol & Visual Sci, Wynn Inst Vis Res, 4136MERF,375 Newton Rd, Iowa City, IA 52242 USA.
   [Neiman, Maurine] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA.
C3 University of Iowa; University of Iowa
RP Tucker, BA (通讯作者)，Univ Iowa, Dept Ophthalmol & Visual Sci, Wynn Inst Vis Res, 4136MERF,375 Newton Rd, Iowa City, IA 52242 USA.
EM budd-tucker@uiowa.edu
RI Worthington, Kristan/AAI-2212-2019; Mullins, Robert F/I-6717-2013
OI Giacalone, Joseph/0000-0003-4404-9749; Worthington,
   Kristan/0000-0002-0693-0685; Stone, Edwin M./0000-0003-3343-4414;
   Whitmore, S. Scott/0000-0003-0161-9625; Tucker,
   Budd/0000-0003-2178-1742; Mullins, Robert/0000-0002-5006-0891
FU Elmer and Sylvia Sramek Charitable Foundation; National Eye Institute
   [NIH RO1 - EY 024605, RO1 - EY026087]; Wynn Institute Endowment for
   Vision Research; NATIONAL EYE INSTITUTE [R01EY026087, R01EY024605,
   P30EY025580] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL
   MEDICAL SCIENCES [T32GM007337] Funding Source: NIH RePORTER
FX We would like to thank the Iowa Lion's Eye Bank and the donors and their
   families for their invaluable contributions. Additionally, we wish to
   thank the Elmer and Sylvia Sramek Charitable Foundation, National Eye
   Institute (NIH RO1 - EY 024605, RO1 - EY026087), and Wynn Institute
   Endowment for Vision Research for their support.
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NR 53
TC 25
Z9 26
U1 1
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD JUN
PY 2017
VL 6
IS 6
BP 1533
EP 1546
DI 10.1002/sctm.16-0399
PG 14
WC Cell & Tissue Engineering
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA EZ2ST
UT WOS:000404561300010
PM 28474838
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Saadane, A
   Mast, N
   Dao, T
   Ahmad, B
   Pikuleva, IA
AF Saadane, Aicha
   Mast, Natalia
   Dao, Tung
   Ahmad, Baseer
   Pikuleva, Irina A.
TI Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and
   Esterification in Photoreceptor Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE acetyl coenzyme A (acetyl-CoA); cholesterol; cholesterol metabolism;
   cytochrome P450; eye; gas chromatography-mass spectrometry (GC-MS);
   pathogenesis; retina; retinal degeneration; retinal metabolism
ID SUBRETINAL DRUSENOID DEPOSITS; LIPOPROTEIN-LIKE PARTICLES; RETICULAR
   MACULAR DISEASE; AGE-RELATED MACULOPATHY; HUMAN BRUCHS MEMBRANE;
   ACYL-COENZYME; GEOGRAPHIC ATROPHY; MOUSE RETINA; LIPID HISTOCHEMISTRY;
   ACYLTRANSFERASE ACAT
AB The process of vision is impossible without the photoreceptor cells, which have a unique structure and specific maintenance of cholesterol. Herein we report on the previously unrecognized cholesterol-related pathway in the retina discovered during follow-up characterizations of Cyp27a1(-/-)Cyp46a1(-/-) mice. These animals have retinal hypercholesterolemia and convert excess retinal cholesterol into cholesterol esters, normally present in the retina in very small amounts. We established that in the Cyp27a1(-/-)Cyp46a1(-/-) retina, cholesterol esters are generated by and accumulate in the photoreceptor outer segments (OS), which is the retinal layer with the lowest cholesterol content. Mouse OS were also found to express the cholesterol-esterifying enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT1), but not lecithin-cholesterol acyltransferase (LCAT), and to differ from humans in retinal expression of ACAT1. Nevertheless, cholesterol esters were discovered to be abundant in human OS. We suggest a mechanism for cholesterol ester accumulation in the OS and that activity impairment of ACAT1 in humans may underlie the development of subretinal drusenoid deposits, a hallmark of age-related macular degeneration, which is a common blinding disease. We generated Cyp27a1(-/-)Cyp46a1(-/-)Acat1(-/-) mice, characterized their retina by different imaging modalities, and confirmed that unesterified cholesterol does accumulate in their OS and that there is photoreceptor apoptosis and OS degeneration in this line. Our results provide insights into the retinal response to local hypercholesterolemia and the retinal significance of cholesterol esterification, which could be cell-specific and both beneficial and detrimental for retinal structure and function.
C1 [Saadane, Aicha; Mast, Natalia; Dao, Tung; Ahmad, Baseer; Pikuleva, Irina A.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, 2085 Adelbert Rd,Rm 303a, Cleveland, OH 44106 USA.
   [Ahmad, Baseer] Univ Hosp Cleveland, Cleveland, OH 44106 USA.
C3 Case Western Reserve University; University Hospitals of Cleveland
RP Pikuleva, IA (通讯作者)，Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, 2085 Adelbert Rd,Rm 303a, Cleveland, OH 44106 USA.
EM iap8@case.edu
OI Saadane, Aicha/0000-0001-9985-2147; Pikuleva, Irina/0000-0001-9742-6232
FU National Institutes of Health [P30 EY11373]; NATIONAL EYE INSTITUTE
   [P30EY011373, R01EY018383] Funding Source: NIH RePORTER
FX We thank the former members of the Pikuleva laboratory, Dr. Saida
   Omarova and Dr. Casey Charvet, for isolating the OS from donors 3-6; Dr.
   Cristine Curcio (University of Alabama at Birmingham) for providing
   retinal sections for these donors; Dr. Krzysztof Palczewski (Case
   Western Reserve University) for providing the anti-rhodopsin antibodies
   B6-30; and the Visual Sciences Research Center Core Facility (supported
   by National Institutes of Health Grant P30 EY11373) for assistance with
   mouse breeding (Heather Butler and Kathryn Franke), animal genotyping
   (John Denker), tissue sectioning (Cathy Doller), and microscopy (Dr.
   Scott Howell). We are also grateful to Dr. Hisashi Fujioka of the Case
   EM core facility and Dr. Patrick Leahy of the Case LCM core facility.
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NR 75
TC 16
Z9 16
U1 0
U2 3
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 SEP 23
PY 2016
VL 291
IS 39
BP 20427
EP 20439
DI 10.1074/jbc.M116.744656
PG 13
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA DX7NN
UT WOS:000384574800012
PM 27514747
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Grudzinski, W
   Krzeminska, I
   Luchowski, R
   Nosalewicz, A
   Gruszecki, WI
AF Grudzinski, Wojciech
   Krzeminska, Izabela
   Luchowski, Rafal
   Nosalewicz, Artur
   Gruszecki, Wieslaw I.
TI Strong-light-induced yellowing of green microalgae Chlorella: A study on
   molecular mechanisms of the acclimation response
SO ALGAL RESEARCH-BIOMASS BIOFUELS AND BIOPRODUCTS
LA English
DT Article
DE Microalgae; Carotenoids; Zeaxanthin; High light stress; Acclimation;
   Photoprotection
ID XANTHOPHYLL CYCLE; NITROGEN STARVATION; CAROTENOID BIOSYNTHESIS;
   OPTIMIZATION; FLUORESCENCE; INTENSITY; GROWTH; LEAVES; PLANTS; DAMAGE
AB Two strains of unicellular microalgae, Chlorella protothecoides and Chlorella vulgaris, subjected to strong light conditions (400 mu mol photons m(-2) s(-1)) turn yellow, as compared to the green control cells cultured at low light intensity (80 mu mol photons m(-2) s(-1)). Such a mechanism is typically interpreted in terms of an adaptive response of algae to overexcitation conditions. In the present work, fluorescence spectroscopy and molecular imaging techniques: fluorescence lifetime imaging microscopy and Raman imaging microscopy, were applied to readdress the problem: whether this process is associated with an acclimation or rather is a manifestation of a photo-degradation process. Yellow coloration of the algal culture exposed to strong light, was found to be associated with accumulation of xanthophyll pigments, predominantly zeaxanthin. The results show that carotenoids, newly synthesized in response to strong light conditions are not energetically coupled to chlorophylls and therefore are not photosynthetically active. On the other hand, over-synthesized xanthophylls can be potentially active as antioxidants, membrane stabilizing agents and, importantly, in shielding cells from intensive radiation, via "molecular sunglasses" mechanism. The latter mechanism has been identified in a cell nucleus and concluded to protect a genetic material against photodamage. Culturing Chlorella at elevated light intensities may also be considered as an alternative source of zeaxanthin, one of the macular pigments protecting human eyes against the age related macular degeneration. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Grudzinski, Wojciech; Gruszecki, Wieslaw I.] Marie Curie Sklodowska Univ, Inst Phys, Dept Biophys, PL-20031 Lublin, Poland.
   [Krzeminska, Izabela; Nosalewicz, Artur] Polish Acad Sci, Bohdan Dobrzanski Inst Agrophys, Doswiadczalna 4, PL-20290 Lublin, Poland.
C3 Maria Curie-Sklodowska University; Polish Academy of Sciences; Bohdan
   Dobrzanski Institute of Agrophysics of the Polish Academy of Sciences
RP Gruszecki, WI (通讯作者)，Marie Curie Sklodowska Univ, Inst Phys, Dept Biophys, PL-20031 Lublin, Poland.
EM wieslaw.gruszecki@umcs.pl
RI Nosalewicz, Artur/O-6296-2019
OI Nosalewicz, Artur/0000-0001-5864-5619; Gruszecki,
   Wieslaw/0000-0002-8245-3913; Krzeminska, Izabela/0000-0002-0125-717X;
   Luchowski, Rafal/0000-0003-1156-8059; Grudzinski,
   Wojciech/0000-0002-8825-1423
FU Foundation for Polish Science within the TEAM program [TEAM/2011-7/2];
   European Regional Development Fund
FX This research has been performed within the framework of the project,
   "Molecular Spectroscopy for BioMedical Studies" financed by the
   Foundation for Polish Science within the TEAM program (TEAM/2011-7/2).
   The research was carried out with the equipment purchased thanks to the
   financial support of the European Regional Development Fund in the
   framework of the Development of Eastern Poland Operational Programme.
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NR 43
TC 21
Z9 21
U1 0
U2 53
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 2211-9264
J9 ALGAL RES
JI Algal Res.
PD JUN
PY 2016
VL 16
BP 245
EP 254
DI 10.1016/j.algal.2016.03.021
PG 10
WC Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology
GA DL4MD
UT WOS:000375610000029
DA 2022-11-30
ER

PT J
AU Zeng, SM
   Whitmore, SS
   Sohn, EH
   Riker, MJ
   Wiley, LA
   Scheetz, TE
   Stone, EM
   Tucker, BA
   Mullins, RF
AF Zeng, Shemin
   Whitmore, S. Scott
   Sohn, Elliott H.
   Riker, Megan J.
   Wiley, Luke A.
   Scheetz, Todd E.
   Stone, Edwin M.
   Tucker, Budd A.
   Mullins, Robert F.
TI Molecular response of chorioretinal endothelial cells to complement
   injury: implications for macular degeneration
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE age-related macular degeneration; complement system; endothelial cells;
   matrix metalloproteinase
ID MEMBRANE ATTACK COMPLEX; FACTOR-H POLYMORPHISM; CHOROIDAL THICKNESS;
   AGE; DRUSEN; CHORIOCAPILLARIS; ACTIVATION; REGULATORS; MODEL; RISK
AB Age-related macular degeneration (AMD) is a common, blinding disease of the elderly in which macular photoreceptor cells, retinal pigment epithelium and choriocapillaris endothelial cells ultimately degenerate. Recent studies have found that degeneration of the choriocapillaris occurs early in this disease and that endothelial cell drop-out is concomitant with increased deposition of the complement membrane attack complex (MAC) at the choroidal endothelium. However, the impact of MAC injury to choroidal endothelial cells is poorly understood. To model this event in vitro, and to study the downstream consequences of MAC injury, endothelial cells were exposed to complement from human serum, compared to heat-inactivated serum, which lacks complement components. Cells exposed to complement components in human serum showed increased labelling with antibodies directed against the MAC, time- and dose-dependent cell death, as assessed by lactate dehydrogenase assay and increased permeability. RNA-Seq analysis following complement injury revealed increased expression of genes associated with angiogenesis including matrix metalloproteinase (MMP)-3 and -9, and VEGF-A. The MAC-induced increase in MMP9RNA expression was validated using C5-depleted serum compared to C5-reconstituted serum. Increased levels of MMP9 were also established, using western blot and zymography. These data suggest that, in addition to cell lysis, complement attack on choroidal endothelial cells promotes an angiogenic phenotype in surviving cells. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 Univ Iowa, Stephen A Wynn Inst Vis Res, Iowa City, IA USA.
   Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
C3 University of Iowa; University of Iowa
RP Mullins, RF (通讯作者)，Stephen A Wynn Inst Vis Res, 375 Newton Rd, Iowa City, IA 52242 USA.
EM Robert-Mullins@uiowa.edu
RI Mullins, Robert F/I-6717-2013
OI Scheetz, Todd/0000-0002-1965-5811; Sohn, Elliott/0000-0002-3778-9362;
   Wiley, Luke/0000-0003-0136-2364; Whitmore, S. Scott/0000-0003-0161-9625;
   Tucker, Budd/0000-0003-2178-1742; Mullins, Robert/0000-0002-5006-0891;
   Stone, Edwin M./0000-0003-3343-4414
FU National Institutes for Health (NIH) [EY-024605, EY-023187,
   1-DP2-OD007483-01]; Elmer and Sylvia Sramek Charitable Foundation;
   Ronald and Annette Massman Choroideremia Research Fund; Howard F Ruby
   Endowment for Human Retinal Engineering; Stephen A Wynn Foundation;
   Hansjoerg EJW Kolder Professorship in Best Disease Research; Martin and
   Ruth Carver Chair in Ocular Cell Biology; NATIONAL EYE INSTITUTE
   [R01EY023187, R01EY024605] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008629] Funding Source: NIH
   RePORTER; OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH
   [DP2OD007483] Funding Source: NIH RePORTER
FX Supported in part by the National Institutes for Health (NIH; Grant Nos
   EY-024605, EY-023187 and 1-DP2-OD007483-01), the Elmer and Sylvia Sramek
   Charitable Foundation, the Ronald and Annette Massman Choroideremia
   Research Fund, the Howard F Ruby Endowment for Human Retinal
   Engineering, the Stephen A Wynn Foundation, the Hansjoerg EJW Kolder
   Professorship in Best Disease Research and the Martin and Ruth Carver
   Chair in Ocular Cell Biology.
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PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3417
EI 1096-9896
J9 J PATHOL
JI J. Pathol.
PD FEB
PY 2016
VL 238
IS 3
BP 446
EP 456
DI 10.1002/path.4669
PG 11
WC Oncology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Pathology
GA DC1QA
UT WOS:000368990000010
PM 26564985
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Wang, HB
   Fotheringham, L
   Wittchen, ES
   Hartnett, ME
AF Wang, Haibo
   Fotheringham, Lori
   Wittchen, Erika S.
   Hartnett, M. Elizabeth
TI Rap1 GTPase Inhibits Tumor Necrosis Factor-alpha-Induced Choroidal
   Endothelial Migration via NADPH Oxidase- and NF-kappa B-Dependent
   Activation of Rac1
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; CELL TRANSMIGRATION; ROS GENERATION; TNF-ALPHA;
   DRUSEN; VEGF; NEOVASCULARIZATION; DEPOSITS; DISEASES; BINDING
AB Macrophage-derived tumor necrosis factor (TNF)-alpha has been found in choroidal neovascularization (CNV) surgically removed from patients with age-related macular degeneration. However, the rote of TNF-alpha in CNV development remains unclear. In a murine laser-induced CNV model, compared with un-lasered controls, TNF-alpha mRNA was increased in retinal pigment epithelial and choroidal tissue, and TNF-alpha colocalized with lectin-stained migrating choroidal endothelial cells (CECs). Inhibition of TNF-alpha with a neutralizing antibody reduced CNV volume and reactive oxygen species (ROS) Level around CNV. In CECs, pretreatment with the antioxidant apocynin or knockdown of p22phox, a subunit of NADPH oxidase, inhibited TNF-alpha-induced ROS generation. Apocynin reduced TNF-alpha-induced NF-kappa B and Rac1 activation, and inhibited TNF-alpha-induced CEC migration. TNF-alpha-induced Rac1 activation and CEC migration were inhibited by NF-kappa B inhibitor Bay11-7082. Overexpression of Rap1a prevented TNF-alpha-induced ROS generation and reduced NF-kappa B and Rac1 activation. Activation of Rap1 by 8-(4-chlorophenylthio) adenosine-2'-O-Me-cAMP prevented TNF-alpha-induced CEC migration and reduced laser-induced CNV volume, ROS generation, and activation of NF-kappa B and Rac1. These findings provide evidence that active Rap1a inhibits TNF-alpha-induced CEC migration by inhibiting NADPH oxidase-dependent NF-kappa B and Rac1 activation and suggests that Rap1a de-escalates CNV development by interfering with ROSdependent signaling in several steps of the pathogenic process.
C1 [Wang, Haibo; Fotheringham, Lori; Hartnett, M. Elizabeth] Univ Utah, John A Moran Eye Ctr, Salt Lake City, UT 84132 USA.
   [Wittchen, Erika S.] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC USA.
C3 Utah System of Higher Education; University of Utah; University of North
   Carolina; University of North Carolina Chapel Hill
RP Hartnett, ME (通讯作者)，Univ Utah, 65 N Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM me.hartnett@hsc.utah.edu
FU NIH [EY014800, R01 R01EY015130, R01EY017011]; March of Dimes
   [6-FY13-75]; Research to Prevent Blindness, Inc., New York, NY, grant;
   NATIONAL EYE INSTITUTE [R01EY015130, P30EY014800, R01EY017011] Funding
   Source: NIH RePORTER
FX Supported by NIH grants EY014800, R01 R01EY015130, and R01EY017011
   (M.E.H.), March of Dimes grant 6-FY13-75 (M.E.H.), and Research to
   Prevent Blindness, Inc., New York, NY, grant to the Department of
   Ophthalmology and Visual Sciences, University of Utah.
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NR 34
TC 29
Z9 31
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD DEC
PY 2015
VL 185
IS 12
BP 3316
EP 3325
DI 10.1016/j.ajpath.2015.08.017
PG 10
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA CX8CB
UT WOS:000365929000016
PM 26476350
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Kimura, K
   Orita, T
   Liu, Y
   Yang, Y
   Tokuda, K
   Kurakazu, T
   Noda, T
   Yanai, R
   Morishige, N
   Takeda, A
   Ishibashi, T
   Sonoda, KH
AF Kimura, Kazuhiro
   Orita, Tomoko
   Liu, Yang
   Yang, Yang
   Tokuda, Kazuhiro
   Kurakazu, Taishi
   Noda, Takeshi
   Yanai, Ryoji
   Morishige, Naoyuki
   Takeda, Atsunobu
   Ishibashi, Tatsuro
   Sonoda, Koh-Hei
TI Attenuation of EMT in RPE cells and subretinal fibrosis by an RAR-gamma
   agonist
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE Retinal pigment epithelial cell; Transforming growth factor-beta
   (TGF-beta); Epithelial-mesenchymal transition; Extracellular matrix;
   Subretinal fibrosis; Age-related macular degeneration
ID GROWTH-FACTOR-BETA; PIGMENT EPITHELIAL-CELLS; HUMAN TENON FIBROBLASTS;
   TRANS-RETINOIC ACID; MACULAR DEGENERATION; PROLIFERATIVE
   VITREORETINOPATHY; MESENCHYMAL TRANSITION; CONTRACTION; INHIBITION;
   INDUCTION
AB Subretinal fibrosis contributes to the loss of vision associated with age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells play a key role in the pathogenesis of AMD including the fibrotic reaction. We examined the role of retinoic acid receptor-gamma (RAR-gamma) in the epithelial-mesenchymal transition (EMT) and other fibrosis-related processes in mouse RPE cells cultured in a type I collagen gel. Transforming growth factor-beta 2 (TGF-beta 2)-induced collagen gel contraction mediated by the RPE cells was inhibited by the RAR-gamma agonist R667 in a concentration- and time-dependent manner. Expression of the mesenchymal markers alpha-smooth muscle actin and fibronectin, the release of interleukin-6, and the phosphorylation of paxillin, mitogen-activated protein kinases (ERK, p38, and JNK), Smad2, and AKT induced by TGF-beta 2 were also suppressed by the RAR-gamma agonist. Furthermore, gelatin zymography and immunoblot analysis revealed that the TGF-beta 2-induced release of matrix metalloproteinase (MMP)-2, MMP-3, MMP-8, and MMP-9 from RPE cells was inhibited by R667, and the MMP inhibitor GM6001 attenuated TGF-beta 2-induced RPE cell contraction. Finally, immunohistofluorescence analysis with antibodies to glial fibrillary acidic protein showed that R667 inhibited the development of subretinal fibrosis in a mouse model in vivo. Our results thus suggest that RAR-gamma agonists may prove effective for the treatment of subretinal fibrosis associated with AMD.
C1 [Kimura, Kazuhiro; Orita, Tomoko; Liu, Yang; Tokuda, Kazuhiro; Kurakazu, Taishi; Noda, Takeshi; Yanai, Ryoji; Morishige, Naoyuki; Sonoda, Koh-Hei] Yamaguchi Univ, Grad Sch Med, Dept Ophthalmol, Ube, Yamaguchi 7558505, Japan.
   [Yang, Yang; Takeda, Atsunobu; Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan.
C3 Yamaguchi University; Kyushu University
RP Kimura, K (通讯作者)，Yamaguchi Univ, Grad Sch Med, Dept Ophthalmol, 1-1-1 Minami Kogushi, Ube, Yamaguchi 7558505, Japan.
EM k.kimura@yamaguchi-u.ac.jp
FU Takeda Science Foundation; Grants-in-Aid for Scientific Research
   [26462663, 26861453] Funding Source: KAKEN
FX This study was supported by Takeda Science Foundation. We thank Yukari
   Mizuno and Shizuka Murata for technical assistance.
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NR 39
TC 40
Z9 42
U1 0
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
EI 1432-1440
J9 J MOL MED
JI J. Mol. Med.
PD JUL
PY 2015
VL 93
IS 7
BP 749
EP 758
DI 10.1007/s00109-015-1289-8
PG 10
WC Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Research & Experimental Medicine
GA CK9AC
UT WOS:000356530700006
PM 25947075
DA 2022-11-30
ER

PT J
AU Thibaut, M
   Tran, THC
   Szaffarczyk, S
   Boucart, M
AF Thibaut, Miguel
   Thi Ha Chau Tran
   Szaffarczyk, Sebastien
   Boucart, Muriel
TI The contribution of central and peripheral vision in scene
   categorization: A study on people with central vision loss
SO VISION RESEARCH
LA English
DT Article
DE Scene perception; Peripheral vision; Age-related macular degeneration;
   Low vision
ID LARGE VISUAL ECCENTRICITIES; PREFERRED RETINAL LOCUS; AGE-RELATED
   MACULOPATHY; MACULAR DEGENERATION; OBJECT RECOGNITION; NATURAL SCENES;
   REORGANIZATION; DISEASE; COLOR; GIST
AB Studies in normally sighted people suggest that scene recognition is based on global physical properties and can be accomplished by the low resolution of peripheral vision. We examine the contribution of peripheral and central vision in scene gist recognition in patients with central vision loss and age-matched controls. Twenty-one patients with neovascular age related macular degeneration (AMD), with a visual acuity lower than 20/50, and 15 age-matched normally sighted controls participated in a natural/ urban scene categorization task. The stimuli were colored photographs of natural scenes presented randomly at one of five spatial locations of a computer screen: centre, top left, top right, bottom left and bottom right at 12 degrees eccentricity. Sensitivity (d') and response times were recorded. Normally sighted people exhibited higher sensitivity and shorter response times when the scene was presented centrally than for peripheral pictures. Sensitivity was lower and response times were longer for people with AMD than for controls at all spatial location. In contrast to controls patients were not better for central than for peripheral pictures. The results of normally sighted controls indicate that scene categorization can be accomplished by the low resolution of peripheral vision but central vision remains more efficient than peripheral vision for scene gist recognition. People with central vision loss likely categorized scenes on the basis of low frequency information both in normal peripheral vision and in low acuity central vision. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Thibaut, Miguel; Thi Ha Chau Tran; Szaffarczyk, Sebastien; Boucart, Muriel] Univ Lille Nord France, CNRS, Lab Neurosci & Pathol Fonct, Lille, France.
   [Thi Ha Chau Tran] Hop St Vincent de Paul, Serv Ophtalmol, Lille, France.
C3 Centre National de la Recherche Scientifique (CNRS); Universite de Lille
   - ISITE; Universite de Lille
RP Boucart, M (通讯作者)，CHRU Lille, Hop Roger Salengro, Lab Neurosci & Pathol Fonct, F-59037 Lille, France.
EM m-boucart@chru-lille.fr
RI TRAN, Thi Ha Chau/AAF-2162-2020
OI TRAN, Thi Ha Chau/0000-0001-9066-7092
FU French national research agency (ANR Low vision)
FX The authors are grateful to Aude Oliva for providing the photographs of
   scenes, to Sandrine Delord for computing the amplitude spectra of
   natural and urban scenes and to Steven Ola for checking the English of
   the manuscript. The study was funded by a grant from the French national
   research agency (ANR Low vision) to the last author.
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NR 43
TC 16
Z9 17
U1 2
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
EI 1878-5646
J9 VISION RES
JI Vision Res.
PD MAY
PY 2014
VL 98
BP 46
EP 53
DI 10.1016/j.visres.2014.03.004
PG 8
WC Neurosciences; Ophthalmology; Psychology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology; Psychology
GA AG7UJ
UT WOS:000335624000005
PM 24657253
OA Bronze
DA 2022-11-30
ER

PT J
AU Dundar, S
   Ozcura, F
   Meteoglu, I
   Kara, ME
AF Dundar, Sema
   Ozcura, Fatih
   Meteoglu, Ibrahim
   Kara, Mehmet Erkut
TI Effects of long-term passive smoking on the vascular endothelial growth
   factor and apoptosis marker expression in the retina and choroid: an
   experimental study
SO TURKISH JOURNAL OF MEDICAL SCIENCES
LA English
DT Article
DE Smoking; age related macular degeneration; vascular endothelial growth
   factor; apoptosis; retina; choroid
ID MACULAR DEGENERATION; CIGARETTE-SMOKING; FACTOR VEGF; ASSOCIATION; RISK
AB Aim: To investigate the effects of smoking, reported as a risk factor for age related macular degeneration (ARMD), on the vascular endothelial growth factor (VEGF) expression and apoptosis in the retina and choroid of rats.
   Materials and methods: This experimental study included 38 Sprague-Dawley rats. The rats were randomly assigned into 4 groups. Groups 1 (males) and 2 (females) were exposed to smoke beginning on day 21 after birth, whereas groups 3 (males) and 4 (females) were not exposed to smoke. At the end of the fourth month, the right eyes of all of the rats were enucleated. Immunohistochemical analysis was performed in the enucleated eyes in terms of the VEGF and apoptosis markers, namely caspase-3, Bcl-X, and p53. Comparisons between the groups were performed using the Mann-Whitney U test.
   Results: The VEGF expression in the retina and choroid increased significantly in rats exposed to smoking. This significant difference did not change between the sexes. There were no significant differences in terms of Bcl-X and p53 expressions between the groups; however, the caspase-3 expression increased significantly in the photoreceptor layer in rats exposed to smoking.
   Conclusion: Our findings show that smoking significantly increases the VEGF expression in many of the retinal layers and choroid. Smoking also increases caspase-3 expression only in the photoreceptor layer. According to these findings, smoking may be a risk factor for retinal vascular disease such as exudative ARMD, via stimulating the VEGF.
C1 [Ozcura, Fatih] Dumlupinar Univ, Dept Ophthalmol, Fac Med, TR-43270 Kutahya, Turkey.
   [Dundar, Sema] Adnan Menderes Univ, Dept Ophthalmol, Fac Med, Aydin, Turkey.
   [Meteoglu, Ibrahim] Adnan Menderes Univ, Dept Pathol, Fac Med, Aydin, Turkey.
   [Kara, Mehmet Erkut] Adnan Menderes Univ, Dept Anat, Fac Med, Aydin, Turkey.
C3 Dumlupinar University; Adnan Menderes University; Adnan Menderes
   University; Adnan Menderes University
RP Ozcura, F (通讯作者)，Dumlupinar Univ, Dept Ophthalmol, Fac Med, Cent Campus, TR-43270 Kutahya, Turkey.
EM fatihozcura@yahoo.com
RI kara, mehmet/AAR-1993-2020; Ozcura, Fatih/F-8640-2011
OI kara, mehmet/0000-0002-5056-1688; Ozcura, Fatih/0000-0001-6482-180X
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NR 27
TC 5
Z9 5
U1 0
U2 7
PU TUBITAK SCIENTIFIC & TECHNICAL RESEARCH COUNCIL TURKEY
PI ANKARA
PA ATATURK BULVARI NO 221, KAVAKLIDERE, ANKARA, 00000, TURKEY
SN 1300-0144
EI 1303-6165
J9 TURK J MED SCI
JI Turk. J. Med. Sci.
PD JUN
PY 2012
VL 42
IS 3
BP 377
EP 383
DI 10.3906/sag-0912-457
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 949IG
UT WOS:000304569300002
OA Green Submitted, Bronze
DA 2022-11-30
ER

PT J
AU Jensen, LD
   Rouhi, P
   Cao, ZQ
   Lanne, T
   Wahlberg, E
   Cao, YH
AF Jensen, Lasse Dahl
   Rouhi, Pegah
   Cao, Ziquan
   Lanne, Toste
   Wahlberg, Eric
   Cao, Yihai
TI Zebrafish Models to Study Hypoxia-Induced Pathological Angiogenesis in
   Malignant and Nonmalignant Diseases
SO BIRTH DEFECTS RESEARCH PART C-EMBRYO TODAY-REVIEWS
LA English
DT Review
DE zebrafish; angiogenesis; cancer; metastasis; retinopathy; hypoxia
ID TUMOR-CELL DISSEMINATION; CARDIOVASCULAR-SYSTEM; HEART REGENERATION;
   RETINAL ANGIOGENESIS; VASCULAR DEVELOPMENT; ENDOTHELIAL-CELLS; GENE;
   MUTATIONS; VESSEL; GRIDLOCK
AB Most in vivo preclinical disease models are based on mouse and other mammalian systems. However, these rodent-based model systems have considerable limitations to recapitulate clinical situations in human patients. Zebrafish have been widely used to study embryonic development, behavior, tissue regeneration, and genetic defects. Additionally, zebrafish also provides an opportunity to screen chemical compounds that target a specific cell population for drug development. Owing to the availability of various genetically manipulated strains of zebrafish, immune privilege during early embryonic development, transparency of the embryos, and easy and precise setup of hypoxia equipment, we have developed several disease models in both embryonic and adult zebrafish, focusing on studying the role of angiogenesis in pathological settings. These zebrafish disease models are complementary to the existing mouse models, allowing us to study clinically relevant processes in cancer and nonmalignant diseases, which otherwise would be difficult to study in mice. For example, dissemination and invasion of single human or mouse tumor cells from the primary site in association with tumor angiogenesis can be studied under normoxia or hypoxia in zebrafish embryos. Hypoxia-induced retinopathy in the adult zebrafish recapitulates the clinical situation of retinopathy development in diabetic patients or age-related macular degeneration. These zebrafish disease models offer exciting opportunities to understand the mechanisms of disease development, progression, and development of more effective drugs for therapeutic intervention. Birth Defects Research (Part C) 93: 182-193, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Jensen, Lasse Dahl; Rouhi, Pegah; Cao, Ziquan; Cao, Yihai] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden.
   [Jensen, Lasse Dahl; Cao, Ziquan; Lanne, Toste; Wahlberg, Eric; Cao, Yihai] Linkoping Univ, Inst Med & Hlth, Linkoping, Sweden.
C3 Karolinska Institutet; Linkoping University
RP Jensen, LD (通讯作者)，Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden.
EM lasse.jensen@ki.se; yihai.cao@ki.se
OI Jensen, Lasse/0000-0003-2338-357X; Lanne, Toste/0000-0002-9095-403X
FU Swedish Research Council; Swedish Cancer Foundation; Karolinska
   Institute Foundation; Torsten and Ragnar Soderberg's Foundation
FX This work is supported by the laboratory of Y.C. through research grants
   from the Swedish Research Council, the Swedish Cancer Foundation, the
   Karolinska Institute Foundation, and the Torsten and Ragnar Soderberg's
   Foundation. Y.C is a Chang Jiang Scholar at the Shandong University,
   China.
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NR 84
TC 20
Z9 20
U1 3
U2 33
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-975X
EI 1542-9768
J9 BIRTH DEFECTS RES C
JI Birth Defects Res. Part C-Embryo Today-Rev.
PD JUN
PY 2011
VL 93
IS 2
BP 182
EP 193
DI 10.1002/bdrc.20203
PG 12
WC Developmental Biology; Reproductive Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Developmental Biology; Reproductive Biology
GA 776OJ
UT WOS:000291545600007
PM 21671357
DA 2022-11-30
ER

PT J
AU Hepburn, NJ
   Ruseva, MM
   Harris, CL
   Morgan, BP
AF Hepburn, N. J.
   Ruseva, M. M.
   Harris, C. L.
   Morgan, B. P.
TI Complement, roles in renal disease and modulation for therapy
SO CLINICAL NEPHROLOGY
LA English
DT Review
DE complement; therapy; inflammatory diseases; recombinant therapeutics
ID HEMOLYTIC-UREMIC SYNDROME; ISCHEMIA-REPERFUSION INJURY;
   SYSTEMIC-LUPUS-ERYTHEMATOSUS; ANTIGEN-INDUCED ARTHRITIS; FACTOR-H
   POLYMORPHISM; BYPASS GRAFT-SURGERY; REMOTE ORGAN INJURY; FACTOR C5
   PROTECTS; I-RELATED RECEPTOR; ALTERNATIVE PATHWAY
AB The complement system, an essential part of the innate immune system, defends the host against invading pathogens, prevents immune complex disease and aids the acquired immune response. Under normal conditions the host is protected from complement attack by an array of complement regulatory proteins. However, in certain contexts inappropriate complement activation can occur associating the C system with a variety of disease pathologies. This review focuses upon the role complement plays in a number of renal pathologies as well as the role of complement in three examples of extrarenal diseases: paroxysmal nocturnal hemoglobinuria, age-related macular degeneration and liver fibrosis. From the evidence discussed it is clear that mutations or polymorphisms in the complement regulators resulting in reduced levels or inefficient action dramatically enhance susceptibility to certain diseases and in particular render the kidney more vulnerable to complement attack. Additionally, deficiency in the complement components can predispose to disease through reduced clearance of apoptotic cells and subsequent generation of complement activating autoantibodies or enhanced formation of convertases resulting in heightened complement activation. As complement has devastating effects, in such disease contexts it has become a therapeutic target. Therapeutic intervention strategies discussed here focus upon the use of recombinant agents, the most promising of which are the anti-C5 antibody-derived reagents. These agents have proved effective in the treatment of paroxysmal nocturnal hemoglobinuria, nephritis and ischemia-reperfusion injuries and will no doubt, along with other reagents currently being developed, prove invaluable in the treatment of renal pathologies.
C1 [Hepburn, N. J.; Ruseva, M. M.; Harris, C. L.; Morgan, B. P.] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff CF14 4XN, S Glam, Wales.
C3 Cardiff University
RP Hepburn, NJ (通讯作者)，Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Henry Wellcome Bldg,Heath Pk, Cardiff CF14 4XN, S Glam, Wales.
EM hepburnnj@cardiff.ac.uk
OI Morgan, Paul/0000-0003-4075-7676
FU Medical Research Council [G0701298] Funding Source: Medline
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NR 176
TC 7
Z9 7
U1 0
U2 3
PU DUSTRI-VERLAG DR KARL FEISTLE
PI DEISENHOFEN-MUENCHEN
PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY
SN 0301-0430
J9 CLIN NEPHROL
JI Clin. Nephrol.
PD NOV
PY 2008
VL 70
IS 5
BP 357
EP 376
PG 20
WC Urology & Nephrology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Urology & Nephrology
GA 375IA
UT WOS:000261106200001
PM 19000536
DA 2022-11-30
ER

PT J
AU Inbaraj, BS
   Lu, H
   Hung, CF
   Wu, WB
   Lin, CL
   Chen, BH
AF Inbaraj, B. Stephen
   Lu, H.
   Hung, C. F.
   Wu, W. B.
   Lin, C. L.
   Chen, B. H.
TI Determination of carotenoids and their esters in fruits of Lycium
   barbarum Linnaeus by HPLC-DAD-APCI-MS
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Lycium barbarum Linnaeus; carotenoid esters; HPLC-DAD-APCI-MS; GC
ID QUANTIFICATION; IDENTIFICATION; FLAVONOIDS; ZEAXANTHIN; EXTRACTS;
   ISOMERS
AB The fruit of Lycium barbarum Linnaeus, a traditional Chinese herb containing functional components such as carotenoids, flavonoids and polysaccharides, has been widely used in the health food industry because of its possible role in the prevention of chronic disease like age-related macular degeneration. The objectives of this study were to develop a high performance liquid chromatography-photo diode array detection-mass spectrometry (HPLC-DAD-MS) method with atmospheric pressure chemical ionization (APCl) mode for qualitative and quantitative analyses of carotenoids in fruits of L. barbarum. Dried samples of L. barbarum were subjected to extraction without saponification or extraction followed by saponification. A C30 column with a gradient mobile phase of methylene chloride (100%) and methanol-acetonitrile-water (81:14:5, v/v/v) was used to separate carotenoids, with a total of 11 free carotenoids and 7 carotenoid esters being resolved from unsaponified and saponified L. barbarum extracts within 51 and 41 min, respectively. The fatty acid composition of carotenoid esters was confirmed by gas chromatography. Zeaxanthin dipalmitate (1143.7 mu g/g) was present in the largest amount, followed by beta-cryptoxanthin monopalmitate and its two isomers (32.9-68.5 mu g/g), zeaxanthin monopalmitate and its two isomers (11.3-62.8 mu g/g), all-trans-beta-carotene (23.7 mu g/g) and all-trans-zeaxanthin (1.4 mu g/g). (C) 2008 Elsevier B.V. All rights reserved.
C1 [Inbaraj, B. Stephen; Lu, H.; Chen, B. H.] Fu Jen Catholic Univ, Dept Food Sci, Taipei 242, Taiwan.
   [Hung, C. F.; Wu, W. B.] Fu Jen Catholic Univ, Sch Med, Taipei 242, Taiwan.
   [Lin, C. L.] Cathay Gen Hosp, Dept Endocrinol & Metab, Taipei, Taiwan.
   [Chen, B. H.] Fu Jen Catholic Univ, Grad Inst Med, Taipei 242, Taiwan.
C3 Fu Jen Catholic University; Fu Jen Catholic University; Cathay General
   Hospital; Fu Jen Catholic University
RP Chen, BH (通讯作者)，Fu Jen Catholic Univ, Dept Food Sci, Taipei 242, Taiwan.
EM 002622@mail.fju.edu.tw
RI Inbaraj, Baskaran Stephen/AAW-2077-2021; Hung, Chi-Feng/AAL-4977-2021;
   Stephen Inbaraj, Baskaran/AEM-6809-2022; Inbaraj, Baskaran
   Stephen/Q-9419-2019
OI Inbaraj, Baskaran Stephen/0000-0003-4301-7614; Hung,
   Chi-Feng/0000-0003-3478-5451; Stephen Inbaraj,
   Baskaran/0000-0003-4301-7614; 
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NR 21
TC 180
Z9 206
U1 7
U2 124
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 AUG 5
PY 2008
VL 47
IS 4-5
BP 812
EP 818
DI 10.1016/j.jpba.2008.04.001
PG 7
WC Chemistry, Analytical; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Pharmacology & Pharmacy
GA 320FY
UT WOS:000257220300024
PM 18486400
DA 2022-11-30
ER

PT J
AU Cedrone, C
   Ricci, F
   Nucci, C
   Cesareo, M
   Macri, G
   Culass, F
AF Cedrone, Claudio
   Ricci, Federico
   Nucci, Carlo
   Cesareo, Massimo
   Macri, Giuseppe
   Culass, Franco
TI Age-specific changes in the Prevalence of best-Corrected Visual
   impairment in an Italian population
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE best-corrected visual impairment; prevalence; age-specific; changes
ID BLINDNESS; EYE; ADULTS; DISABILITY; CATARACT; VISION; ACUITY; HEALTH
AB Purpose: To investigate changes in the prevalence of visual impairment in an Italian population from 1988 to 2000. Methods: Standardized ophthalmologic examinations were administered to citizens of Ponza, Italy aged 40-87 years in 1988 and 2000. Visual Acuity (VA) was measured using a standard logarithmic chart. Visual fields (VF) were tested in all subjects with diagnosed or suspected glaucoma or hereditary degenerative retinopathy. Visual impairment was classified as blindness (VA > 1.3 LogMAR or VF < 10 degrees around central fixation) or low vision (VA > 0.5 to 1.3 LogMAR or VF < 20 degrees to 10 degrees) according to WHO criteria. Results: The prevalence of binocular total visual impairments decreased significantly among 64-75 year-olds (from 6.7% to 2.6%, p = 0.045), and almost significantly among 40-51 year-olds (from 2.4%, 95% Cl 1.1-5.3, to 0.0%, 95% Cl 0.0-1.3). By 2000, visual impairment was no longer significantly associated with female gender, and age 64-75 years; the mean age of subjects with vision-impairing cataract, diabetic retinopathy, or age-related macular degeneration had risen significantly. Conclusions: A decline in the prevalence of visual impairment, particularly in cataract-associated visual impairment was found in the middle-aged groups. The progression of age-related eye diseases seems to have slowed in this population possibly due to improvements in the life expectancy and socio-economic conditions.
C1 Univ Roma Tor Vergata, Dipartimento Biopatol & Diagnost Immagini, Cattedra Ott Fisiopatol, I-00133 Rome, Italy.
   Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy.
C3 University of Rome Tor Vergata; Sapienza University Rome
RP Cedrone, C (通讯作者)，Univ Roma Tor Vergata, Dipartimento Biopatol & Diagnost Immagini, Cattedra Ott Fisiopatol, Via Montpellier 1, I-00133 Rome, Italy.
EM cedrone@uniroma2.it
RI ricci, federico/AAC-3836-2020
OI ricci, federico/0000-0002-4224-9280
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NR 22
TC 5
Z9 5
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0928-6586
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD SEP-OCT
PY 2007
VL 14
IS 5
BP 320
EP 326
DI 10.1080/09286580701316116
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 228OM
UT WOS:000250739300008
PM 17994442
DA 2022-11-30
ER

PT J
AU Gunasekera, RS
   Sewgobind, K
   Desai, S
   Dunn, L
   Black, HS
   McKeehan, WL
   Patil, B
AF Gunasekera, Richard S.
   Sewgobind, Kiran
   Desai, Smruti
   Dunn, Larry
   Black, Homer S.
   McKeehan, Wallace L.
   Patil, Bhimanagouda
TI Lycopene and lutein inhibit proliferation in rat prostate carcinoma
   cells
SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
LA English
DT Article
ID CYCLE PROGRESSION; CITRUS PECTIN; VITAMIN-C; CANCER; CAROTENOIDS;
   GROWTH; RECEPTOR; IRRADIATION; STORAGE; IGF
AB Consumption of lycopene, a carotenoid without provitamin A activity, has been associated with a lower risk of prostate and breast cancer. Lutein is another carotenoid that may be associated with a reduced risk of age-related macular degeneration, the leading cause of blindness in adults 65 years of age and older. Bioactive compounds such as lycopene and lutein, derived from natural plant sources, have been shown to act at low substrate levels through the action of intrinsic cytokines and growth factors and their receptors within tissues, particularly those of the fibroblast growth factor and transforming growth factor beta families. The effects of grapefruit-derived and commercial lycopene and lutein preparations on androgen independent cultured malignant type H tumor cells [Dunning R3327AT3 or AT3 cells (androgen-responsive, slow-growing tumor cells will? well developed epithelium and stroma)] were compared to their benign parent type I tumor epithelial cells (DTE). Results demonstrated that both lycopene, in an a-cyclodextrin water soluble carrier, and lutein inhibited malignant AT3 cells in a concentration and time-dependent manner. No such effect was observed when benign DTE cells were examined, demonstrating selective inhibition of extremely malignant AT3 prostate cancer cells relative to their benign parent. Lutein demonstrated a similar but slightly diminished response as lycopene. When cells were treated with cocktails of lycopene and lutein, no synergistic or additive effect occurred. These studies are consistent with epidemiological studies that show inverse relationships of these carotenoids with prostate cancer.
C1 Univ Houston, Victoria, TX 77901 USA.
   Texas A&M Univ, Ctr Hlth Sci, Ctr Canc Biol & Nutr, Houston, TX 77030 USA.
   Victoria Coll, Victoria, TX 77901 USA.
   Baylor Coll Med, Houston, TX 77030 USA.
   Texas A&M Univ, Dept Hort Sci, Vegetable & Fruit Improvement Ctr, College Stn, TX 77845 USA.
C3 University of Houston System; University of Houston; University of
   Houston Victoria; Texas A&M University System; Baylor College of
   Medicine; Texas A&M University System; Texas A&M University College
   Station
RP Gunasekera, RS (通讯作者)，Univ Houston, Victoria, TX 77901 USA.
EM GunasekeraR@uhv.edu
RI Patil, Bhimu S/C-7620-2013
OI Patil, Bhimu S/0000-0001-7189-0432
CR *AM CANC SOC, 2004, LEAD SIT NEW CANC CA
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NR 30
TC 57
Z9 64
U1 0
U2 16
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0163-5581
EI 1532-7914
J9 NUTR CANCER
JI Nutr. Cancer
PY 2007
VL 58
IS 2
BP 171
EP 177
DI 10.1080/01635580701328339
PG 7
WC Oncology; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Nutrition & Dietetics
GA 204RK
UT WOS:000249061500006
PM 17640163
DA 2022-11-30
ER

PT J
AU Wu, WC
   Lai, CC
   Liu, JH
   Singh, T
   Li, LM
   Peumans, WJ
   Van Damme, EJM
   Wu, AM
AF Wu, Wei-Chi
   Lai, Chi-Chun
   Liu, Jia-Hau
   Singh, Tanuja
   Li, Lien-Ming
   Peumans, Willy J.
   Van Damme, Els J. M.
   Wu, Albert M.
TI Differential binding to glycotopes among the layers of three mammalian
   retinal neurons by man-containing N-linked glycan, T-alpha (Gal beta
   1-3GalNAc alpha 1-), Tn (GalNAc alpha 1-Ser/Thr) and I-beta/II beta (Gal
   beta 1-3/4GlcNAc beta-) reactive lectins
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE carbohydrate; disaccharide structural units; lectins; retina
ID INTERPHOTORECEPTOR MATRIX PROTEOGLYCANS; PHOTORECEPTOR CELLS;
   PIGMENT-EPITHELIUM; CONE; LOCALIZATION; RETINOBLASTOMA; GLYCOPROTEINS;
   DEGENERATION
AB Carbohydrate structures between retinal neurons and retinal pigment epithelium (RPE) play an important role in maintaining the integrity of retinal adhesion to underlying RPE, and in retinal detachment pathogenesis. Since relevant knowledge is still in the primary stage, glycotopes on the adult retina of mongrel canines (dog), micropigs and Sprague-Dawley rats were examined by lectino-histochemistry, using a panel of 16 different lectins. Paraffin sections of eyes were stained with biotinylated lectins, and visualized by streptavidin-peroxidase and diaminobenzidine staining. Mapping the affinity profiles, it is concluded that: (i) all sections of the retina reacted well with Morniga M, suggesting that N-linked glycans are present in all layers of the retina; (ii) no detectable human blood group ABH active glycotopes were found among retinal layers; (iii) outer and inner segments contained glycoconjugates rich in ligands reacting with T-alpha (Gal beta 1-3GalNAc alpha 1-Ser/Thr) and Tn (GalNAc alpha 1-Ser/Thr) specific lectins; (iv) cone cells of retina specifically bound peanut agglutinin (PNA), which recognizes T (alpha) residues and could be used as a specific marker for these photoreceptors; (v) the retinas of rat, dog and pig, had a similar binding profile but with different intensity; (vi) each retinal layer had its own binding characteristic. This information may provide useful background knowledge for normal retinal physiology and miscellaneous retinal diseases, including retinal detachment (RD) and age-related macular degeneration (ARMD).
C1 Chang Gung Univ, Inst Mol & Cellular Biol, Glycoimmunochem Res Lab, Tao Yuan, Kwei San, Taiwan.
   Chang Gung Mem Hosp, Dept Ophthalmol, Tao Yuan, Taiwan.
   Univ Ghent, Fac Biolsci Engn, Dept Mol Biotechnol, B-9000 Ghent, Belgium.
C3 Chang Gung University; Chang Gung Memorial Hospital; Ghent University
RP Wu, AM (通讯作者)，Chang Gung Univ, Inst Mol & Cellular Biol, Glycoimmunochem Res Lab, 333, Tao Yuan, Kwei San, Taiwan.
EM amwu@mail.cgu.edu.tw
RI Van Damme, Els J/B-4410-2015; Van Damme, Els/U-3904-2019
OI Van Damme, Els/0000-0001-9848-766X; Lai, Chi-Chun/0000-0001-9547-7212
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NR 38
TC 4
Z9 4
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
EI 1573-6903
J9 NEUROCHEM RES
JI Neurochem. Res.
PD MAY
PY 2006
VL 31
IS 5
BP 619
EP 628
DI 10.1007/s11064-006-9060-8
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 053AV
UT WOS:000238276800006
PM 16770733
DA 2022-11-30
ER

PT J
AU Fan, BJ
   Tam, POS
   Choy, KW
   Wang, DY
   Lam, DSC
   Pang, CP
AF Fan, BJ
   Tam, POS
   Choy, KW
   Wang, DY
   Lam, DSC
   Pang, CP
TI Molecular diagnostics of genetic eye diseases
SO CLINICAL BIOCHEMISTRY
LA English
DT Review
DE genetic eye disease; genetic testing; molecular diagnostic service
ID OPEN-ANGLE GLAUCOMA; COMPLEMENT FACTOR-H; PRIMARY CONGENITAL GLAUCOMA;
   AGE-RELATED MACULOPATHY; BETA-INDUCED FACTOR; RETINITIS-PIGMENTOSA;
   CYTOCHROME P4501B1; APOLIPOPROTEIN-E; OCULAR GENETICS; MYOCILIN GENE
AB Eye diseases can be simple or complex, and mostly of heterogeneous molecular genetics. Some eye diseases are caused by mutations in a single gene, but some diseases, such as primary open angle glaucoma, can be due to sequence variations in multiple genes. In some diseases, both genetic and epigenetic mechanisms are involved, as was recently revealed in the mechanism of retinoblastoma. Disease causative mutations and phenotypes may vary by ethnicity and geography. To date, more than a hundred candidate genes for eye diseases are known, although less than 20 have definite disease-causing mutations. The three common genetic eye diseases, primary open angle glaucoma, age-related macular degeneration, and retinitis pigmentosa, all have known gene mutations, but these account for only a portion of the patients. While the search for eye disease genes and mutations still goes on, known mutations have been utilized for diagnosis. Genetic markers for presymptomatic and pre-natal diagnosis are available for specific diseases such as primary open angle glaucoma and retinoblastoma. This paper reviews the molecular basis of common genetic eye diseases and the available genetic markers for clinical diagnosis. Difficulties and challenges in molecular investigation of some eye diseases are discussed. Establishment of ethnic-specific disease databases that contain both clinical and genetic information for identification of genetic markers with diagnostic, prognostic, or pharmacological value is strongly advocated. (C) 2005 The Canadian Society of Clinical Chemists. All rights reserved.
C1 Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, Kowloon, Hong Kong, Peoples R China.
   Chinese Univ Hong Kong, Dept Obstet & Gynecol, Hong Kong, Hong Kong, Peoples R China.
C3 Chinese University of Hong Kong; Chinese University of Hong Kong
RP Pang, CP (通讯作者)，Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, 147K Argyle St, Kowloon, Hong Kong, Peoples R China.
EM cppang@cuhk.edu.hk
RI Choy, Richard/AAW-8230-2020; Lam, Dennis/AAL-1211-2020; Pang, Chi
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OI Choy, Richard/0000-0002-3616-6200; Fan, Baojian/0000-0002-6851-2737
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NR 105
TC 24
Z9 29
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0009-9120
EI 1873-2933
J9 CLIN BIOCHEM
JI Clin. Biochem.
PD MAR
PY 2006
VL 39
IS 3
BP 231
EP 239
DI 10.1016/j.clinbiochem.2005.11.010
PG 9
WC Medical Laboratory Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Medical Laboratory Technology
GA 029MW
UT WOS:000236568300008
PM 16412407
DA 2022-11-30
ER

PT J
AU Cai, BC
   Zhang, Z
   Sun, S
   Lin, TT
   Ke, YF
   Li, ZQ
   Yang, J
   Li, XR
AF Cai, Bincui
   Zhang, Zhe
   Sun, Shuo
   Lin, Tingting
   Ke, Yifeng
   Li, Zhiqing
   Yang, Jin
   Li, Xiaorong
TI A Pilot Application of an iTRAQ-Based Proteomics Screen Estimates the
   Effects of Cigarette Smokers' Serum on RPE Cells With AMD High-Risk
   Alleles
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE age-related macular degeneration; cigarette smoking; iTRAQ proteomics;
   ARMS2; HTRA1
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; OXIDATIVE STRESS;
   ASSOCIATION; POLYMORPHISMS; EXPOSURE; HTRA1; ARMS2
AB Purpose: The aim of this study was to explore whether there are interactions between genetic (ARMS2/HTRA1) and environmental factors (cigarette smoking) in the pathogenesis of age-related macular degeneration (AMD). Methods: Primary human retinal pigment epithelial (hRPE) cells were obtained from four donors' eyes with AMD high-risk ARMS2/HTRA1 alleles, and two donors' eyes with wild-type alleles were used as controls. The pooled serum from 32 smokers and 35 nonsmokers were collected and used separately to treat hRPE cells. The isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics was used to identify associated proteins and comparing the differences between AMD high-risk and low-risk HTRA1/ARMS2 alleles after exposure to smokers' serum. Results: After stimulation with the smokers'serum, 400 differentially expressed proteins (DEPs) were detected in the high-risk allele cells. Several DEPs are involved in neuronal protein degeneration and oxidative stress pathways. The smokers' serum stimulation or HTRA1 overexpression can both upregulate caveolin-1, which was one of the DEPs. Besides, the smokers' serum enhanced the phagocytosis of cultured human RPE cells. Conclusions: The study confirmed the AMD high-risk alleles, HTRA1, and cigarette smoking can promote AMD development by regulating caveolin-1 expression. Translational Relevance: AMD high-risk alleles and environmental risk factors can promote the occurrence and development of AMD by regulating caveolin-1 expression, upregulation of which will induce apoptotic cell death in response to cellular stress in early AMD conditions.
C1 [Cai, Bincui; Zhang, Zhe; Sun, Shuo; Lin, Tingting; Ke, Yifeng; Li, Zhiqing; Yang, Jin; Li, Xiaorong] Tianjin Med Univ, Tianjin Int Joint Res & Dev Ctr Ophthalmol & Vis, Tianjin Key Lab Retinal Funct & Dis, Eye Inst,Eye Hosp, Tianjin, Peoples R China.
   [Cai, Bincui; Zhang, Zhe; Sun, Shuo; Lin, Tingting; Ke, Yifeng; Li, Zhiqing; Yang, Jin; Li, Xiaorong] Tianjin Med Univ, Sch Optometry, Eye Hosp, Tianjin, Peoples R China.
   [Zhang, Zhe] Fudan Univ, Eye & ENT Hosp, NHC Key Lab Myopia, Eye Inst, Shanghai, Peoples R China.
   [Zhang, Zhe] Fudan Univ, Eye & ENT Hosp, NHC Key Lab Myopia, Dept Ophthalmol, Shanghai, Peoples R China.
   [Zhang, Zhe] Chinese Acad Med Sci, Shanghai Res Ctr Ophthalmol & Optometry, Key Lab Myopia, Shanghai, Peoples R China.
C3 Tianjin Medical University; Tianjin Medical University; Fudan
   University; Fudan University; Chinese Academy of Medical Sciences -
   Peking Union Medical College
RP Yang, J; Li, XR (通讯作者)，Tianjin Med Univ, Ophthalmol Res Inst, Eye Hosp, 251 Fukang Rd, Tianjin 300384, Peoples R China.
EM yangjin-324@163.com; xiaorli@163.com
FU National Natural Science Foundation of China [81400412, 81570872,
   81500745, 81670875]; Natural Science Foundation of Tianjin City
   [17JCYBJC27200, 18JCQNJC10700]; Henry Norman Bethune: LangMuYoung
   Scientist scholarship [BJ-LM2015008L]
FX Supported by the National Natural Science Foundation of China
   (81670875); Natural Science Foundation of Tianjin City (18JCQNJC10700);
   Natural Science Foundation of Tianjin City (17JCYBJC27200); a grant of
   the Henry Norman Bethune: LangMuYoung Scientist scholarship
   (BJ-LM2015008L); National Natural Science Foundation of China (81400412;
   81570872; and 81500745).
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NR 26
TC 0
Z9 0
U1 0
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 FEB
PY 2022
VL 11
IS 2
BP 1
EP 13
DI 10.1167/tvst.11.2.15
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZP4AA
UT WOS:000766365000001
PM 35138344
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Gao, SX
   Zheng, XH
   Wu, JH
AF Gao, Shunxiang
   Zheng, Xin
   Wu, Jihong
TI A biolayer interferometry-based enzyme-linked aptamer sorbent assay for
   real-time and highly sensitive detection of PDGF-BB
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Aptamer; PDGF-BB; Biolayer interferometry; Enzyme-linked aptamer sorbent
   assay
ID GROWTH-FACTOR-BB; THERAPEUTIC TARGET; LIGANDS; AMPLIFICATION; MOLECULES;
   BIOSENSOR; SYSTEM; CANCER; HYBRIDIZATION; ANTIBODIES
AB Accurate, fast and sensitive detection of disease-specific protein biomarkers, especially in blood, urine, or other bodily fluids, is an important approach to achieve early disease diagnosis. Platelet-derived growth factor-BB (PDGF-BB), a widely used biomarker, is involved in a substantial number of serious diseases, such as hepatic fibrosis, atherosclerosis, age-related macular degeneration and diabetic eye disease and is often over-expressed in human malignant tumors. Therefore, the development of sensitive and specific detection methods for PDGF-BB is of great importance for the early diagnosis of disease and assessments of patient recovery. In the current study, a biolayer interferometry-based enzyme-linked aptamer sorbent assay (BLI-ELASA) was successfully established for rapid (20-25 min), high-throughput (8 or 16 samples) and real-time monitoring of PDGF-BB in clinical samples. The method exhibited a broad detection range from 0.5 to 1000 ng/mL of PDGF-BB (good linear range from 0.5 to 10 ng/mL), with a low detection limit of 0.08 ng/mL. Moreover, BLI-ELASA was applied to the detection of PDGF-BB in spiked serum and urine samples and showed a high degree of selectivity for PDGF-BB, good reproducibility, and stability. We believe that the methodology in this work can be easily adapted to detect other biomolecules in clinical samples, including viruses, pathogens and toxins, in a rapid, sensitive, high throughput and real-time manner.
C1 [Gao, Shunxiang; Wu, Jihong] Fudan Univ, Eye Inst, Eye & ENT Hosp, Coll Med, Shanghai, Peoples R China.
   [Gao, Shunxiang; Wu, Jihong] Sci & Technol Commiss Shanghai Municipal, Shanghai Key Lab Visual Impairment & Restorat, Shanghai, Peoples R China.
   [Gao, Shunxiang; Wu, Jihong] Minist Hlth, Key Lab Myopia, Shanghai, Peoples R China.
   [Zheng, Xin] Second Mil Med Univ, Changhai Hosp, Dept Lab Diag, Shanghai, Peoples R China.
C3 Fudan University; Science & Technology Commission of Shanghai
   Municipality (STCSM); Naval Medical University
RP Wu, JH (通讯作者)，Fudan Univ, Eye Inst, Eye & ENT Hosp, Coll Med, Shanghai, Peoples R China.
EM jihongwu@fudan.edu.cn
OI Gao, Shunxiang/0000-0001-5267-6289
FU National Natural Science Foundation of China [81700883, 81702094,
   81770925, 81470624]; National Program on Key Basic Research Project of
   China [2013CB967503]; Western Medicine Leader Program of Shanghai
   Municipal Science and Technology Commission [17411971700]
FX This work was supported by National Natural Science Foundation of China
   (81700883, 81702094, 81770925 and 81470624), the National Program on Key
   Basic Research Project of China (2013CB967503), and the Western Medicine
   Leader Program of Shanghai Municipal Science and Technology Commission
   (17411971700).
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NR 41
TC 24
Z9 24
U1 6
U2 159
PU ELSEVIER ADVANCED TECHNOLOGY
PI OXFORD
PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON,
   OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-5663
EI 1873-4235
J9 BIOSENS BIOELECTRON
JI Biosens. Bioelectron.
PD APR 15
PY 2018
VL 102
BP 57
EP 62
DI 10.1016/j.bios.2017.11.017
PG 6
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
   Electrochemistry; Nanoscience & Nanotechnology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
   Electrochemistry; Science & Technology - Other Topics
GA FU9LE
UT WOS:000424176600008
PM 29125972
DA 2022-11-30
ER

PT J
AU Kim, J
   Lee, YM
   Jung, W
   Park, SB
   Kim, CS
   Kim, JS
AF Kim, Junghyun
   Lee, Yun Mi
   Jung, Wookwon
   Park, Su-Bin
   Kim, Chan-Sik
   Kim, Jin Sook
TI Aster koraiensis Extract and Chlorogenic Acid Inhibit Retinal
   Angiogenesis in a Mouse Model of Oxygen-Induced Retinopathy
SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; CHOROIDAL
   NEOVASCULARIZATION; INTRAVITREAL INJECTION; IN-VITRO; VEGF;
   ENDOPHTHALMITIS; IDENTIFICATION; ANTIOXIDANT; MECHANISMS
AB Aster koraiensis extract (AKE) is a standard dietary herbal supplement. Chlorogenic acid (CA) is the major compound present in AKE. Retinal neovascularization is a common pathophysiology of retinopathy of prematurity, diabetic retinopathy, and wet form age-related macular degeneration. In this study, we aimed to evaluate the effects of AKE and CA on retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Vascular endothelial growth factor-(VEGF-) induced tube formation was assayed in human vascular endothelial cells. Experimental retinal neovascularization was induced by exposing C57BL/6 mice to 75% oxygen on postnatal day 7 (P7) and then returning them to normal oxygen pressure on P12. AKE (25 and 50 mg/kg/day) and CA (25 and 50 mg/kg/day) were administered intraperitoneally for 5 days (P12-P16). Retinal flat mounts were prepared to measure the extent of retinal neovascularization at P17. The incubation of human vascular endothelial cells with AKE and CA (1-10 mu g/mL)the extent of retinal neovascularization at P17. The incubation of human vascular endothelial cells with AKE and CA (1-10 mu g/mL) resulted in the inhibition of VEGF-mediated tube formation in a dose-dependent manner. The neovascular area was significantly smaller in AKE or CA-treated mice than in the vehicle-treated mice. These results suggest that AKE is a potent antiangiogenic agent and that its antiangiogenic activity may, in part, be attributable to the bioactive component CA.
C1 [Kim, Junghyun; Lee, Yun Mi; Kim, Chan-Sik; Kim, Jin Sook] Korea Inst Oriental Med, Korean Med Convergence Res Div, Daejeon, South Korea.
   [Kim, Junghyun; Jung, Wookwon; Park, Su-Bin] Chonbuk Natl Univ, Sch Dent, Dept Oral Pathol, Jeonju 54896, South Korea.
C3 Korea Institute of Oriental Medicine (KIOM); Jeonbuk National University
RP Kim, CS; Kim, JS (通讯作者)，Korea Inst Oriental Med, Korean Med Convergence Res Div, Daejeon, South Korea.
EM chskim@kiom.re.kr; jskim@kiom.re.kr
FU Korea Institute of Planning and Evaluation for Technology in Food,
   Agriculture, Forestry and Fisheries (IPET) - Ministry of Agriculture,
   Food and Rural Affairs [316023-05-2-CG000]; Korea Institute of Oriental
   Medicine [K17270]
FX This research was supported by the Korea Institute of Planning and
   Evaluation for Technology in Food, Agriculture, Forestry and Fisheries
   (IPET) funded by the Ministry of Agriculture, Food and Rural Affairs
   (316023-05-2-CG000) and the Korea Institute of Oriental Medicine
   (K17270).
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Z9 5
U1 0
U2 2
PU HINDAWI LTD
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PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1741-427X
EI 1741-4288
J9 EVID-BASED COMPL ALT
JI Evid.-based Complement Altern. Med.
PY 2018
VL 2018
AR 6402650
DI 10.1155/2018/6402650
PG 8
WC Integrative & Complementary Medicine
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Integrative & Complementary Medicine
GA GE9UF
UT WOS:000431575400001
PM 29849715
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Kilic, R
   Karagoz, N
   Cetin, AB
   Cakmak, Y
   Sezer, H
   Ozay, Y
   Comcali, SU
   Dursun, A
AF Kilic, Rasit
   Karagoz, Naim
   Cetin, Abdi Bahadir
   Cakmak, Yasin
   Sezer, Hafize
   Ozay, Yusuf
   Comcali, Sebile Ustun
   Dursun, Ayhan
TI The prevalence of exfoliation syndrome in Turkey
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE cataract; coronary artery disease; exfoliation syndrome; glaucoma
ID OPEN-ANGLE GLAUCOMA; PSEUDOEXFOLIATION SYNDROME; POPULATION; FREQUENCY;
   MORTALITY; DISEASE; RISK; EYE
AB Purpose: To investigate the prevalence of the exfoliation syndrome and its relationship with ocular and cardiovascular diseases in the Central Anatolia region of Turkey.
   Methods: This cross-sectional and population-based study was conducted at the Sivas Province among the population aged 40 years and over. The diagnosis of XFS was made when exfoliative material was found on the anterior lens capsule or iris on slit-lamp examination. The subjects were divided into an XFS group and a non-XFS group according to the presence of exfoliative material, and the groups were compared for the presence of glaucoma, cataract, age-related macular degeneration, phacodonesis, hypertension, diabetes mellitus, coronary artery disease, smoking and alcohol-use frequency.
   Results: XFS was present in 63 subjects consisting of 42 males (8.0%) and 21 females (3.6%) for an overall rate of 5.7% (95% CI: 0.054-0.060). Once we adjusted the values for age, we found a statistically significant relationship of increased age and male gender with the presence of XFS (p = 0.001, p = 0.027, respectively). The relationship between XFS and glaucoma, cataract and phacodonesis was found to be statistically significant (p = 0.001). No relationship was found between exfoliation syndrome and hypertension, diabetes mellitus and coronary artery disease.
   Conclusion: The prevalence of exfoliation syndrome was 5.7% in this population-based study. There was a statistically significant relationship between XFS and advancing age and male gender.
C1 [Kilic, Rasit; Cetin, Abdi Bahadir; Cakmak, Yasin; Ozay, Yusuf; Comcali, Sebile Ustun] Sivas Numune Hosp, Dept Ophthalmol, Sivas, Turkey.
   [Karagoz, Naim] Cumhuriyet Univ, Fac Med, Dept Med Educ, Sivas, Turkey.
   [Sezer, Hafize] Cumhuriyet Univ, Fac Med, Dept Biostat, Sivas, Turkey.
   [Dursun, Ayhan] Cumhuriyet Univ, Fac Med, Dept Ophthalmol, Sivas, Turkey.
C3 Sivas Numune Hospital; Cumhuriyet University; Cumhuriyet University;
   Cumhuriyet University
RP Kilic, R (通讯作者)，Ahi Evran Univ, Fac Med, Dept Ophthalmol, Kirsehir, Turkey.
EM kilicrasit@gmail.com
RI Karagöz, Naim/GVT-9824-2022; Kılıç, Raşit/AAP-6844-2021
OI Kilic, Rasit/0000-0001-6671-9067
FU Sivas Provincial Management of Public Health; Sivas Association of
   Public Hospitals Management
FX We thank the Sivas Provincial Management of Public Health and Sivas
   Association of Public Hospitals Management for their support of the
   study.
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NR 34
TC 6
Z9 6
U1 0
U2 7
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 MAR
PY 2016
VL 94
IS 2
BP E105
EP E108
DI 10.1111/aos.12885
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DE9KR
UT WOS:000370956800004
PM 26508674
OA Bronze
DA 2022-11-30
ER

PT J
AU Song, JH
   Kim, YH
   Lee, SC
   Kim, MH
   Lee, JH
AF Song, Ji Hun
   Kim, Yong Hyun
   Lee, Sung Chul
   Kim, Min Ho
   Lee, Ji Hwan
TI Inhibitory Effect of Chrysin (5,7-Dihydroxyflavone) on Experimental
   Choroidal Neovascularization in Rats
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Chrysin; Fluorescein angiography; Intravitreal injection; Laser-induced
   choroidal neovascularization
ID GROWTH-FACTOR; MACULAR DEGENERATION; CELL-PROLIFERATION; DIETARY
   FLAVONOIDS; EXPRESSION; OVEREXPRESSION; RANIBIZUMAB; PREVENTION; THERAPY
AB Purpose: The aim of this study was to evaluate the effect of chrysin on laser-induced experimental choroidal neovascularization (CNV) in a rat model. Methods: Male brown Norway rats were anesthetized, and a diode laser was used to break Bruch's membrane. One week later, each rat was intravitreally injected with 5 mu l of 15 mg/ml chrysin, and CNV development was determined by fluorescein angiography at 2 weeks. The effect of chrysin on experimental CNV was assessed by fluorescein angiography and histology. Results: Two weeks after laser treatment, the intensity of fluorescein leakage from the photocoagulated lesions decreased significantly compared with the control group (p = 0.044). When the lesions were categorized into low- and high-leakage groups, there was a significant correlation between chrysin treatment and degree of leakage (p = 0.028). Compared with the chrysin-treated group, the relative risk of developing high-leakage lesions in the control group was 3.18. The mean CNV thickness was significantly thinner in chrysin-treated eyes than in control eyes (34.13 +/- 0.88 vs. 37.76 +/- 0.90 mu m, p = 0.005). Conclusion: Chrysin has an inhibitory effect on CNV in an experimental rat model, indicating that chrysin should be further evaluated for its potential as a therapy for CNV in age-related macular degeneration and in other vision-threatening conditions associated with CNV. (C) 2016 S. Karger AG, Basel
C1 [Song, Ji Hun; Kim, Yong Hyun] Ajou Univ, Sch Med, Dept Ophthalmol, San 5, Suwon 443721, South Korea.
   [Song, Ji Hun; Lee, Sung Chul] Yonsei Univ, Coll Med, Grad Sch, Dept Med, Seoul, South Korea.
   [Lee, Sung Chul; Lee, Ji Hwan] Yonsei Univ, Coll Med, Dept Ophthalmol, Inst Vis Res, Seoul, South Korea.
   [Kim, Min Ho] Armed Forces Cent Hosp, Dept Ophthalmol, Songnam, South Korea.
C3 Ajou University; Yonsei University; Yonsei University Health System;
   Yonsei University; Yonsei University Health System
RP Song, JH (通讯作者)，Ajou Univ, Sch Med, Dept Ophthalmol, San 5, Suwon 443721, South Korea.
EM dreyesong@naver.com
OI Lee, Ji Hwan/0000-0003-1759-8195; , Sung Chul/0000-0001-9438-2385
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NR 35
TC 9
Z9 9
U1 0
U2 2
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2016
VL 56
IS 1
BP 49
EP 55
DI 10.1159/000444929
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DN1FR
UT WOS:000376812200008
PM 27058958
DA 2022-11-30
ER

PT J
AU Suzuki, M
   Curcio, CA
   Mullins, RF
   Spaide, RF
AF Suzuki, Mihoko
   Curcio, Christine A.
   Mullins, Robert F.
   Spaide, Richard F.
TI REFRACTILE DRUSEN Clinical Imaging and Candidate Histology
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE drusen; geographic atrophy; histology
ID MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; ELECTRON-MICROSCOPY; DONOR
   EYES; DEPOSITS; CALCIUM; ASSEMBLIES
AB Purpose: To evaluate eyes with refractile drusen using clinical imaging and to identify candidate histologic correlates of refractile drusen.
   Methods: Refractile drusen were defined as drusenoid material containing small refractile spherules. Retrospective analysis of color, autofluorescence, and spectral domain optical coherence tomography images of eyes with refractile drusen was performed to characterize the morphology and topography of these lesions. Macular sections from donor eyes were processed with a von Kossa stain for calcium phosphate and viewed by light microscopy. Punches of retinal pigment epithelium-choroid from donors with geographic atrophy were prepared for transmission electron microscopy.
   Results: Fundus findings of 14 eyes of 10 patients with age-related macular degeneration (age, 82.9 +/- 5.6 years) were evaluated. A generalized loss of autofluorescence signal over refractile drusen appeared to spread over a larger area than each druse, for drusen located centrally. By color fundus photography, refractile drusen showed corresponding depigmentation around drusen that were located in the center of the macula. Optical coherence tomography imaging of refractile drusen showed hyperreflective dots. In the histologic specimens, drusen contained many small spherules rich in calcium phosphate. Ultrastructural examination of the spherules showed complex assemblies consisting of concentric shells containing thin layers of calcium.
   Conclusion: Refractile drusen appear to be a stage of drusen regression marked by loss of retinal pigment epithelium, thus contributing to the development of geographic atrophy. Calcium-containing spherules appear to account for the glistening appearance.
C1 [Suzuki, Mihoko; Spaide, Richard F.] Vitreous Retina Macula Consultants New York, New York, NY 10022 USA.
   [Suzuki, Mihoko; Spaide, Richard F.] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA.
   [Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL 35294 USA.
   [Mullins, Robert F.] Univ Iowa, Wynn Inst Vis Res, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
C3 Vitreous Retina Macula Consultants of New York; Manhattan Eye Ear &
   Throat Hospital; University of Alabama System; University of Alabama
   Birmingham; University of Iowa
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; Mullins, Robert F/I-6717-2013
OI Mullins, Robert/0000-0002-5006-0891
FU LuEsther T. Mertz Retinal Research Foundation; NEI [EY06109]; NIH
   [EY024605, EY016822]
FX Supported by the LuEsther T. Mertz Retinal Research Foundation. C. A.
   Curcio is supported by NEI EY06109 with institutional support from the
   EyeSight Foundation of Alabama and Research to Prevent Blindness Inc. R.
   F. Mullins is supported by NIH EY024605 and EY016822.
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NR 22
TC 35
Z9 35
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 MAY
PY 2015
VL 35
IS 5
BP 859
EP 865
DI 10.1097/IAE.0000000000000503
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CG6KI
UT WOS:000353408900004
PM 25768253
DA 2022-11-30
ER

PT J
AU Jo, EH
   Lee, GY
   Cho, SJ
   Yoo, H
   Kim, OY
   Seong, K
   Kang, YS
   Lee, D
   Khang, G
AF Jo, Eun Hye
   Lee, Ga Young
   Cho, Su Jin
   Yoo, Hanna
   Kim, On You
   Seong, Kyeongyeol
   Kang, Young Sun
   Lee, Dongwon
   Khang, Gilson
TI ATTACHMENT AND PROLIFERATION OF RETINAL PIGMENT EPITHELIAL CELLS ON
   SMALL INTESTINE SUBMUCOSA POWDER IMPREGNATED
   POLY(L-LACTIDE-CO-GLYCOLIDE) FILM
SO BIOMEDICAL ENGINEERING-APPLICATIONS BASIS COMMUNICATIONS
LA English
DT Article
DE Small intestine submucosa; Retinal pigment epithelium;
   Poly(lactic-co-glycolic acid)
ID TISSUE ENGINEERED BONE; SCHWANN-CELL; SIS SPONGE; SCAFFOLDS; CULTURE;
   TRANSPLANTATION; MICROSPHERES; REGENERATION; SURFACE; SHEETS
AB The retinal pigment epithelium (RPE) closely interacts with photoreceptors in the maintenance of visual function. The native RPEs exist as a monolayer structure and have a mottled brown color due to the presence of melanin and other pigments including lipofuscin granules, which accumulate with age. In age-related macular degeneration (AMD), RPE's dysfunction and changes in Bruch's membrane occur. Thus, small intestine submucosa/poly(lactic-co-glycolic acid) (SIS/PLGA) film is a biomimetic transplant consisting of a layer of healthy RPE cells cultured on a support membrane. The goals of this study were to evaluate the effects of attachment and proliferation of RPEs on SIS/PLGA films. Porcine SIS is an acellular tissue and widely used as a biomaterial without immunorejection responses, whereas PLGA is a biodegradable synthetic polymer with acceptable mechanical strength and well-controlled degradation rate. We fabricated SIS/PLGA films using 20 wt% of SIS. We measured MTT to confirm cellular adhesion of cell number attached on film at 1, 3, 5, and 7 days. Morphology of cellular adhesion on films was confirmed by scanning electron microscopy at 1, 3, and 7 days. Further, reverse transcription polymerase chain reaction (RT-PCR) was conducted to confirm messenger RNA expression of RPE65 as RPE's marker and expression of cytokeratin, and RPE65 were determined by AEC immunocytochemical staining. These results suggest that SIS provides suitable surface to RPEs.
C1 [Jo, Eun Hye; Lee, Ga Young; Cho, Su Jin; Yoo, Hanna; Kim, On You; Seong, Kyeongyeol; Lee, Dongwon; Khang, Gilson] Chonbuk Natl Univ, Dept BIN Fus Technol, Dept Polymer Nano Sci & Technol, Jeonju 561756, South Korea.
   [Jo, Eun Hye; Lee, Ga Young; Cho, Su Jin; Yoo, Hanna; Kim, On You; Seong, Kyeongyeol; Lee, Dongwon; Khang, Gilson] Chonbuk Natl Univ, Polymer Fus Res Ctr, Jeonju 561756, South Korea.
   [Kang, Young Sun] Konkuk Univ, Inst Biomed Sci & Technol, Seoul, South Korea.
C3 Jeonbuk National University; Jeonbuk National University; Konkuk
   University
RP Lee, D (通讯作者)，Chonbuk Natl Univ, Dept BIN Fus Technol, Dept Polymer Nano Sci & Technol, 664-14 Dukjin, Jeonju 561756, South Korea.
EM dlee@jbnu.ac.kr; gskhang@jbnu.ac.kr
RI Khang, Gilson/B-2109-2013
FU SCRC [SC4110]; WCU [R31-20029]; KRF [2008-314-D00115]
FX This research was supported by SCRC (SC4110), WCU (R31-20029), and KRF
   (2008-314-D00115).
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NR 27
TC 2
Z9 2
U1 1
U2 23
PU WORLD SCIENTIFIC PUBL CO PTE LTD
PI SINGAPORE
PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE
SN 1016-2372
EI 1793-7132
J9 BIOMED ENG-APP BAS C
JI Biomed. Eng.-Appl. Basis Commun.
PD APR
PY 2011
VL 23
IS 2
BP 119
EP 126
DI 10.4015/S1016237211002438
PG 8
WC Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA 757QG
UT WOS:000290102200005
DA 2022-11-30
ER

PT J
AU Nakao, S
   Noda, K
   Zandi, S
   Sun, DW
   Taher, M
   Schering, A
   Xie, F
   Mashima, Y
   Hafezi-Moghadam, A
AF Nakao, Shintaro
   Noda, Kousuke
   Zandi, Souska
   Sun, Dawei
   Taher, Mandi
   Schering, Alexander
   Xie, Fang
   Mashima, Yukihiko
   Hafezi-Moghadam, Ali
TI VAP-1 Mediated M2 Macrophage Infiltration Underlies IL-1 beta- but Not
   VEGF-A-Induced Lymph- and Angiogenesis
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID VASCULAR ADHESION PROTEIN-1; ENDOTHELIAL INJURY; IN-VIVO;
   LYMPHANGIOGENESIS; SELECTIN; NEOVASCULARIZATION; INFLAMMATION;
   MECHANISM; CELLS
AB Vascular adhesion protein-1 (YAP-1) contributes to inflammatory and angiogenic diseases, including cancer and age-related macular degeneration. It is expressed in blood vessels and contributes to inflammatory leukocyte recruitment. The cytokines IL-1 beta and vascular endothelial growth factor A (VEGF-A) modulate angiogenesis, lymphangiogenesis, and leukocyte infiltration. The lymphatic endothelium expresses intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, which facilitate leukocyte transmigration into the lymphatic vessels. However, whether lymphatics express YAP-1 and whether they contribute to cytokine-dependent lymph- and angiogenesis are unknown. We investigated the role of VAP-1 in IL-1 beta- and VEGF-A-induced lymph- and angiogenesis using the established corneal tnicropocket assay. IL-1 beta increased YAP-1 expression in the inflamed cornea. Our in vivo molecular imaging revealed significantly higher YAP-1 expression in neovasculature than in the preexisting vessels. YAP-1 was expressed in blood but not lymphatic vessels in vivo. IL-1 beta-induced M2 macrophage infiltration and lymph- and angiogenesis were blocked by YAP-1 inhibition. In contrast, VEGF-A-induced lymph- and angiogenesis were unaffected by YAP-1 inhibition. Our results indicate a key role for YAP-1 in lymph- and angiogenesis-related macrophage recruitment. YAP-1 might become a new target for treatment of inflammatory lymph- and angiogenic diseases, including cancer. (Am J Pathol 2011, 178:1913-1921; DOI: 10.1016/j.ajpath.2011.01.011)
C1 [Hafezi-Moghadam, Ali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Excellence Funct & Mol Imaging, Boston, MA 02115 USA.
   [Nakao, Shintaro; Noda, Kousuke; Zandi, Souska; Sun, Dawei; Taher, Mandi; Schering, Alexander; Xie, Fang; Hafezi-Moghadam, Ali] Harvard Univ, Angiogenesis Lab, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
   [Nakao, Shintaro; Noda, Kousuke; Zandi, Souska; Sun, Dawei; Taher, Mandi; Schering, Alexander; Xie, Fang; Hafezi-Moghadam, Ali] Harvard Univ, Dept Ophthalmol, Sch Med, Boston, MA 02115 USA.
   [Zandi, Souska; Sun, Dawei; Taher, Mandi; Schering, Alexander; Xie, Fang; Hafezi-Moghadam, Ali] Harvard Univ, Dept Radiol, Sch Med, Boston, MA 02115 USA.
   [Mashima, Yukihiko] R Tech Ueno Ltd, Tokyo, Japan.
C3 Harvard University; Brigham & Women's Hospital; Harvard Medical School;
   Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Harvard University; Harvard Medical School; Harvard
   University; Harvard Medical School
RP Hafezi-Moghadam, A (通讯作者)，Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Excellence Funct & Mol Imaging, 221 Longwood Ave,3rd Floor, Boston, MA 02115 USA.
EM ahm@bwh.harvard.edu
OI Hafezi-Moghadam, Ali/0000-0002-5336-0697; Zandi,
   Souska/0000-0001-9351-4278
FU National Institutes of Health [AI050775]; Malaysian Palm Oil Board;
   American Health Assistance Foundation; Bausch Lomb; Japan Eye Bank
   Association; Tear Film & Ocular Surface Society
FX Supported by National Institutes of Health grant AI050775, the Malaysian
   Palm Oil Board, American Health Assistance Foundation, an overseas
   Research Fellowship Award from Bausch & Lomb, a Fellowship Award from
   the Japan Eye Bank Association, and Tear Film & Ocular Surface Society
   Young Investigator Fellowship (to S.N. under the mentorship of A.H.-M.).
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   Noda K, 2009, EXP EYE RES, V89, P774, DOI 10.1016/j.exer.2009.07.010
   Roca H, 2009, J BIOL CHEM, V284, P34342, DOI 10.1074/jbc.M109.042671
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NR 28
TC 37
Z9 40
U1 0
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD APR
PY 2011
VL 178
IS 4
BP 1913
EP 1921
DI 10.1016/j.ajpath.2011.01.011
PG 9
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 865JH
UT WOS:000298306700047
PM 21435467
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Chang, LK
   Sarraf, D
AF Chang, Louis K.
   Sarraf, David
TI Tears of the retinal pigment epithelium - An old problem in a new era
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Review
ID OPTICAL COHERENCE TOMOGRAPHY; INDOCYANINE GREEN VIDEOANGIOGRAPHY;
   INTRAVITREAL BEVACIZUMAB AVASTIN; CHOROIDAL NEOVASCULARIZATION;
   PHOTODYNAMIC THERAPY; PATHOGENESIS; DETACHMENT; PEGAPTANIB; INJECTION;
   SIGN
AB Background/Purpose: Recent attention has focused upon several reports of retinal pigment epithelium (RPE) tears following vascular endothelial growth factor (VEGF)-modulating therapy. The authors review the clinical features, etiologies, imaging characteristics, and pathogenesis of RPE tears and their relationship with intravitreal anti-VEGF treatments.
   Methods: The authors conducted a comprehensive literature search of RPE tears or rips of any etiology using the PubMed database. They have also included a retrospective analysis of an additional five cases of RPE tears following anti-VEGF therapy, four after bevacizumab and one after ranibizumab.
   Results: Thirty-three cases of RPE tear after treatment with pegaptanib, bevacizumab, or ranibizumab have been previously reported in the literature. The authors have collected and analyzed the clinical features for 25 of these cases for which this information was available. The authors have also included analysis of an additional five cases. Common features of each of these 30 cases included advanced age of the patient, the presence of fibrovascular pigment epithelial detachment (PED) or PED associated with choroidal neovascularization (CN\, and diagnosis of the tear within 4 to 8 weeks of the first or second injection.
   Conclusions: RPE tears may develop during the course of anti-VEGF therapy for age-related macular degeneration-related PED. Patients with high-risk lesions, especially large irregular PED associated with CNV, should be counseled and monitored for this complication, which may limit visual prognosis.
C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   Kaiser Permanente, Dept Ophthalmol, Woodland Hills, CA USA.
   Martin Luther King Jr Harbor Med Ctr, Dept Ophthalmol, Los Angeles, CA USA.
   Greater LA VA Healthcare Ctr, Dept Ophthalmol, Los Angeles, CA USA.
C3 University of California System; University of California Los Angeles;
   Kaiser Permanente; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center
RP Sarraf, D (通讯作者)，Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, 100 Stein Plaza, Los Angeles, CA 90095 USA.
EM dsarraf@ucla.edu
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NR 67
TC 115
Z9 126
U1 0
U2 5
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 JUN
PY 2007
VL 27
IS 5
BP 523
EP 534
DI 10.1097/IAE.0b013e3180a032db
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 178ZP
UT WOS:000247259400001
PM 17558312
DA 2022-11-30
ER

PT J
AU Groux, K
   Verschueren, A
   Nanteau, C
   Clemencon, M
   Fink, M
   Sahel, JA
   Boccara, C
   Paques, M
   Reichman, S
   Grieve, K
AF Groux, Kassandra
   Verschueren, Anna
   Nanteau, Celine
   Clemencon, Marilou
   Fink, Mathias
   Sahel, Jose-Alain
   Boccara, Claude
   Paques, Michel
   Reichman, Sacha
   Grieve, Kate
TI Dynamic full-field optical coherence tomography allows live imaging of
   retinal pigment epithelium stress model
SO COMMUNICATIONS BIOLOGY
LA English
DT Article
ID HUMAN IPS CELLS; APICAL MICROVILLI; MECHANISMS; MIGRATION
AB Dynamic full-field optical coherence tomography (D-FFOCT) is used for live cell imaging of primary porcine retinal pigment epithelium (ppRPE) cultures and human induced pluripotent stem cell-derived RPE (hiRPE) cultures, allowing non-invasive realtime access to organelles and cytoskeleton dynamics in RPE cells.
   Retinal degenerative diseases lead to the blindness of millions of people around the world. In case of age-related macular degeneration (AMD), the atrophy of retinal pigment epithelium (RPE) precedes neural dystrophy. But as crucial as understanding both healthy and pathological RPE cell physiology is for those diseases, no current technique allows subcellular in vivo or in vitro live observation of this critical cell layer. To fill this gap, we propose dynamic full-field OCT (D-FFOCT) as a candidate for live observation of in vitro RPE phenotype. In this way, we monitored primary porcine and human stem cell-derived RPE cells in stress model conditions by performing scratch assays. In this study, we quantified wound healing parameters on the stressed RPE, and observed different cell phenotypes, displayed by the D-FFOCT signal. In order to decipher the subcellular contributions to these dynamic profiles, we performed immunohistochemistry to identify which organelles generate the signal and found mitochondria to be the main contributor to D-FFOCT contrast. Altogether, D-FFOCT appears to be an innovative method to follow degenerative disease evolution and could be an appreciated method in the future for live patient diagnostics and to direct treatment choice.
C1 [Groux, Kassandra; Fink, Mathias; Boccara, Claude] CNRS, ESPCI Paris PSL, Inst Langevin, 10 Rue Vauquelin, F-75005 Paris, France.
   [Groux, Kassandra; Verschueren, Anna; Sahel, Jose-Alain; Paques, Michel; Grieve, Kate] Quinze Vingts Natl Eye Hosp, Paris Eye Imaging Grp, INSERM, CC 1423,DGOS, 28 Rue Charenton, F-75012 Paris, France.
   [Verschueren, Anna; Nanteau, Celine; Clemencon, Marilou; Sahel, Jose-Alain; Reichman, Sacha; Grieve, Kate] Sorbonne Univ, Inst Vis, INSERM, CNRS, 17 Rue Moreau, F-75012 Paris, France.
   [Sahel, Jose-Alain] Fdn Ophtalmol Adolphe Rotschild, Dept Ophthalmol, F-75019 Paris, France.
   [Sahel, Jose-Alain] Univ Pittsburgh, Dept Ophthalmol, Sch Med, Pittsburgh, PA 15213 USA.
C3 Centre National de la Recherche Scientifique (CNRS); UDICE-French
   Research Universities; PSL Research University Paris; Ecole Superieure
   de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI);
   Universite Paris Cite; CHNO des Quinze-Vingts; Institut National de la
   Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite; Centre National de la Recherche
   Scientifique (CNRS); Institut National de la Sante et de la Recherche
   Medicale (Inserm); UDICE-French Research Universities; Sorbonne
   Universite; Universite Paris Cite; Pennsylvania Commonwealth System of
   Higher Education (PCSHE); University of Pittsburgh
RP Groux, K (通讯作者)，CNRS, ESPCI Paris PSL, Inst Langevin, 10 Rue Vauquelin, F-75005 Paris, France.; Groux, K; Grieve, K (通讯作者)，Quinze Vingts Natl Eye Hosp, Paris Eye Imaging Grp, INSERM, CC 1423,DGOS, 28 Rue Charenton, F-75012 Paris, France.; Grieve, K (通讯作者)，Sorbonne Univ, Inst Vis, INSERM, CNRS, 17 Rue Moreau, F-75012 Paris, France.
EM kassandra.groux@gmail.com; kategrieve@gmail.com
RI Fink, Mathias/M-9437-2016; Reichman, Sacha/R-7581-2017
OI Fink, Mathias/0000-0002-8494-7562; Reichman, Sacha/0000-0003-1776-6339;
   GROUX, Kassandra/0000-0001-6697-3778
FU OREO [ANR-19-CE19-0023]; IHU FOReSIGHT [ANR-18-IAHU-0001]; HELMHOLTZ
   (European Research Council (ERC)) [610110]; OPTORETINA (European
   Research Council (ERC)) [101001841]; LabEx LIFESENSES
   [ANR-10-LABX-0065]; Institut Carnot Fondation Voir et Entendre,
   RETINIT-iPS [ANR-19-CE18-0005]; LabEx WIFI [ANR-10-LABX-0024]
FX The authors would like to thank Valerie Forster for providing primary
   porcine samples. The authors thank Jules Scholler, Pedro Mece and
   Olivier Thouvenin for fruitful discussions on the results. The authors
   thank Marie Darche and Leyna Boucherit for their help in
   immunohistochemistry experiments and analysis of results. The authors
   would like to thank the direction and management teams of the
   institutions involved. The authors thank the following sources of
   funding: OREO [ANR-19-CE19-0023], IHU FOReSIGHT [ANR-18-IAHU-0001],
   HELMHOLTZ (European Research Council (ERC) (#610110)), OPTORETINA
   (European Research Council (ERC) (#101001841)), LabEx LIFESENSES
   [ANR-10-LABX-0065], Institut Carnot Fondation Voir et Entendre,
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PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
EI 2399-3642
J9 COMMUN BIOL
JI Commun. Biol.
PD JUN 10
PY 2022
VL 5
IS 1
AR 575
DI 10.1038/s42003-022-03479-6
PG 11
WC Biology; Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other
   Topics
GA 2A2ZI
UT WOS:000809375300003
PM 35688936
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Naidorf-Rosenblatt, H
   Landau-Part, D
   Moisseiev, J
   Alhalel, A
   Huna-Baron, R
   Skaat, A
   Pilus, S
   Levi, L
   Leshno, A
AF Naidorf-Rosenblatt, Hadar
   Landau-Part, Daphna
   Moisseiev, Joseph
   Alhalel, Amir
   Huna-Baron, Ruth
   Skaat, Alon
   Pilus, Sima
   Levi, Lior
   Leshno, Ari
TI OCULAR SURFACE TEMPERATURE DIFFERENCES IN RETINAL VASCULAR DISEASES
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE ocular surface temperature; diabetic retinopathy; age-related macular
   degeneration; thermography; diabetic macular edema
ID DIABETIC-RETINOPATHY; MACULAR-DEGENERATION; THERMOGRAPHY; COMPLEX; EYES
AB Purpose: To define the effect of age-related macular degeneration (AMD) and diabetic retinopathy (DR) on the ocular thermographic profile.
   Methods: This retrospective cross-sectional study included subjects diagnosed with DR or AMD between January and April 2019. Individuals without ocular disease served as controls. A thermal imaging camera was used for ocular surface temperature (OST) acquisition. The mean temperatures of the medial cantus, lateral cantus, and cornea were calculated.
   Results: Thermographic images were obtained from 133 subjects (260 eyes, 97 DR and 163 AMD) and 48 controls (55 eyes). Ocular surface temperature was higher among patients with AMD and lowest among patients with DR (P < 0.001). A subgroup analysis revealed that eyes with diabetic macular edema had significantly higher OSTs than DR eyes without diabetic macular edema. Moreover, the OST in eyes with diabetic macular edema was similar to the measurements of the AMD group. There were no differences in OSTs between neovascular and nonneovascular AMD eyes.
   Conclusion: Although AMD and DR are considered posterior segment conditions, their effect on OST implies that the entire globe is involved. Although both conditions result from similar multifactorial pathophysiologic changes, the differences in OST between DR and AMD might be due to dissimilarity in the balance of pathologic processes involved in each condition. Further research is required to better understand the pathophysiology of these diseases and their effect on OST as well as to determine the effect of vasculature, circulation, and tissue metabolism on ocular temperature.
C1 [Naidorf-Rosenblatt, Hadar; Landau-Part, Daphna; Moisseiev, Joseph; Alhalel, Amir; Huna-Baron, Ruth; Skaat, Alon; Pilus, Sima; Levi, Lior; Leshno, Ari] Tel Aviv Univ, Sackler Fac Med, Sheba Med Ctr, Goldschleger Eye Inst, Tel Aviv, Israel.
   [Landau-Part, Daphna; Leshno, Ari] Sheba Talpiot Med Leadership Program, Tel Aviv, Israel.
C3 Chaim Sheba Medical Center; Tel Aviv University; Sackler Faculty of
   Medicine
RP Naidorf-Rosenblatt, H (通讯作者)，Tel Aviv Univ, Sackler Fac Med, Sheba Med Ctr, Goldschleger Eye Inst, Tel Aviv, Israel.; Naidorf-Rosenblatt, H (通讯作者)，Sheba Med Ctr, Goldschleger Eye Inst, Tel Hashomer, Israel.
EM arileshno@g-mail.com
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NR 30
TC 4
Z9 4
U1 2
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 JAN
PY 2022
VL 42
IS 1
BP 152
EP 158
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA XS3RA
UT WOS:000732829100028
PM 34369439
DA 2022-11-30
ER

PT J
AU Du, JH
   Zhu, SY
   Lim, RR
   Chao, JR
AF Du, Jianhai
   Zhu, Siyan
   Lim, Rayne R.
   Chao, Jennifer R.
TI Proline metabolism and transport in retinal health and disease
SO AMINO ACIDS
LA English
DT Review
DE Proline; Metabolism; Transport; Retina; Retinal pigment epithelium;
   Retinal disease
ID SUBTYPE
AB The retina is one of the most energy-demanding tissues in the human body. Photoreceptors in the outer retina rely on nutrient support from the neighboring retinal pigment epithelium (RPE), a monolayer of epithelial cells that separate the retina and choroidal blood supply. RPE dysfunction or cell death can result in photoreceptor degeneration, leading to blindness in retinal degenerative diseases including some inherited retinal degenerations and age-related macular degeneration (AMD). In addition to having ready access to rich nutrients from blood, the RPE is also supplied with lactate from adjacent photoreceptors. Moreover, RPE can phagocytose lipid-rich outer segments for degradation and recycling on a daily basis. Recent studies show RPE cells prefer proline as a major metabolic substrate, and they are highly enriched for the proline transporter, SLC6A20. In contrast, dysfunctional or poorly differentiated RPE fails to utilize proline. RPE uses proline to fuel mitochondrial metabolism, synthesize amino acids, build the extracellular matrix, fight against oxidative stress, and sustain differentiation. Remarkably, the neural retina rarely imports proline directly, but it uptakes and utilizes intermediates and amino acids derived from proline catabolism in the RPE. Mutations of genes in proline metabolism are associated with retinal degenerative diseases, and proline supplementation is reported to improve RPE-initiated vision loss. This review will cover proline metabolism in RPE and highlight the importance of proline transport and utilization in maintaining retinal metabolism and health.
C1 [Du, Jianhai; Zhu, Siyan] West Virginia Univ, Dept Ophthalmol & Visual Sci, Morgantown, WV 26506 USA.
   [Du, Jianhai; Zhu, Siyan] West Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA.
   [Lim, Rayne R.; Chao, Jennifer R.] Univ Washington, Dept Ophthalmol, Seattle, WA 98109 USA.
   [Du, Jianhai] WVU Eye Inst, One Med Ctr Dr,POB 9193, Morgantown, WV 26505 USA.
C3 West Virginia University; West Virginia University; University of
   Washington; University of Washington Seattle
RP Du, JH (通讯作者)，West Virginia Univ, Dept Ophthalmol & Visual Sci, Morgantown, WV 26506 USA.; Du, JH (通讯作者)，West Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA.; Du, JH (通讯作者)，WVU Eye Inst, One Med Ctr Dr,POB 9193, Morgantown, WV 26505 USA.
EM jianhai.du@hsc.wvu.edu
OI Chao, Jennifer/0000-0002-6859-5552; Du, Jianhai/0000-0002-2019-8128
FU National Institutes of Health [EY026030, EY031324]; BrightFocus
   Foundation [M2020141, M2020217]; Research for Prevention of Blindness;
   Alcon Research Institute; Retina Research Foundation
FX National Institutes of Health Grant EY026030 (JRC and JD) and EY031324
   (JD), BrightFocus Foundation M2020141 (JD) and M2020217 (JRC), Research
   for Prevention of Blindness (JRC), Alcon Research Institute (JRC) and
   the Retina Research Foundation (JD) supported this work. We are grateful
   to Dr. James B. Hurley for his critical reading of the manuscript.
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NR 184
TC 11
Z9 11
U1 0
U2 5
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD DEC
PY 2021
VL 53
IS 12
SI SI
BP 1789
EP 1806
DI 10.1007/s00726-021-02981-1
EA APR 2021
PG 18
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA XL7PD
UT WOS:000641190500001
PM 33871679
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Almarhoun, M
   Biswas, L
   Alhasani, RH
   Wong, A
   Tchivelekete, GM
   Zhou, XZ
   Patterson, S
   Bartholomew, C
   Shu, XH
AF Almarhoun, Mohammad
   Biswas, Lincoln
   Alhasani, Reem Hasaballah
   Wong, Aileen
   Tchivelekete, Gabriel Mbuta
   Zhou, Xinzhi
   Patterson, Steven
   Bartholomew, Chris
   Shu, Xinhua
TI Overexpression of STARD3 attenuates oxidized LDL-induced oxidative
   stress and inflammation in retinal pigment epithelial cells
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Article
DE Age-related macular degeneration; STARD3; Retinal pigment epithelial
   cells; Cholesterol efflux; Oxidized low density lipoprotein
ID PROTEIN-PROTEIN INTERACTIONS; CHOLESTEROL TRANSPORT; MACULAR
   DEGENERATION; NLRP3 INFLAMMASOME; EFFLUX; MLN64; MECHANISMS; DOMAIN;
   TSPO
AB Age-related macular degeneration (AMD) is the most common cause of visual disorder in aged people and may lead to complete blindness with ageing. The major clinical feature of AMD is the presence of cholesterol enriched deposits underneath the retinal pigment epithelium (RPE) cells. The deposits can induce oxidative stress and inflammation. It has been suggested that abnormal cholesterol homeostasis contributes to the pathogenesis of AMD. However, the functional role of defective cholesterol homeostasis in AMD remains elusive. STARD proteins are a family of proteins that contain a steroidogenic acute regulatory protein-related lipid transfer domain. There are fifteen STARD proteins in mammals and some, such as STARD3, are responsible for cholesterol trafficking. Previously there was no study of STARD proteins in retinal cholesterol metabolism and trafficking. Here we examined expression of the Stard3 gene in mouse retinal and RPE cells at ages of 2 and 20 months. We found that expression of Stard 3 gene transcripts in both mouse RPE and retina was significantly decreased at age of 20 months when compared to that of age 2 months old. We created a stable ARPE-19 cell line overexpressing STARD3 and found this resulted in increased cholesterol efflux, reduced accumulation of intracellular oxidized LDL, increased antioxidant capacity and lower levels of inflammatory cytokines. The data suggested that STARD3 is a potential target for AMD through promoting the removal of intracellular cholesterol and slowing the disease progression.
C1 [Almarhoun, Mohammad; Biswas, Lincoln; Alhasani, Reem Hasaballah; Wong, Aileen; Tchivelekete, Gabriel Mbuta; Zhou, Xinzhi; Patterson, Steven; Bartholomew, Chris; Shu, Xinhua] Glasgow Caledonian Univ, Dept Biol & Biomed Sci, Glasgow G4 0BA, Lanark, Scotland.
   [Shu, Xinhua] Glasgow Caledonian Univ, Dept Vis Sci, Glasgow G4 0BA, Lanark, Scotland.
   [Shu, Xinhua] Shaoyang Univ, Sch Basic Med Sci, Shaoyang 422000, Hunan, Peoples R China.
   [Alhasani, Reem Hasaballah] Umm Al Qura Univ, Fac Appl Sci, Dept Biol, Mecca, Saudi Arabia.
C3 Glasgow Caledonian University; Glasgow Caledonian University; Shaoyang
   University; Umm Al Qura University
RP Shu, XH (通讯作者)，Glasgow Caledonian Univ, Dept Biol & Biomed Sci, Glasgow G4 0BA, Lanark, Scotland.
EM Xinhua.Shu@gcu.ac.uk
FU Kuwait Government; Rosetrees Trust [M160, M160-F1, M160-F2]; National
   Eye Research Centre [SAC037]; Tenovus Scotland [S20-02]; Lotus
   Scholarship Program of Hunan Province (2019)
FX This work was supported by a PhD scholarship from Kuwait Government, the
   Rosetrees Trust (M160, M160-F1, M160-F2), National Eye Research Centre
   (SAC037), Tenovus Scotland (S20-02) and the Lotus Scholarship Program of
   Hunan Province (2019). X.S. is a visiting Professor to Shaoyang
   University.
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NR 43
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 1388-1981
EI 1879-2618
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD JUL
PY 2021
VL 1866
IS 7
AR 158927
DI 10.1016/j.bbalip.2021.158927
EA MAR 2021
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA RV7RZ
UT WOS:000646027100005
PM 33771709
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Baselius, NJH
   Brynskov, T
   Falk, MK
   Sorensen, TL
   Subhi, Y
AF Herlov Baselius, Nanna Jo
   Brynskov, Troels
   Falk, Mads Kruger
   Sorensen, Torben Lykke
   Subhi, Yousif
TI Driving vision in patients with neovascular AMD in anti-VEGF treatment
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age&#8208; related macular degeneration; anti&#8208; VEGF; driver&#8217;
   s license; driving vision
ID MACULAR DEGENERATION
AB Purpose To report real-world experiences on driving vision in patients with neovascular age-related macular degeneration (AMD) undergoing intravitreal anti-VEGF treatment.
   Methods Retrospective cohort study of treatment-naive patients with neovascular AMD commenced in anti-VEGF treatment (n = 416) and followed for 4 years in a pro re nata treatment regimen. Monocular best-corrected visual acuity (BCVA) measured using ETDRS was performed on the treatment eye at all visits and on the fellow eye at baseline, every 6 months, and upon any patient-reported change in vision. Driving vision was defined as BCVA in the best-seeing eye of >= 70 ETDRS letters (equivalent to >= 0.5 Snellen) corresponding to the minimum BCVA required in many countries.
   Results Driving vision was present in 280 patients (67%) and was sustained in 86%, 74%, 65% and 59% of the patients at 1, 2, 3 and 4 years, respectively. Lower BCVA in the best-seeing eye predicted loss of driving vision. In patients without driving vision at baseline, driving vision was regained in 29%, 36%, 39% and 41% of the patients at 1, 2, 3 and 4 years, respectively; but only 35% sustained driving vision after the first year. Lower age and higher BCVA in best-seeing eye predicted regain of driving vision.
   Conclusion Driving vision can be sustained in the majority of the patients if they have driving vision at baseline. This study provides important prognostic information for patients with neovascular AMD.
C1 [Herlov Baselius, Nanna Jo; Brynskov, Troels; Falk, Mads Kruger; Sorensen, Torben Lykke; Subhi, Yousif] Zealand Univ Hosp, Dept Ophthalmol, Vestermarksvej 23, DK-4000 Roskilde, Denmark.
   [Sorensen, Torben Lykke] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
   [Subhi, Yousif] Rigshosp Glostrup, Dept Ophthalmol, Glostrup, Denmark.
C3 University of Copenhagen
RP Subhi, Y (通讯作者)，Zealand Univ Hosp, Dept Ophthalmol, Vestermarksvej 23, DK-4000 Roskilde, Denmark.
EM ysubhi@gmail.com
RI Subhi, Yousif/ABG-6330-2020
OI Subhi, Yousif/0000-0001-6620-5365
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NR 18
TC 1
Z9 1
U1 0
U2 2
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 DEC
PY 2021
VL 99
IS 8
BP E1360
EP E1365
DI 10.1111/aos.14831
EA MAR 2021
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WW9GS
UT WOS:000625397700001
PM 33666364
DA 2022-11-30
ER

PT J
AU Komaromy, AM
   Koehl, KL
   Park, SA
AF Komaromy, Andras M.
   Koehl, Kristin L.
   Park, Shin Ae
TI Looking into the future: Gene and cell therapies for glaucoma
SO VETERINARY OPHTHALMOLOGY
LA English
DT Review
DE cell therapy; gene therapy; glaucoma; intraocular pressure (IOP);
   neuroprotection; ocular biomechanics
ID RETINAL GANGLION-CELLS; HUMAN TRABECULAR MESHWORK; 0.005-PERCENT
   LATANOPROST SOLUTION; ADENOVIRUS-MEDIATED EXPRESSION; INDUCED OCULAR
   HYPERTENSION; DOMINANT-NEGATIVE RHOA; TISSUE GROWTH-FACTOR; OPEN-ANGLE
   GLAUCOMA; OPTIC-NERVE DAMAGE; INTRAOCULAR-PRESSURE
AB Glaucoma is a complex group of optic neuropathies that affects both humans and animals. Intraocular pressure (IOP) elevation is a major risk factor that results in the loss of retinal ganglion cells (RGCs) and their axons. Currently, lowering IOP by medical and surgical methods is the only approved treatment for primary glaucoma, but there is no cure, and vision loss often progresses despite therapy. Recent technologic advances provide us with a better understanding of disease mechanisms and risk factors; this will permit earlier diagnosis of glaucoma and initiation of therapy sooner and more effectively. Gene and cell therapies are well suited to target these mechanisms specifically with the potential to achieve a lasting therapeutic effect. Much progress has been made in laboratory settings to develop these novel therapies for the eye. Gene and cell therapies have already been translated into clinical application for some inherited retinal dystrophies and age-related macular degeneration (AMD). Except for the intravitreal application of ciliary neurotrophic factor (CNTF) by encapsulated cell technology for RGC neuroprotection, there has been no other clinical translation of gene and cell therapies for glaucoma so far. Possible application of gene and cell therapies consists of long-term IOP control via increased aqueous humor drainage, including inhibition of fibrosis following filtration surgery, RGC neuroprotection and neuroregeneration, modification of ocular biomechanics for improved IOP tolerance, and inhibition of inflammation and neovascularization to prevent the development of some forms of secondary glaucoma.
C1 [Komaromy, Andras M.; Koehl, Kristin L.; Park, Shin Ae] Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA.
   [Park, Shin Ae] Purdue Univ, Coll Vet Med, W Lafayette, IN 47907 USA.
C3 Michigan State University; Purdue University System; Purdue University;
   Purdue University West Lafayette Campus
RP Komaromy, AM (通讯作者)，Michigan State Univ, Vet Med Ctr, 736 Wilson Rd,Room D-208, E Lansing, MI 48824 USA.
EM komaromy@msu.edu
OI Park, Shin Ae/0000-0003-3128-2760
FU Michigan State University College of Veterinary Medicine Endowed
   Research Funds; BrightFocus Foundation [G2017185]; National Eye
   Institute [K08EY030950, R01-EY025752]
FX Michigan State University College of Veterinary Medicine Endowed
   Research Funds; BrightFocus Foundation, Grant/Award Number: G2017185;
   National Eye Institute, Grant/Award Number: K08EY030950 and R01-EY025752
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NR 245
TC 7
Z9 9
U1 1
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1463-5216
EI 1463-5224
J9 VET OPHTHALMOL
JI Vet. Ophthalmol.
PD MAR
PY 2021
VL 24
SU 1
SI SI
BP 16
EP 33
DI 10.1111/vop.12858
EA JAN 2021
PG 18
WC Veterinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Veterinary Sciences
GA QY9XS
UT WOS:000605450600001
PM 33411993
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Hurst, J
   Fietz, A
   Tsai, T
   Joachim, SC
   Schnichels, S
AF Hurst, Jose
   Fietz, Agnes
   Tsai, Teresa
   Joachim, Stephanie C.
   Schnichels, Sven
TI Organ Cultures for Retinal Diseases
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Review
DE ex vivo; retinal organ culture; age-related macular degeneration;
   glaucoma; retinitis pigmentosa; central artery occlusion
ID OXIDATIVE STRESS; OCULAR HYPERTENSION; DOWN-REGULATION; GANGLION-CELLS;
   BOVINE RETINA; MOUSE MODEL; STEM-CELLS; IN-VITRO; DEGENERATION; TOXICITY
AB The successful development of novel therapies is closely linked with understanding the underlying pathomechanisms of a disease. To do so, model systems that reflect human diseases and allow for the evaluation of new therapeutic approaches are needed. Yet, preclinical animal studies often have limited success in predicting human physiology, pathology, and therapeutic responses. Moreover, animal testing is facing increasing ethical and bureaucratic hurdles, while human cell cultures are limited in their ability to represent in vivo situations due to the lack of the tissue microenvironment, which may alter cellular responses. To overcome these struggles, organ cultures, especially those of complex organs such as the retina, can be used to study physiological reactions to substances or stressors. Human and animal organ cultures are now well established and recognized. This mini-review discusses how retinal organ cultures can be used to preserve tissue architecture more realistically and therefore better represent disease-related changes. It also shows how molecular biological, biochemical, and histological techniques can be combined to investigate how anatomical localization may alter cellular responses. Examples for the use of retinal organ cultures, including models to study age-related macular degeneration (AMD), retinitis pigmentosa (RP), central artery occlusion (CRAO), and glaucoma are presented, and their advantages and disadvantages are discussed. We conclude that organ cultures significantly improve our understanding of complex retinal diseases and may advance treatment testing without the need for animal testing.
C1 [Hurst, Jose; Fietz, Agnes; Schnichels, Sven] Univ Tubingen, Univ Eye Hosp, Ctr Ophthalmol, Tubingen, Germany.
   [Tsai, Teresa; Joachim, Stephanie C.] Ruhr Univ Bochum, Univ Eye Hosp, Expt Eye Res Inst, Bochum, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Ruhr University Bochum
RP Schnichels, S (通讯作者)，Univ Tubingen, Univ Eye Hosp, Ctr Ophthalmol, Tubingen, Germany.
EM sven.schnichels@med.uni-tuebingen.de
RI Joachim, Stephanie/AAV-5980-2021
OI Schnichels, Sven/0000-0002-2385-5517
FU Tubinger Athene-Programm fur Nachwuchs-Wissenschaftlerinnen; Fortune
   Program of the Medical Faculty Tubingen [2543-1-0];
   Forschungsorientierte Gleichstellungsforderung
FX JH acknowledges funding from the Tubinger Athene-Programm fur
   Nachwuchs-Wissenschaftlerinnen and the Forschungsorientierte
   Gleichstellungsforderung. SS acknowledges funding from the Fortune
   Program of the Medical Faculty Tubingen (2543-1-0).
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NR 102
TC 5
Z9 5
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 NOV 25
PY 2020
VL 14
AR 583392
DI 10.3389/fnins.2020.583392
PG 8
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA PB8GO
UT WOS:000596553200001
PM 33324149
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Yang, M
   So, KF
   Lo, ACY
   Lam, WC
AF Yang, Ming
   So, Kwok-Fai
   Lo, Amy Cheuk Yin
   Lam, Wai Ching
TI The Effect ofLycium barbarumPolysaccharides on Pyroptosis-Associated
   Amyloid beta(1-40)Oligomers-Induced Adult Retinal Pigment Epithelium 19
   Cell Damage
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE cell death; drusen; eye disease; retina; traditional Chinese medicine
   (TCM)
ID NLRP3 INFLAMMASOME ACTIVATION; LYCIUM-BARBARUM POLYSACCHARIDES; MACULAR
   DEGENERATION; BETA; DEATH; APOPTOSIS; PROTECTS; MODEL
AB Age-related macular degeneration (AMD) is a sight-threatening disease with limited treatment options. We investigated whether amyloid beta(1-40)(A beta(1-40)) could cause pyroptosis and evaluated the effects ofLycium barbarumpolysaccharides (LBP) on A beta(1-40)oligomers-induced retinal pigment epithelium 19 (ARPE-19) damage, which is an in vitro AMD model. A beta(1-40)oligomers verified by Western blot were added to ARPE-19 cells with or without 24 h LBP treatment. A beta(1-40)oligomers significantly decreased ARPE-19 cell viability with obvious morphological changes under light microscopy. SEM revealed swollen cells with a bubbling appearance and ruptured cell membrane, which are morphological characteristics of pyroptosis. ELISA results showed increased expression of IL-1 beta and IL-18, which are the final products of pyroptosis. LBP administration for 24 h had no toxic effects on ARPE-19 cells and improved cell viability and morphology while disrupting A beta(1-40)oligomerization in a dose-dependent manner. Furthermore, A beta(1-40)oligomers up-regulated the cellular immunoreactivity of pyroptosis markers including NOD-like receptors protein 3 (NLRP3), caspase-1, and membrane N-terminal cleavage product of GSDMD (GSDMD-N), which could be reversed by LBP treatment. Taken together, this study showed that LBP effectively protects the A beta(1-40)oligomers-induced pyroptotic ARPE-19 cell damages by its anti-A beta(1-40)oligomerization properties and its anti-pyroptotic effects.
C1 [Yang, Ming; So, Kwok-Fai; Lo, Amy Cheuk Yin; Lam, Wai Ching] Univ Hong Kong, Li Ka Shing Fac Med, Dept Ophthalmol, Hong Kong, Peoples R China.
   [So, Kwok-Fai] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Peoples R China.
C3 University of Hong Kong; University of Hong Kong
RP Lam, WC (通讯作者)，Univ Hong Kong, Li Ka Shing Fac Med, Dept Ophthalmol, Hong Kong, Peoples R China.
EM hrmeym@hku.hk; hrmaskf@hku.hk; amylo@hku.hk; waichlam@hku.hk
RI Lo, Amy C. Y./C-1195-2009
OI Lo, Amy C. Y./0000-0003-4239-6851
FU Albert Bing-Ching Young Professorship Endowment in Ophthalmology
FX Albert Bing-Ching Young Professorship Endowment in Ophthalmology.
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   Zhang WJ, 2018, ARTIF CELL NANOMED B, V46, P1463, DOI 10.1080/21691401.2017.1373657
NR 50
TC 13
Z9 14
U1 7
U2 21
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 JUL
PY 2020
VL 21
IS 13
AR 4658
DI 10.3390/ijms21134658
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA MM5PO
UT WOS:000550208700001
PM 32629957
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Gu, DV
   Agron, S
   May, LN
   Mirza, RG
   Bryar, PJ
AF Gu, David
   Agron, Samantha
   May, Lauren N.
   Mirza, Rukhsana G.
   Bryar, Paul J.
TI Nonmydriatic Retinal Diabetic Screening in the Primary Care Setting:
   Assessing Degree of Retinopathy and Incidence of Nondiabetic Ocular
   Diagnoses
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE telemedicine; telehealth; ophthalmology; education
ID FUNDUS PHOTOGRAPHY; TELEMEDICINE
AB Purpose: To study the rates and severity of diabetic retinopathy (DR), rates of nondiabetic ocular disease, and rates of referral to eye care providers in the context of nonmydriatic retinal screening performed in primary care and endocrinology clinics.
   Materials and Methods: This study is a retrospective chart review of patients who had nonmydriatic retinal imaging in the primary care setting. Presence and severity of DR as well as detection of nondiabetic ocular diseases were analyzed. Referral rates for different types of pathology were determined.
   Results: A total of 324 patients were imaged and 294 (90.7%) had gradable images. Mild DR was found in at least one eye of 71 (24.1%) patients, moderate in 20 (6.8%), severe in 3 (1.0%), and proliferative DR in 2 (0.6%). Macular edema was found in 13 (4.4%) patients. Nondiabetic ocular diseases were suspected in 106 (36.1%) patients. The most prevalent findings included glaucoma suspect (10.9%), age-related macular degeneration suspect (8.8%), and hypertensive retinopathy (5.4%). Seventy (23.8%) patients were referred to an eye care provider for DR, 66 (22.4%) were referred for nondiabetic eye disease, and 21 (7.1%) were referred for both.
   Conclusion: One-third of patients were found to have some degree of DR. Suspected nondiabetic disease or other pathologies were found in one-third of the study population. Referral for examination by an eye care provider was recommended for approximately half of the patients.
C1 [Gu, David; Agron, Samantha; May, Lauren N.; Mirza, Rukhsana G.; Bryar, Paul J.] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, 645 N Michigan Ave,Suite 440, Chicago, IL 60611 USA.
C3 Northwestern University; Feinberg School of Medicine
RP Bryar, PJ (通讯作者)，Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, 645 N Michigan Ave,Suite 440, Chicago, IL 60611 USA.
EM p-bryar@northwestern.edu
OI Bryar, Paul/0000-0001-8494-3089
CR American Academy of Ophthalmology Retina/Vitreous Panel, 2017, PREF PRACT PATT GUID
   [Anonymous], 2017, DIABETES REPORT CARD
   Bashshur RL, 2015, TELEMED E-HEALTH, V21, P321, DOI 10.1089/tmj.2015.0029
   Eppley SE, 2019, OPHTHALMOLOGY, V126, P1492, DOI 10.1016/j.ophtha.2019.05.033
   Gao X, 2018, TELEMED J E-HEALTH, V25, P802
   Horton MB, 2016, CURR DIABETES REP, V16, DOI 10.1007/s11892-016-0813-8
   Mansberger SL, 2013, TELEMED E-HEALTH, V19, P942, DOI 10.1089/tmj.2012.0313
   Resnikoff S, 2004, B WORLD HEALTH ORGAN, V82, P844
   Silva PS, 2016, JAMA OPHTHALMOL, V134, P330, DOI 10.1001/jamaophthalmol.2015.5605
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   Williams GA, 2004, OPHTHALMOLOGY, V111, P1055, DOI 10.1016/j.ophtha.2004.02.004
NR 11
TC 5
Z9 5
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-5627
EI 1556-3669
J9 TELEMED E-HEALTH
JI Telemed. e-Health
PD OCT 1
PY 2020
VL 26
IS 10
BP 1252
EP 1256
DI 10.1089/tmj.2019.0206
EA FEB 2020
PG 5
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA NW9WV
UT WOS:000515327200001
PM 32083513
DA 2022-11-30
ER

PT J
AU Choi, MJ
   Lee, GW
   Kim, JS
   Kim, HS
   Kim, D
   Song, JE
   Thangavelu, M
   Khang, G
AF Choi, Min Joung
   Lee, Gi Won
   Kim, Jin Su
   Kim, Han Sol
   Kim, David
   Song, Jeong Eun
   Thangavelu, Muthukumar
   Khang, Gilson
TI UV-Irradiated RPE Cells Assist Differentiation of Bone Marrow Derived
   Mesenchymal Stem Cells into RPE Cells Under a Direct Co-Culture
   Environment
SO MACROMOLECULAR RESEARCH
LA English
DT Article
DE RPE; co-culture; BMSC; differentiation; Gellan-gum
ID GELLAN GUM; IN-VITRO; MACULAR DEGENERATION; STROMAL CELLS; HYDROGELS;
   EXPRESSION; SCAFFOLDS
AB Degeneration of retinal pigment epithelium cells (RPE) or delamination of RPE from Bruch's membrane causes visual impairment. While regeneration of RPE cells is desirable to treat age-related macular degeneration (AMD) RPE cells of mammals, which are inherently non-renewable. Here, the bone marrow derived mesenchymal stem cells (BMSCs) that have the advantage of rapid growth and ease of extraction, which are adopted in order to help regenerate RPE cell. By co-culture with RPE cell, BMSCs exhibited a tendency to differentiate into RPE cell. By irradiating with the ultraviolet (UV) light, RPE cell was inhibited from growing and the differentiation of BMSCs was induced. The B-27 (R) supplement was used as a differentiation factor, which helps BMSCs to differentiation into RPE cells. Specifically, B-27 (R) supplement was mixed into the growth medium, which was added only to the co-culture and BMSCs groups. In consequence, UV-irradiated RPE cells did not grow, BMSCs in the co-culture group exhibited a tendency to differentiate into RPE cells. This was demonstrated by MTT assay, SEM, confocal imaging of the live/dead cells, RT-PCR and histological staining. Cell proliferation was the highest in the co-culture group, and the differentiation of BMSCs into RPE cells was observed in RT-PCR and histological staining. Our method will allow BMSCs with B-27 (R) supplement to offer a new direction for RPE regeneration.
C1 [Choi, Min Joung; Lee, Gi Won; Kim, Jin Su; Kim, Han Sol; Kim, David; Song, Jeong Eun; Thangavelu, Muthukumar; Khang, Gilson] Chonbuk Natl Univ, Dept Polymer Nano Sci & Technol, Dept BIN Convergence Technol, Jeonju 54896, Jeonbuk, South Korea.
   [Choi, Min Joung; Lee, Gi Won; Kim, Jin Su; Kim, Han Sol; Kim, David; Song, Jeong Eun; Thangavelu, Muthukumar; Khang, Gilson] Chonbuk Natl Univ, Polymer Mat Fus Res Ctr, Jeonju 54896, Jeonbuk, South Korea.
C3 Jeonbuk National University; Jeonbuk National University
RP Khang, G (通讯作者)，Chonbuk Natl Univ, Dept Polymer Nano Sci & Technol, Dept BIN Convergence Technol, Jeonju 54896, Jeonbuk, South Korea.
EM gskhang@jbnu.ac.kr
RI Thangavelu, Muthukumar/E-3891-2016; song, jeong eun/P-9106-2015
OI Thangavelu, Muthukumar/0000-0002-4449-6015; song, jeong
   eun/0000-0001-6879-7616
FU International Research AMP; Development Program [2017K1A3A7A03089427];
   National Research Foundation of Korea (NRF) - Ministry of Science, ICT
   AMP; Future Planning [2017R1A2B3 010270]
FX This research was supported by the International Research & Development
   Program (2017K1A3A7A03089427) and Basic Science Research Program
   (2017R1A2B3 010270) through the National Research Foundation of Korea
   (NRF) funded by the Ministry of Science, ICT & Future Planning.
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NR 29
TC 0
Z9 0
U1 0
U2 11
PU POLYMER SOC KOREA
PI SEOUL
PA ROOM 601, HATCHON BUILDING, 831 YEOKSAM-DONG, KANGNAM-KU, SEOUL 135-792,
   SOUTH KOREA
SN 1598-5032
EI 2092-7673
J9 MACROMOL RES
JI Macromol. Res.
PD AUG
PY 2019
VL 27
IS 8
BP 781
EP 788
DI 10.1007/s13233-019-7114-4
PG 8
WC Polymer Science
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Polymer Science
GA IS8NP
UT WOS:000482406900007
DA 2022-11-30
ER

PT J
AU Nusinovici, S
   Sabanayagam, C
   Teo, BW
   Tan, GSW
   Wong, TY
AF Nusinovici, Simon
   Sabanayagam, Charumathi
   Teo, Boon Wee
   Tan, Gavin Siew Wei
   Wong, Tien Yin
TI Vision Impairment in CKD Patients: Epidemiology, Mechanisms,
   Differential Diagnoses, and Prevention
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; RETINAL VEIN OCCLUSION; STAGE RENAL-DISEASE;
   SERUM CYSTATIN C; MACULAR DEGENERATION; RISK-FACTORS;
   INTRAOCULAR-PRESSURE; DIABETIC-RETINOPATHY; VISUAL IMPAIRMENT; EYE
   DISEASES
AB Eyes and kidneys have numerous structural, developmental, physiologic, and pathogenic pathways in common, suggesting that many kidney and eye diseases may be interlinked. Studies suggest that the prevalence of eye diseases and vision impairment are higher among persons with end-stage kidney disease and earlier stages of chronic kidney disease (CKD) than in those without. Ocular morbidity in persons with CKD and end-stage kidney disease may be due to the following risk factors: (1) underlying conditions and risk factors for CKD such as diabetes or hypertension, (2) metabolic disorders associated with CKD, (3) uremia and anemia, and (4) CKD treatment. Among the chief eye diseases, diabetic retinopathy and age-related macular degeneration are most consistently associated with CKD. Further research for eye diseases such as glaucoma and cataract is needed to determine their relationships with CKD. Despite the high prevalence and burden of vision impairment among persons with CKD, eye screening in patients with CKD is not currently recommended as standard practice. This review suggests that patients with CKD should be encouraged to undergo a complete eye examination. Furthermore, physicians should be aware that patients undergoing dialysis may develop acute eye problems such as acute glaucoma, and appropriate referral to ophthalmologists should be considered in those with a history of glaucoma or recent ocular surgery. Interdisciplinary collaboration between nephrologists and ophthalmologists will ensure enhanced and appropriate management of patients with CKD.
C1 [Nusinovici, Simon; Sabanayagam, Charumathi; Tan, Gavin Siew Wei; Wong, Tien Yin] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Sabanayagam, Charumathi; Tan, Gavin Siew Wei; Wong, Tien Yin] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
   [Sabanayagam, Charumathi; Tan, Gavin Siew Wei; Wong, Tien Yin] Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
   [Teo, Boon Wee] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; National University of Singapore;
   National University of Singapore
RP Wong, TY (通讯作者)，Singapore Natl Eye Ctr, 11 Third Hosp Ave, Singapore 168751, Singapore.
EM ophwty@nus.edu.sg
RI Teo, Boon Wee/E-4976-2014; Sabanayagam, Charumathi/C-1294-2011; Wong,
   Tien Yin/AAC-9724-2020
OI Teo, Boon Wee/0000-0002-4911-8507; Sabanayagam,
   Charumathi/0000-0002-4042-4719; Wong, Tien Yin/0000-0002-8448-1264
FU Singapore National Medical Research Council [NMRC/OFLCG/001/2017]
FX This work was supported by the Singapore National Medical Research
   Council (NMRC/OFLCG/001/2017).
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NR 129
TC 21
Z9 21
U1 0
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JUN
PY 2019
VL 73
IS 6
BP 846
EP 857
DI 10.1053/j.ajkd.2018.12.047
PG 12
WC Urology & Nephrology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Urology & Nephrology
GA HY8RF
UT WOS:000468407400014
PM 30929852
DA 2022-11-30
ER

PT J
AU Ban, N
   Lee, TJ
   Sene, A
   Choudhary, M
   Lekwuwa, M
   Dong, ZY
   Santeford, A
   Lin, JB
   Malek, G
   Ory, DS
   Apte, RS
AF Ban, Norimitsu
   Lee, Tae Jun
   Sene, Abdoulaye
   Choudhary, Mayur
   Lekwuwa, Michael
   Dong, Zhenyu
   Santeford, Andrea
   Lin, Jonathan B.
   Malek, Goldis
   Ory, Daniel S.
   Apte, Rajendra S.
TI Impaired monocyte cholesterol clearance initiates age-related retinal
   degeneration and vision loss
SO JCI INSIGHT
LA English
DT Article
ID SUBRETINAL DRUSENOID DEPOSITS; BEAVER DAM EYE; MACULAR DEGENERATION;
   RETICULAR PSEUDODRUSEN; CARDIOVASCULAR-DISEASE; GENETIC-VARIANTS;
   DARK-ADAPTATION; RISK-FACTORS; IN-VIVO; MICE
AB Advanced age-related macular degeneration (AMD), the leading cause of blindness among people over 50 years of age, is characterized by atrophic neurodegeneration or pathologic angiogenesis. Early AMD is characterized by extracellular cholesterol-rich deposits underneath the retinal pigment epithelium (RPE) called drusen or in the subretinal space called subretinal drusenoid deposits (SDD) that drive disease progression. However, mechanisms of drusen and SDD biogenesis remain poorly understood. Although human AMD is characterized by abnormalities in cholesterol homeostasis and shares phenotypic features with atherosclerosis, it is unclear whether systemic immunity or local tissue metabolism regulates this homeostasis. Here, we demonstrate that targeted deletion of macrophage cholesterol ABC transporters A1 (ABCA1) and -G1 (ABCG1) leads to age-associated extracellular cholesterol-rich deposits underneath the neurosensory retina similar to SDD seen in early human AMD. These mice also develop impaired dark adaptation, a cardinal feature of RPE cell dysfunction seen in human AMD patients even before central vision is affected. Subretinal deposits in these mice progressively worsen with age, with concomitant accumulation of cholesterol metabolites including several oxysterols and cholesterol esters causing lipotoxicity that manifests as photoreceptor dysfunction and neurodegeneration. These findings suggest that impaired macrophage cholesterol transport initiates several key elements of early human AMD, demonstrating the importance of systemic immunity and aging in promoting disease manifestation. Polymorphisms in genes involved with cholesterol transport and homeostasis are associated with a significantly higher risk of developing AMD, thus making these studies translationally relevant by identifying potential targets for therapy.
C1 [Ban, Norimitsu; Lee, Tae Jun; Sene, Abdoulaye; Dong, Zhenyu; Santeford, Andrea; Lin, Jonathan B.; Apte, Rajendra S.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
   [Choudhary, Mayur; Lekwuwa, Michael; Malek, Goldis] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC USA.
   [Lin, Jonathan B.; Apte, Rajendra S.] Washington Univ, Sch Med, Div Biol & Biomed Sci, Neurosci Grad Program, St Louis, MO USA.
   [Malek, Goldis] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA.
   [Ory, Daniel S.] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO USA.
   [Apte, Rajendra S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Apte, Rajendra S.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Duke University; Washington University
   (WUSTL); Duke University; Washington University (WUSTL); Washington
   University (WUSTL); Washington University (WUSTL)
RP Apte, RS (通讯作者)，Ctr Outpatient Hlth, 4901 Forest Pk Ave,6th Floor, St Louis, MO 63108 USA.
EM apte@wustl.edu
RI Choudhary, Mayur/AAU-3497-2021
OI Choudhary, Mayur/0000-0001-8056-011X; Lee, Tae Jun/0000-0003-2699-2573;
   Santeford, Andrea/0000-0002-7691-6213; Malek, Goldis/0000-0003-0026-2388
FU NIH [R01 EY019287, P30 EY02687, R01 EY027802, P30 EY005722];
   International Retinal Research Foundation; Starr Foundation; Carl
   Marshall Reeves and Mildred Almen Reeves Foundation; Bill and Emily
   Kuzma Family Gift for retinal research; Research to Prevent Blindness;
   Jeffrey Fort Innovation Fund; Thome Foundation; Department of
   Ophthalmology and Visual Sciences of Washington University School of
   Medicine; Washington University in St. Louis Medical Scientist Training
   Program (NIH) [T32 GM07200]; Washington University in St. Louis
   Institute of Clinical and Translational Sciences (NIH) [UL1 TR002345,
   TL1 TR002344, P30 DK020579]; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL
   SCIENCES [TL1TR000449, UL1TR002345, TL1TR002344] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [P30EY002687, R01EY027802, P30EY005722,
   R01EY019287] Funding Source: NIH RePORTER; NATIONAL HEART, LUNG, AND
   BLOOD INSTITUTE [R01HL067773] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK056341,
   P30DK020579] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL
   MEDICAL SCIENCES [T32GM007200] Funding Source: NIH RePORTER
FX We thank Wandy L. Beatty for EM analyses. This work was supported by NIH
   grants R01 EY019287 (RSA), P30 EY02687 (Vision Core Grant), R01 EY027802
   (GM), P30 EY005722 (to the Duke Eye Center); the International Retinal
   Research Foundation (NB); the Starr Foundation (RSA); the Carl Marshall
   Reeves and Mildred Almen Reeves Foundation (RSA); the Bill and Emily
   Kuzma Family Gift for retinal research (RSA); a Physician-Scientist
   Award and a Nelson Trust Award from Research to Prevent Blindness (RSA);
   the Jeffrey Fort Innovation Fund (RSA); and the Thome Foundation (RSA).
   Additional funding came from unrestricted grants to the Department of
   Ophthalmology and Visual Sciences of Washington University School of
   Medicine and to the Duke Eye Center, from Research to Prevent Blindness.
   JBL was supported by the Washington University in St. Louis Medical
   Scientist Training Program (NIH grant T32 GM07200) and the Washington
   University in St. Louis Institute of Clinical and Translational Sciences
   (NIH grants UL1 TR002345, TL1 TR002344). Lipidomics was performed in the
   Washington University Metabolomics Facility supported by NIH grant P30
   DK020579.
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NR 33
TC 27
Z9 28
U1 0
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD SEP 6
PY 2018
VL 3
IS 17
AR e120824
DI 10.1172/jci.insight.120824
PG 12
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA GS7KU
UT WOS:000443880600008
PM 30185655
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Ma, B
   Jing, M
   Villalta, PW
   Kapphahn, RJ
   Montezuma, SR
   Ferrington, DA
   Stepanov, I
AF Ma, Bin
   Jing, Meng
   Villalta, Peter W.
   Kapphahn, Rebecca J.
   Montezuma, Sandra R.
   Ferrington, Deborah A.
   Stepanov, Irina
TI Simultaneous determination of 8-oxo-2 '-deoxyguanosine and 8-oxo-2
   '-deoxyadenosine in human retinal DNA by liquid chromatography
   nanoelectrospray-tandem mass spectrometry
SO SCIENTIFIC REPORTS
LA English
DT Article
ID SOLID-PHASE EXTRACTION; MITOCHONDRIAL-DNA; OXIDATIVE DAMAGE; MACULAR
   DEGENERATION; HUMAN-CELLS; 8-OXO-7,8-DIHYDRO-2'-DEOXYGUANOSINE;
   8-HYDROXY-2'-DEOXYGUANOSINE; MUTAGENESIS; SIGNALS; SAMPLES
AB Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. Oxidative damage to mitochondrial DNA (mtDNA) in the retinal pigment epithelium (RPE) may play a key role in AMD. Measurement of oxidative DNA lesions such as 8-oxo-2'-deoxyguanosine (8-oxo-dG) and 8-oxo-2'-deoxyadenosine (8-oxo-dA) in diseased RPE could provide important insights into the mechanism of AMD development. We have developed a liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry method for simultaneous analysis of 8-oxo-dG and 8-oxo-dA in human retinal DNA. The developed method was applied to the analysis of retinal DNA from 5 donors with AMD and 5 control donors without AMD. In mtDNA, the levels of 8-oxo-dG in controls and AMD donors averaged 170 and 188, and 8-oxo-dA averaged 11 and 17 adducts per 10(6) bases, respectively. In nuclear DNA, the levels of 8-oxo-dG in controls and AMD donors averaged 0.54 and 0.96, and 8-oxo-dA averaged 0.04 and 0.05 adducts per 10(6) bases, respectively. This highly sensitive method allows for the measurement of both adducts in very small amounts of DNA and can be used in future studies investigating the pathophysiological role of 8-oxo-dG and 8-oxo-dA in AMD and other oxidative damage-related diseases in humans.
C1 [Ma, Bin; Jing, Meng; Villalta, Peter W.; Stepanov, Irina] Univ Minnesota, Masonic Canc Ctr, Mayo Mail Code 806,420 Delaware St SE, Minneapolis, MN 55455 USA.
   [Kapphahn, Rebecca J.; Montezuma, Sandra R.; Ferrington, Deborah A.] Univ Minnesota, Dept Ophthalmol & Visual Neurosci, Mayo Mail Code 493,420 Delaware St SE, Minneapolis, MN 55455 USA.
   [Stepanov, Irina] Univ Minnesota, Div Environm Hlth Sci, Mayo Mail Code 807,420 Delaware St SE, Minneapolis, MN 55455 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities;
   University of Minnesota System; University of Minnesota Twin Cities;
   University of Minnesota System; University of Minnesota Twin Cities
RP Stepanov, I (通讯作者)，Univ Minnesota, Masonic Canc Ctr, Mayo Mail Code 806,420 Delaware St SE, Minneapolis, MN 55455 USA.; Stepanov, I (通讯作者)，Univ Minnesota, Div Environm Hlth Sci, Mayo Mail Code 807,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM stepa011@umn.edu
RI Villalta, Peter W/J-4091-2019
OI Ferrington, Deborah/0000-0003-2561-7464; Villalta,
   Peter/0000-0002-0067-3083; Stepanov, Irina/0000-0001-5140-8944
FU Masonic Cancer Center, University of Minnesota via NCI grant [P30
   CA077598]; Minnesota Masonic Charities; University of Minnesota Academic
   Health Center - Faculty Development Award; Arnold and Mabel Beckman
   Initiative for Macular Research; Research to Prevent Blindness; NCI
   [CA-77598]; NATIONAL CANCER INSTITUTE [P30CA077598] Funding Source: NIH
   RePORTER
FX We thank Xun Ming for his help with the mass spectrometry analysis; Adam
   Zarth for useful discussions in this study; the Minnesota Lions Eye Bank
   for procuring donor eyes; and Kathy Goode and Sung Lee for photographing
   and processing eye tissue. We also thank Robert Carlson for editorial
   assistance. This study was supported by startup funds to IS from the
   Masonic Cancer Center, University of Minnesota via NCI grant P30
   CA077598 and support from Minnesota Masonic Charities; the University of
   Minnesota Academic Health Center - Faculty Development Award; Arnold and
   Mabel Beckman Initiative for Macular Research; an anonymous benefactor
   for AMD Research; and an unrestricted grant to the Department of
   Ophthalmology and Visual Neurosciences from the Research to Prevent
   Blindness. Mass-spectrometry analyses were carried out in the Analytical
   Biochemistry Shared Resource of the Masonic Cancer Center, supported in
   part by grant CA-77598 from the NCI.
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TC 19
Z9 20
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAR 16
PY 2016
VL 6
AR 22375
DI 10.1038/srep22375
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DG4QP
UT WOS:000372057500001
PM 26979577
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Tammela, T
   Zarkada, G
   Wallgard, E
   Murtomaki, A
   Suchting, S
   Wirzenius, M
   Waltari, M
   Hellstrom, M
   Schomber, T
   Peltonen, R
   Freitas, C
   Duarte, A
   Isoniemi, H
   Laakkonen, P
   Christofori, G
   Yla-Herttuala, S
   Shibuya, M
   Pytowski, B
   Eichmann, A
   Betsholtz, C
   Alitalo, K
AF Tammela, Tuomas
   Zarkada, Georgia
   Wallgard, Elisabet
   Murtomaki, Aino
   Suchting, Steven
   Wirzenius, Maria
   Waltari, Marika
   Hellstrom, Mats
   Schomber, Tibor
   Peltonen, Reetta
   Freitas, Catarina
   Duarte, Antonio
   Isoniemi, Helena
   Laakkonen, Pirjo
   Christofori, Gerhard
   Yla-Herttuala, Seppo
   Shibuya, Masabumi
   Pytowski, Bronislaw
   Eichmann, Anne
   Betsholtz, Christer
   Alitalo, Kari
TI Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network
   formation
SO NATURE
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR-3; INHIBITS TUMOR-GROWTH; ENDOTHELIAL-CELLS;
   FACTOR-C; LYMPHATIC ENDOTHELIUM; LYMPHANGIOGENESIS; EXPRESSION; MOUSE;
   MICE; CANCER
AB Angiogenesis, the growth of new blood vessels from pre- existing vasculature, is a key process in several pathological conditions, including tumour growth and age- related macular degeneration(1). Vascular endothelial growth factors ( VEGFs) stimulate angiogenesis and lymphangiogenesis by activating VEGF receptor ( VEGFR) tyrosine kinases in endothelial cells(2). VEGFR- 3 ( also known as FLT- 4) is present in all endothelia during development, and in the adult it becomes restricted to the lymphatic endothelium(3). However, VEGFR- 3 is upregulated in the microvasculature of tumours and wounds(4,5). Here we demonstrate that VEGFR- 3 is highly expressed in angiogenic sprouts, and genetic targeting of VEGFR- 3 or blocking of VEGFR- 3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models. Stimulation of VEGFR- 3 augmented VEGF- induced angiogenesis and sustained angiogenesis even in the presence of VEGFR- 2 ( also known as KDR or FLK- 1) inhibitors, whereas antibodies against VEGFR- 3 and VEGFR- 2 in combination resulted in additive inhibition of angiogenesis and tumour growth. Furthermore, genetic or pharmacological disruption of the Notch signalling pathway led to widespread endothelial VEGFR- 3 expression and excessive sprouting, which was inhibited by blocking VEGFR- 3 signals. Our results implicate VEGFR- 3 as a regulator of vascular network formation. Targeting VEGFR- 3 may provide additional efficacy for anti- angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR- 2 inhibitors.
C1 [Tammela, Tuomas; Zarkada, Georgia; Murtomaki, Aino; Wirzenius, Maria; Waltari, Marika; Laakkonen, Pirjo; Alitalo, Kari] Univ Helsinki, Lab Mol Canc Biol, FIN-00014 Helsinki, Finland.
   [Tammela, Tuomas; Zarkada, Georgia; Murtomaki, Aino; Wirzenius, Maria; Waltari, Marika; Laakkonen, Pirjo; Alitalo, Kari] Univ Helsinki, Ludwig Inst Canc Res, Biomedicum Helsinki, FIN-00014 Helsinki, Finland.
   [Tammela, Tuomas; Zarkada, Georgia; Murtomaki, Aino; Wirzenius, Maria; Waltari, Marika; Laakkonen, Pirjo; Alitalo, Kari] Univ Helsinki, Haartman Inst, FIN-00014 Helsinki, Finland.
   [Wallgard, Elisabet; Hellstrom, Mats; Betsholtz, Christer] Karolinska Inst, Div Matrix Biol, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden.
   [Suchting, Steven; Freitas, Catarina; Eichmann, Anne] Coll France, INSERM, U833, F-75005 Paris, France.
   [Schomber, Tibor; Christofori, Gerhard] Univ Basel, Ctr Biomed, Dept Clin Biol Sci, CH-4058 Basel, Switzerland.
   [Peltonen, Reetta; Isoniemi, Helena] Univ Helsinki, Cent Hosp, Dept Transplantat & Hepat Surg, Helsinki 00029, Finland.
   [Duarte, Antonio] Univ Tecn Lisbon, Fac Vet Med, Interdisciplinary Ctr Res Anim Hlth CIISA, P-1300474 Lisbon, Portugal.
   [Yla-Herttuala, Seppo] Univ Kuopio, AI Virtanen Inst, FIN-70211 Kuopio, Finland.
   [Shibuya, Masabumi] Tokyo Med & Dent Univ, Dept Mol Oncol, Bunkyo Ku, Tokyo 1138519, Japan.
   [Pytowski, Bronislaw] ImClone Syst, New York, NY 10014 USA.
C3 University of Helsinki; Ludwig Institute for Cancer Research; University
   of Helsinki; University of Helsinki; Karolinska Institutet; Institut
   National de la Sante et de la Recherche Medicale (Inserm); UDICE-French
   Research Universities; PSL Research University Paris; College de France;
   University of Basel; University of Helsinki; Helsinki University Central
   Hospital; Universidade de Lisboa; University of Eastern Finland; Tokyo
   Medical & Dental University (TMDU); Eli Lilly
RP Alitalo, K (通讯作者)，Univ Helsinki, Lab Mol Canc Biol, POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland.
EM kari.alitalo@helsinki.fi
RI Alitalo, Kari K/J-5013-2014; Freitas, Catarina M/A-2555-2017; Duarte,
   Antonio/V-1178-2018
OI Alitalo, Kari K/0000-0002-7331-0902; Freitas, Catarina
   M/0000-0002-3393-5326; Duarte, Antonio/0000-0002-9255-3635;
   /0000-0003-3675-6961; Hellstrom, Mats/0000-0002-7088-9533;
   Yla-Herttuala, Seppo/0000-0001-7593-2708; Laakkonen,
   Pirjo/0000-0002-9620-095X
FU NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL075183] Funding Source:
   NIH RePORTER; NHLBI NIH HHS [5 R01 HL075183-02] Funding Source: Medline
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NR 50
TC 613
Z9 639
U1 0
U2 85
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 31
PY 2008
VL 454
IS 7204
BP 656
EP U68
DI 10.1038/nature07083
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 331QC
UT WOS:000258026500051
PM 18594512
DA 2022-11-30
ER

PT J
AU Thompson, JR
   Cappelleri, JC
   Getter, C
   Pleil, A
   Reichel, M
   Wolf, S
AF Thompson, John R.
   Cappelleri, Joseph C.
   Getter, Christine
   Pleil, Andreas
   Reichel, Martin
   Wolf, Sebastian
TI Enhanced interpretation of instrument scales using the Rasch model
SO DRUG INFORMATION JOURNAL
LA English
DT Article
DE instrument scales; item response theory; age-related macular
   degeneration; Rasch model; visual function questionnaire
ID LOW-VISION REHABILITATION; VISUAL FUNCTION QUESTIONNAIRE; FUNCTIONAL
   VISION; CATARACT PATIENTS; DISABILITY; LIFE; IMPAIRMENT; IMPACT; INDEX;
   VF-14
AB Objectives: To enhance the interpretability of instrument scales in general and the National Eye Institute Visual Function Questionnaire in particular. Methods: The Rasch model was applied to the German version of the 39-item National Eye Institute Visual Function Questionnaire in patients with age-related macular degeneration. Two important subscales, near vision and distance vision, were used in this work. The likelihood of performing a task with little or no difficulty was selected as an indicator of a patient's quality of life. Each possible subscale score was related to the likelihood of performing each task constituting the subscale with little or no difficulty. Results: The Rasch rating scale model was found to fit both subscales based on acceptable infit mean squares, a wide range of item difficulties, and monotonically increasing thresholds. Rasch category characteristic curves for each item in the subscale were back-transformed to the original scale of measurement and placed on a single graph. The graph provides a depiction of the relative difficulty of tasks, the probability of an individual performing a task without difficulty, and the expected mean performance of a group of individuals based on a subscale score. Results could be extended to access the impact of an intervention on the visual quality of life. Conclusions: This approach provides enhanced meaning to a subscale score while permitting the quantification of the improvement in the quality of life resulting from an intervention.
C1 Pfizer Global Res & Dev, New London, CT 06320 USA.
   Pfizer Global Res & Dev, Groton, CT USA.
   Pfizer Global Res & Dev, La Jolla, CA USA.
   Universitatsaugenklink Leipzig, Leipzig, Germany.
   Univ Bern, Inselspital, Klin & Poliklin Augenheilkunde, CH-3010 Bern, Switzerland.
C3 Pfizer; Pfizer; Pfizer; Leipzig University; University of Bern;
   University Hospital of Bern
RP Thompson, JR (通讯作者)，Pfizer Global Res & Dev, 50 Pequot Ave,MS MS 6025-A4168, New London, CT 06320 USA.
EM john.r.thompson@pfizer.com
RI Wolf, Sebastian/B-8782-2008
OI Wolf, Sebastian/0000-0002-7467-7028
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NR 27
TC 6
Z9 6
U1 0
U2 3
PU DRUG INFORMATION ASSOCIATION
PI HORSHAM
PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA
SN 0092-8615
J9 DRUG INF J
JI Drug Inf. J.
PY 2007
VL 41
IS 4
BP 541
EP 550
DI 10.1177/009286150704100413
PG 10
WC Health Care Sciences & Services; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services; Pharmacology & Pharmacy
GA 185MD
UT WOS:000247714200013
DA 2022-11-30
ER

PT J
AU Zareba, M
   Raciti, MW
   Henry, MM
   Sarna, T
   Burke, JM
AF Zareba, M
   Raciti, MW
   Henry, MM
   Sarna, T
   Burke, JM
TI Oxidative stress in ARPE-19 cultures: Do melanosomes confer
   cytoprotection?
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE RPE; melanin; melanosomes; oxidative stress in vitro; antioxidants; free
   radical
ID PIGMENT EPITHELIAL-CELLS; INDUCED DNA-DAMAGE; HUMAN RPE CELLS;
   HYDROGEN-PEROXIDE; BLUE-LIGHT; INDUCED APOPTOSIS; LIPID-PEROXIDATION;
   HYDROXYL RADICALS; SUBSTANTIA-NIGRA; GENE-EXPRESSION
AB The pigment melanin has antioxidant properties that could theoretically reduce oxidative damage to the retinal pigment epithelium (R-PE), perhaps protecting against retinal diseases with an oxidative stress component like age-related macular degeneration. To determine whether melanin confers cytoprotection on RPE cells, melanosomes or control particles were introduced by phagocytosis into the human cell line ARPE-19 and oxidative stress was induced chemically (H2O2 or tert-butyl hydroperoxide) or with visible light. Since the iron-binding capacity of melanin is important for its antioxidant function, experiments were performed to confirm that the melanosomes were not iron saturated. Cytotoxicity was assessed by measures of plasma or lysosomal membrane integrity, mitochondrial function, and cell-substrate reattachment. Oxidative stress protocols were critically evaluated to produce modest cytotoxicity, which might allow detection of a small cytoprotective effect as expected for melanosomes. Particle internalization alone had no effect on baseline metabolic activity or on major RPE antioxidants. Particles were tested in multiple oxidative stress experiments in which culture conditions known to affect stress-induced cytotoxicity, notably culture density, were varied. No testing condition or outcome measure revealed a consistent protective (or cytotoxic) effect of melanosomes, indicating that measures of lysosome stability or whole cell viability do not demonstrate an antioxidant role for RPE melanosomes. If the melanosome, all insoluble particle, performs a cytoprotective function within cells, its effects may be limited to the local environment of the organelle and undetectable by conventional methods. (c) 2005 Elsevier Inc. All rights reserved.
C1 Med Coll Wisconsin, Dept Ophthalmol, Inst Eye, Milwaukee, WI 53226 USA.
   Jagiellonian Univ, Fac Biotechnol, Dept Biophys, Krakow, Poland.
C3 Medical College of Wisconsin; Jagiellonian University
RP Burke, JM (通讯作者)，Med Coll Wisconsin, Dept Ophthalmol, Inst Eye, 925 N 87th St, Milwaukee, WI 53226 USA.
EM jburke@mcw.edu
FU NEI NIH HHS [P30 EY01931, R01 EY013722] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [R01EY013722, P30EY001931] Funding Source: NIH
   RePORTER
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   [No title captured]
NR 75
TC 57
Z9 58
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JAN 1
PY 2006
VL 40
IS 1
BP 87
EP 100
DI 10.1016/j.freeradbiomed.2005.08.015
PG 14
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 998AS
UT WOS:000234290900010
PM 16337882
DA 2022-11-30
ER

PT J
AU Halabi, R
   Watterston, C
   Hehr, CL
   Mori-Kreiner, R
   Childs, SJ
   McFarlane, S
AF Halabi, Rami
   Watterston, Charlene
   Hehr, Carrie Lynn
   Mori-Kreiner, Risa
   Childs, Sarah J.
   McFarlane, Sarah
TI Semaphorin 3fa Controls Ocular Vascularization From the Embryo Through
   to the Adult
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE angiogenesis; semaphorin; zebrafish; retinal pigment epithelium;
   vasculature
ID ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; ZEBRAFISH; VEGF; ANGIOGENESIS;
   VASCULATURE; EXPRESSION; NEOVASCULARIZATION; PATHOGENESIS; RETINOPATHY
AB PURPOSE. Pathological blood vessel growth in the eye is implicated in several diseases that result in vision loss, including age-related macular degeneration and diabetic retinopathy. The limits of current disease therapies have created the need to identify and characterize new antiangiogenic drugs. Here, we identify the secreted chemorepellent semaphorin-3fa (Sema3fa) as an endogenous anti-angiogenic in the eye.
   METHODS. We generated a CRISPR/Cas9 sema3fa zebrafish mutant line, sema3fa(ca304/304). We assessed the retinal and choroidal vasculature in both larval and adult wild-type and sema3fa mutant zebrafish.
   RESULTS. We find sema3fa mRNA is expressed by the ciliary marginal zone, neural retina, and retinal pigment epithelium of zebrafish larvae as choroidal vascularization emerges and the hyaloid/retinal vasculature is remodeled. The hyaloid vessels of sema3fa mutants develop appropriately but fail to remodel during the larval period, with adult mutants exhibiting a denser network of capillaries in the retinal periphery than seen in wild-type. The choroid vasculature is also defective in that it develops precociously, and aberrant, leaky sprouts are present in the normally avascular outer retina of both sema3fa(ca304/304) larvae and adult fish.
   CONCLUSIONS. Sema3fa is a key endogenous signal for maintaining an avascular retina and preventing pathologic vascularization. Furthermore, we provide a new experimentally accessible model for studying choroid neovascularization (CNV) resulting from primary changes in the retinal environment that lead to downstream vessel infiltration.
C1 [Halabi, Rami; Mori-Kreiner, Risa] Univ Calgary, Grad Program Neurosci, Calgary, AB, Canada.
   [Watterston, Charlene; Childs, Sarah J.] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada.
   [Halabi, Rami; Hehr, Carrie Lynn; Mori-Kreiner, Risa; McFarlane, Sarah] Univ Calgary, Dept Cell Biol & Anat, Calgary, AB, Canada.
   [Halabi, Rami; Hehr, Carrie Lynn; Mori-Kreiner, Risa; McFarlane, Sarah] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada.
   [Hehr, Carrie Lynn; Childs, Sarah J.; McFarlane, Sarah] Univ Calgary, Alberta Childrens Hosp Res Inst, Calgary, AB, Canada.
C3 University of Calgary; University of Calgary; University of Calgary;
   University of Calgary; University of Calgary
RP McFarlane, S (通讯作者)，Univ Calgary, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
EM smcfarla@ucalgary.ca
OI Watterston, Charlene/0000-0002-7603-1837
FU T. Chen Fong Hotchkiss Brain Institute studentship; Alberta
   Innovates-Health Solutions; Eyes High Studentship from the University of
   Calgary; Brightfocus Foundation; Fighting Blindness Canada; Canadian
   Institutes of Health Research
FX Supported by a T. Chen Fong Hotchkiss Brain Institute studentship, and
   by a studentship from Alberta Innovates-Health Solutions (R.H.), an Eyes
   High Studentship from the University of Calgary (C.W.), the Brightfocus
   Foundation (S.M.), Fighting Blindness Canada (S.M.), and project grants
   from the Canadian Institutes of Health Research (S.J.C., S.M.).
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NR 58
TC 2
Z9 2
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 FEB
PY 2021
VL 62
IS 2
AR 21
DI 10.1167/iovs.62.2.21
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QQ5MM
UT WOS:000624567800021
PM 33595613
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Lyzogubov, V
   Dasso, M
   Bora, N
   Bora, PS
AF Lyzogubov, Valeriy
   Dasso, Michael
   Bora, Nalini
   Bora, Puran. S.
TI Role of thalidomide, senicapoc, and sodium butyrate in choroidal
   neovascularization
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Age-related macular degeneration; Choroidal neovascularization;
   Thalidomide; Senicapoc; Sodium butyrate
ID COMPLEMENT REGULATORY PROTEIN; GARDOS CHANNEL BLOCKER; MACULAR
   DEGENERATION; MOUSE MODEL; GROWTH-FACTOR; IN-VITRO; CELLS; DRUG;
   PROLIFERATION; ANGIOGENESIS
AB Choroidal neovascularization (CNV) is the hallmark of wet age-related macular degeneration (AMD), a leading cause of irreversible blindness in the modern world. The objective for this study was to investigate the therapeutic potential of known antiangiogenic agents: thalidomide, senicapoc, and sodium butyrate. Dose-dependent effect of the agents on growth of ARPE-19 cells and human umbilical vein endothelial cells (HUVECs) was investigated with cell counting assays. Half-maximal inhibitory concentrations of thalidomide (765 mu M and 1520 mu M), senicapoc (50 mu M and 79 mu M), and sodium butyrate (933 mu M and 557 mu M) were determined for HUVECs and ARPE-19 cells, respectively. Immunofluorescence analysis showed decrease of VEGFA expression in both ARPE-19 cells and HUVECs after treatment only with thalidomide but not with senicapoc or sodium butyrate. Efficacy of the agents was studied in vivo with laser-induced CNV in C57BL/6 mice. Thalidomide (24 mu g), senicapoc (4 mu g), or sodium butyrate (100 mu g) was intravitreally injected the day after CNV induction. Thalidomide, senicapoc, and sodium butyrate inhibited CNV size by 56%, 24%, and 21% respectively on day 7 post-laser. Thalidomide also reduced cobalt chloride induced increase of VEGFA mRNA in ARPE-19 (-33%) and protein in culture medium (-20%). Our results suggest that thalidomide may have more therapeutic potential than senicapoc or sodium butyrate for treatment of CNV or wet AMD. (C) 2020 Elsevier Inc. All rights reserved.
C1 [Bora, Puran. S.] Univ Arkansas Med Sci, Dept Ophthalmol, Pat & Willard Walker Eye Res Ctr, Jones Eye Inst, 4301 West Markham St, Little Rock, AR 72205 USA.
   Univ Arkansas Med Sci, Coll Med, 4301 West Markham St, Little Rock, AR 72205 USA.
C3 University of Arkansas System; University of Arkansas Medical Sciences;
   University of Arkansas System; University of Arkansas Medical Sciences
RP Bora, PS (通讯作者)，Univ Arkansas Med Sci, Dept Ophthalmol, Pat & Willard Walker Eye Res Ctr, Jones Eye Inst, 4301 West Markham St, Little Rock, AR 72205 USA.
EM vvlyzogubov@uams.edu; MGDasso@uams.edu; nbora@uams.edu; pbora@uams.edu
OI Dasso, Michael/0000-0002-6946-2225
FU University of Arkansas for Medical Sciences Department of Ophthalmology
   Research Foundation, Pat & Willard Walker Eye Research Center, Jones Eye
   Institute
FX This work was supported in part by Phil Palade, PhD, and the University
   of Arkansas for Medical Sciences Department of Ophthalmology Research
   Foundation, Pat & Willard Walker Eye Research Center, Jones Eye
   Institute.
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NR 41
TC 2
Z9 2
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD SEP 17
PY 2020
VL 530
IS 2
BP 367
EP 373
DI 10.1016/j.bbrc.2020.07.140
PG 7
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA NI2LK
UT WOS:000565186800003
PM 32800337
DA 2022-11-30
ER

PT J
AU Leung, HH
   Galano, JM
   Crauste, C
   Durand, T
   Lee, JCY
AF Leung, Ho Hang
   Galano, Jean-Marie
   Crauste, Celine
   Durand, Thierry
   Lee, Jetty Chung-Yung
TI Combination of Lutein and Zeaxanthin, and DHA Regulated Polyunsaturated
   Fatty Acid Oxidation in H2O2-Stressed Retinal Cells
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE ARPE-19; Oxidative stress; Macular degeneration; Carotenoids; DHA;
   Glutathione
ID MACULAR DEGENERATION; GLUTATHIONE-PEROXIDASE; SUPEROXIDE-DISMUTASE;
   CAROTENOIDS; PROTEIN; CATALASE; ARPE-19; STRESS; ISOPROSTANES;
   TOCOPHEROLS
AB Photochemical and oxidative damages in retinal pigment epithelial (RPE) cells are key events in the pathogenesis of age-related macular degeneration. Polyunsaturated fatty acids (PUFA) and carotenoids are rich in retinal cells, and under oxidative stress leads to oxidation and release lipid mediators. We evaluated the impact of carotenoids (lutein, zeaxanthin) and docosahexaenoic acid (DHA) supplementation on RPE cells under oxidative stress. ARPE-19 cells were exposed to H2O2 after pre-treatment with lutein, zeaxanthin, DHA, lutein + zeaxanthin or lutein + zeaxanthin with DHA. The data showed H2O2 reduced cell viability and DHA content, while promoted catalase activity and certain oxidized PUFA products. Treatment with DHA enhanced omega-3 PUFA enzymatic oxidation namely, anti-inflammatory mediators such as hydroxy-DHA, resolvins and neuroprotection compared to control; the effects were not influenced by the carotenoids. Omega-6 PUFA oxidation, namely pro-inflammatory HETE (5-, 9-, 12 and 20-HETE), and isoprostanes (5- and 15-F-2t-IsoP and 4-F-3t-IsoP) were reduced by lutein + zeaxanthin while the addition of DHA did not further reduce these effects. We observed transcriptional regulation of 5-lipoxygenase by DHA and GPx1 and NEFEL2 by the carotenoids that potentially resulted in decreased HETEs and glutathione respectively. 4-HNE was not affected by the treatments but 4-HHE was reduced by lutein + zeaxanthin with and without DHA. To conclude, carotenoids and DHA appeared to regulate inflammatory lipid mediators while the carotenoids also showed benefits in reducing non-enzymatic oxidation of omega-6 PUFA.
C1 [Leung, Ho Hang; Lee, Jetty Chung-Yung] Univ Hong Kong, Sch Biol Sci, Pokfulam Rd, Hong Kong, Peoples R China.
   [Galano, Jean-Marie; Crauste, Celine; Durand, Thierry] Univ Montpellier, Inst Biomol Max Mousseron, ENSCM, UMR 5247,CNRS, Montpellier, France.
C3 University of Hong Kong; Centre National de la Recherche Scientifique
   (CNRS); CNRS - Institute of Chemistry (INC); Ecole nationale superieure
   de chimie de Montpellier; Universite de Montpellier
RP Lee, JCY (通讯作者)，Univ Hong Kong, Sch Biol Sci, Pokfulam Rd, Hong Kong, Peoples R China.
EM jettylee@hku.hk
RI Lee, Jetty Chung-Yung/E-1475-2011; Lee, Jetty Chung-Yung/S-1443-2019
OI Lee, Jetty Chung-Yung/0000-0002-8175-7069; Lee, Jetty
   Chung-Yung/0000-0002-8175-7069; Crauste, Celine/0000-0002-5714-8749
FU Health and Medical Research Fund [13142301]; Food and Health Bureau,
   Hong Kong
FX This work was supported by Health and Medical Research Fund (No.
   13142301), Food and Health Bureau, Hong Kong.
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NR 51
TC 8
Z9 8
U1 3
U2 11
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
EI 1573-6903
J9 NEUROCHEM RES
JI Neurochem. Res.
PD MAY
PY 2020
VL 45
IS 5
BP 1007
EP 1019
DI 10.1007/s11064-020-02994-4
EA FEB 2020
PG 13
WC Biochemistry & Molecular Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA LE0KF
UT WOS:000516346400001
PM 32088804
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Nakagami, Y
   Hatano, E
   Chayama, Y
   Inoue, T
AF Nakagami, Yasuhiro
   Hatano, Emiko
   Chayama, Yuichi
   Inoue, Tatsuya
TI An anti-PLVAP antibody suppresses laser-induced choroidal
   neovascularization in monkeys
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE PLVAP; VEGF; DME; Antibody; CNV
ID BLOOD-RETINAL BARRIER; VESICLE-ASSOCIATED PROTEIN; PAL-E; PERMEABILITY;
   EXPRESSION; DIAPHRAGMS; MOUSE; ENDOTHELIUM; AFLIBERCEPT; COMPONENT
AB Plasmalemma vesicle-associated protein (PLVAP, also called PV-1) is the only protein that forms endothelial diaphragms. PLVAP expression is very low in the normal blood-retinal barrier; however, pathological factors such as high glucose and vascular endothelial growth factor (VEGF) induce its expression, leading to the exacerbation of cellular permeability. Because the new blood vessels are fragile and leaky, PLVAP could possibly be considered a therapeutic target against retinovascular diseases. VEGF inhibitors are commonly used for the treatment of such diseases; however, there are several concerns associated with their use, especially in the case of chronic suppression of VEGF. In this study, we investigated the expressional level of PLVAP mRNA in VEGF-treated endothelial cells and the retinas of 2 animal models: streptozotocin-induced diabetic Brown Norway rats and Sprague-Dawley rats with oxygen-induced retinopathy. Among transcellular transport-related genes, the induction of PLVAP mRNA is the most apparent; the increase of PLVAP mRNA levels in the retina is evident during pathological progression. Furthermore, anti-PLVAP antibodies were generated, and their efficacy against laser-induced choroidal neovascularization was tested in cynomolgus monkeys. Although the leakage was exacerbated in the saline-injected group during the progression of neovascularization, the intravitreal injection of anti-PLVAP antibodies significantly ameliorated the exudation. These data imply that the PLVAP inhibition is a promising therapeutic approach against retinal diseases such as diabetic macular edema, retinopathy of prematurity, and we age-related macular degeneration.
C1 [Nakagami, Yasuhiro; Hatano, Emiko; Chayama, Yuichi; Inoue, Tatsuya] Daiichi Sankyo Co Ltd, Shinagawa R&D Ctr, Shinagawa Ku, 1-2-58 Hiromachi, Tokyo 1408710, Japan.
C3 Daiichi Sankyo Company Limited
RP Nakagami, Y (通讯作者)，Daiichi Sankyo Co Ltd, Shinagawa R&D Ctr, Shinagawa Ku, 1-2-58 Hiromachi, Tokyo 1408710, Japan.
EM nakagami.yasuhiro.y4@daiichisankyo.co.jp
OI Nakagami, Yasuhiro/0000-0003-3618-1715
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NR 43
TC 3
Z9 5
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
EI 1879-0712
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD JUL 5
PY 2019
VL 854
BP 240
EP 246
DI 10.1016/j.ejphar.2019.04.035
PG 7
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA HY7HQ
UT WOS:000468305200027
PM 31026444
DA 2022-11-30
ER

PT J
AU Chatziralli, I
   Theodossiadis, G
   Panagiotidis, D
   Pousoulidi, P
   Theodossiadis, P
AF Chatziralli, Irini
   Theodossiadis, George
   Panagiotidis, Dimitrios
   Pousoulidi, Paraskevi
   Theodossiadis, Panagiotis
TI Choriocapillaris' alterations in the presence of reticular pseudodrusen
   compared to drusen: study based on OCTA findings
SO INTERNATIONAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Drusen; Optical coherence tomography;
   Reticular pseudodrusen
ID OPTICAL COHERENCE TOMOGRAPHY; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; CHOROIDAL THICKNESS; VISUAL-ACUITY; PREVALENCE; EYES;
   RESTORATION; ANGIOGRAPHY; MORPHOLOGY
AB PurposeTo evaluate the qualitative changes of choriocapillaris in the presence of reticular pseudodrusen (RPD) and compare them with conventional small drusen due to dry age-related macular degeneration (AMD).ProceduresParticipants in this study were 59 patients with non-neovascular AMD, presenting either RPD (23 patients) or drusen (36 patients) of similar size. All patients underwent best-corrected visual acuity, slit-lamp examination, spectral domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography.ResultsThe morphology of RPD in SD-OCT was depicted either as conical or as amorphous in shape. Both types were found to affect the ellipsoid zone. The presence of RPD was associated with choriocapillaris' reduced blood flow signal (non-perfusion), while the same but less intense choriocapillaris' non-perfusion appearance was noticed in the presence of drusen of the same size. In 13% of patients with RPD, ghost-like vessels were observed in the non-perfusion area of choriocapillaris, while in none patients with drusen ghost vessels were present. In all 23 patients with RPD, the choriocapillaris non-perfusion was correspondent to the location of RPD. Additionally, in about 35% of them, choriocapillaris' impairment was also observed, covering areas outside RPD.ConclusionsMorphological impairment of choriocapillaris was more intense in patients with RPD than in those with conventional drusen of the same size. The existence of ghost vessels in the area of choriocapillaris' density defect suggested that choriocapillaris' alterations may occur in patients with RPD.
C1 [Chatziralli, Irini; Theodossiadis, George; Theodossiadis, Panagiotis] Univ Athens, Dept Ophthalmol 2, 1 Rimini St, Athens 12462, Greece.
   [Panagiotidis, Dimitrios; Pousoulidi, Paraskevi] Macula Ctr, Athens, Greece.
C3 National & Kapodistrian University of Athens
RP Chatziralli, I (通讯作者)，Univ Athens, Dept Ophthalmol 2, 1 Rimini St, Athens 12462, Greece.
EM eirchat@yahoo.gr
RI Chatziralli, Irini/AAG-4779-2020
OI Chatziralli, Irini/0000-0001-8523-1024
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NR 29
TC 15
Z9 15
U1 0
U2 3
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 OCT
PY 2018
VL 38
IS 5
BP 1887
EP 1893
DI 10.1007/s10792-017-0671-7
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GT5YK
UT WOS:000444586400010
PM 28779271
DA 2022-11-30
ER

PT J
AU Tamura, A
   Ohashi, M
   Nishida, K
   Yui, N
AF Tamura, Atsushi
   Ohashi, Moe
   Nishida, Kei
   Yui, Nobuhiko
TI Acid-Induced Intracellular Dissociation of beta-Cyclodextrin-Threaded
   Polyrotaxanes Directed toward Attenuating Phototoxicity of Bisretinoids
   through Promoting Excretion
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE polyrotaxane; cyclodextrin; triphenylmethyl group; retinoid;
   phototoxicity; age-related macular degeneration
ID RETINAL-PIGMENT EPITHELIUM; NIEMANN-PICK-DISEASE; MACULAR DEGENERATION;
   C DISEASE; LIPOFUSCIN FLUOROPHORE; INCLUSION COMPLEXES; A2E; CELLS;
   DRUG; ROTAXANES
AB In the retinal pigment epithelium of patients with age related macular degeneration (AMD), excess N-retinylidene-N-retinyle-thanolamine (A2E), a dimer of all-trans-retinal, accumulate to induce inflammatory cytokine secretion and phototoxic effects. Therefore, the reduction of intracellular A2E is a promising approach for the prevention and treatment of AMD. In this study, acid-labile beta-cyclodextrin (beta-CD)-threaded polyrotaxanes (PRXs) were synthesized and investigated their effects on the removal of A2E accumulated in retinal pigment epithelium cells (ARPE-19) in comparison to nonlabile PRXs and 2-hydroxypropyl beta-CD (HP-beta-CD) were examined. GC-MS and HPLC studies strongly suggest that the acid-labile PRXs dissociated into their constituent molecules in cells by lysosomal acidification and threaded beta-CDs were considered to be released from the PRXs. The released beta-CDs formed an inclusion complex with A2E, which promoted the excretion of A2E. Indeed, the acid-labile PRXs effectively reduced intracellular A2E level at approximately a 10-fold lower concentration than HP-beta-CD. Accompanied with A2E removal, the toxicity and phototoxicity of A2E were attenuated by treatment with acid-labile PRXs. Because the nonlabile PRX failed to reduce intracellular A2E level and attenuate phototoxicity, intracellular release of threaded beta-CDs from the acid-labile PRX might contribute to reducing intracellular A2E. We conclude that acid-labile PRXs are promising candidates for the treatment of macular diseases through the removal of toxic metabolites.
C1 [Tamura, Atsushi; Ohashi, Moe; Nishida, Kei; Yui, Nobuhiko] Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Dept Organ Biomat, Chiyoda Ku, 2-3-10 Kanda Surugadai, Tokyo 1010062, Japan.
C3 Tokyo Medical & Dental University (TMDU)
RP Yui, N (通讯作者)，Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Dept Organ Biomat, Chiyoda Ku, 2-3-10 Kanda Surugadai, Tokyo 1010062, Japan.
EM yui.org@tmd.ac.jp
RI Nishida, Kei/ABD-3842-2021
OI Nishida, Kei/0000-0001-6493-5436; Tamura, Atsushi/0000-0003-0235-7364
FU Japan Society for the Promotion of Science (JSPS) (JSPS KAKENHI)
   [JP16H05910]; Azuma Medical & Dental Research Grant; Ministry of
   Education, Culture, Sports, Science and Technology (MEXT)
FX This study was supported by the Grant-in-Aid for Young Scientists (A)
   from Japan Society for the Promotion of Science (JSPS) (JSPS KAKENHI
   Grant Number JP16H05910 to A.T.); Azuma Medical & Dental Research Grant
   (to A.T.); and Cooperative project among medicine, dentistry, and
   engineering for medical innovation "Construction of creative scientific
   research of the viable material via integration of biology and
   engineering" from the Ministry of Education, Culture, Sports, Science
   and Technology (MEXT).
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NR 60
TC 14
Z9 14
U1 0
U2 14
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD DEC
PY 2017
VL 14
IS 12
BP 4714
EP 4724
DI 10.1021/acs.molpharmaceut.7b00859
PG 11
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA FP1AO
UT WOS:000417342400056
PM 29120644
DA 2022-11-30
ER

PT J
AU Michelfelder, S
   Parsons, J
   Bohlender, LL
   Hoernstein, SNW
   Niederkruger, H
   Busch, A
   Krieghoff, N
   Koch, J
   Fode, B
   Schaaf, A
   Frischmuth, T
   Pohl, M
   Zipfe, PF
   Reski, R
   Decker, EL
   Haffner, K
AF Michelfelder, Stefan
   Parsons, Juliana
   Bohlender, Lennard L.
   Hoernstein, Sebastian N. W.
   Niederkrueger, Holger
   Busch, Andreas
   Krieghoff, Nicola
   Koch, Jonas
   Fode, Benjamin
   Schaaf, Andreas
   Frischmuth, Thomas
   Pohl, Martin
   Zipfe, Peter F.
   Reski, Ralf
   Decker, Eva L.
   Haeffner, Karsten
TI Moss-Produced, Glycosylation-Optimized Human Factor H for Therapeutic
   Application in Complement Disorders
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; DENSE DEPOSIT DISEASE; REGULATOR FACTOR-H;
   MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; PHYSCOMITRELLA-PATENS;
   FUNCTIONAL-ANALYSIS; STATISTICAL-MODEL; PLASMA THERAPY; C-TERMINUS;
   PROTEIN
AB Genetic defects in complement regulatory proteins can lead to severe renal diseases, including atypical hemolytic uremic syndrome and C3 glomerulopathies, and age-related macular degeneration. The majority of the mutations found in patients with these diseases affect the glycoprotein complement factor H, the main regulator of the alternative pathway of complement activation. Therapeutic options are limited, and novel treatments, specifically those targeting alternative pathway activation, are highly desirable. Substitution with biologically active factor H could potentially treat a variety of diseases that involve increased alternative pathway activation, but no therapeutic factor H is commercially available. We recently reported the expression of full-length recombinant factor H in moss (Physcomitrella patens). Here, we present the production of an improved moss-derived recombinant human factor H devoid of potentially immunogenic plant specific sugar residues on protein N-glycans, yielding approximately 1 mg purified moss derived human factor H per liter of initial P. patens culture after a multistep purification process. This glycosylation-optimized factor H showed full in vitro complement regulatory activity similar to that of plasma-derived factor H and efficiently blocked LPS-induced alternative pathway activation and hemolysis induced by sera from patients with atypical hemolytic uremic syndrome. Furthermore, injection of moss-derived factor H reduced C3 deposition and increased serum C3 levels in a murine model of C3 glomerulopathy. Thus, we consider moss-produced recombinant human factor H a promising pharmaceutical product for therapeutic intervention in patients suffering from complement dysregulation.
C1 [Michelfelder, Stefan; Pohl, Martin; Haeffner, Karsten] Univ Freiburg, Med Ctr, Fac Med, Dept Pediat & Adolescent Med, Freiburg, Germany.
   [Parsons, Juliana; Bohlender, Lennard L.; Hoernstein, Sebastian N. W.; Reski, Ralf; Decker, Eva L.] Univ Freiburg, Fac Biol, Plant Biotechnol, Schaenzlestr 1, D-79104 Freiburg, Germany.
   [Niederkrueger, Holger; Busch, Andreas; Krieghoff, Nicola; Koch, Jonas; Fode, Benjamin; Schaaf, Andreas; Frischmuth, Thomas] Greenovat Biotech GmbH, Freiburg, Germany.
   [Zipfe, Peter F.] Friedrich Schiller Univ, Leibniz Inst Nat Prod Res & Infect Biol, Jena, Germany.
   [Reski, Ralf] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, Freiburg, Germany.
   [Reski, Ralf] Univ Freiburg, FRIAS Freiburg Inst Adv Studies, Freiburg, Germany.
C3 University of Freiburg; University of Freiburg; Friedrich Schiller
   University of Jena; Hans Knoll Institute (HKI); University of Freiburg;
   University of Freiburg
RP Decker, EL (通讯作者)，Univ Freiburg, Fac Biol, Plant Biotechnol, Schaenzlestr 1, D-79104 Freiburg, Germany.; Haffner, K (通讯作者)，Univ Freiburg, Med Ctr, Dept Pediat & Adolescent Med, Mathildenstr 1, D-79111 Freiburg, Germany.
EM eva.decker@biologie.uni-freiburg.de;
   karsten.haeffner@uniklinik-freiburg.de
RI Parsons, Juliana/K-4652-2015
OI Michelfelder, Stefan/0000-0001-8678-1546; Reski,
   Ralf/0000-0002-5496-6711; Hoernstein, Sebastian/0000-0002-2095-689X
FU Glykobiologie/Glykomik of Baden-Wurttemberg Stiftung [P-BWS-Glyko/13];
   Excellence Initiative of the German Federal and States Governments
   [EXC294]; Collaborative Research Centre Immune-Mediated Glomerular
   Diseases -Deutsche Forschungsgemeinschaft [1192]; European Community
   [2012-305608]
FX This work was supported by contract research Glykobiologie/Glykomik of
   Baden-Wurttemberg Stiftung P-BWS-Glyko/13 and Excellence Initiative of
   the German Federal and States Governments grant EXC294 (to R.R.). P.F.Z.
   acknowledges support from Collaborative Research Centre 1192
   Immune-Mediated Glomerular Diseases funded by Deutsche
   Forschungsgemeinschaft Project B6 and has received funding from the
   European Community's Seventh Framework Programme under grant agreement
   no. 2012-305608, "European Consortium for High-Throughput Research in
   Rare Kidney Diseases (EURenOmics)". 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 73
TC 28
Z9 28
U1 0
U2 14
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAY
PY 2017
VL 28
IS 5
BP 1462
EP 1474
DI 10.1681/ASN.2015070745
PG 13
WC Urology & Nephrology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Urology & Nephrology
GA ET4BX
UT WOS:000400225100018
PM 27932477
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Jiang, C
   Qin, B
   Liu, GH
   Sun, XT
   Shi, HX
   Ding, SJ
   Liu, Y
   Zhu, MD
   Chen, X
   Zhao, C
AF Jiang, Chao
   Qin, Bing
   Liu, Guohua
   Sun, Xiantao
   Shi, Houxia
   Ding, Sijia
   Liu, Yuan
   Zhu, Meidong
   Chen, Xue
   Zhao, Chen
TI MicroRNA-184 promotes differentiation of the retinal pigment epithelium
   by targeting the AKT2/mTOR signaling pathway
SO ONCOTARGET
LA English
DT Article
DE miR-184; retinal pigment epithelium; differentiation; AKT2; mTOR
ID MACULAR DEGENERATION; THERAPEUTIC TARGET; STEM-CELLS; MIR-184;
   EXPRESSION; DEDIFFERENTIATION; KERATOCONUS; ACTIVATION; REPRESSION;
   SURVIVAL
AB Dedifferentiation of retinal pigment epithelium (RPE) cells is a crucial contributing factor to the pathology of retinal degenerative diseases, including age-related macular degeneration (AMD). Herein, we aim to reveal the roles of microRNAs (miRNAs) in RPE dedifferentiation and seek for potential therapeutic targets. Based on the microarray data, miR-184 was sorted out as the most up-regulated signature along with the differentiation from human induced pluripotent stem cells (hiPSC) to RPE cells, suggesting its potential promotive role in RPE differentiation. In vitro study indicated that miR-184 insufficiency suppressed RPE differentiation, typified by reduction of RPE markers, and promoted cell proliferation and migration. The role of miR-184 in maintaining regular RPE function was further proved in zebrafish studies. We also noticed that miR-184 expression was reduced in the macular RPE-choroid from a donor with RPE dysfunction compared to a healthy control. We next demonstrated that RAC-beta serine/threonine-protein kinase (AKT2) was a direct target for miR184. MiR-184 promoted RPE differentiation via suppression of AKT2/mammalian target of rapamycin (mTOR) signaling pathway. We also found that AKT2 was upregulated in macular RPE-choroid of the donor with RPE dysfunction and dry AMD patients. Taken together, our findings suggest that miR-184 insufficiency is involved in the pathogenesis of dry AMD. MiR-184 promotes RPE differentiation via inhibiting the AKT2/mTOR signaling pathway. MiR-184 based supplementary therapeutics and mTOR blocker, like rapamycin, are prospective options for AMD treatment.
C1 [Jiang, Chao; Qin, Bing; Shi, Houxia; Ding, Sijia; Chen, Xue; Zhao, Chen] Nanjing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Nanjing, Jiangsu, Peoples R China.
   [Jiang, Chao; Qin, Bing; Shi, Houxia; Ding, Sijia; Chen, Xue; Zhao, Chen] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China.
   [Qin, Bing] First Peoples Hosp Suqian, Dept Ophthalmol, Suqian, Peoples R China.
   [Liu, Guohua] Shandong Univ, Dept Ophthalmol, Qilu Hosp, Jinan, Shandong, Peoples R China.
   [Sun, Xiantao] Childrens Hosp Zhengzhou, Dept Ophthalmol, Zhengzhou, Peoples R China.
   [Liu, Yuan] Nanjing Med Univ, Dept Ophthalmol, Nanjing Hosp 1, Nanjing, Jiangsu, Peoples R China.
   [Zhu, Meidong] Univ Sydney, Discipline Clin Ophthalmol & Eye Hlth CO9, Save Sight Inst, Sydney, NSW, Australia.
   [Zhao, Chen] Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai, Peoples R China.
   [Zhao, Chen] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China.
C3 Nanjing Medical University; Nanjing Medical University; Shandong
   University; Nanjing Medical University; University of Sydney; Fudan
   University; Sun Yat Sen University
RP Chen, X; Zhao, C (通讯作者)，Nanjing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Nanjing, Jiangsu, Peoples R China.; Chen, X; Zhao, C (通讯作者)，Nanjing Med Univ, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China.; Zhao, C (通讯作者)，Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai, Peoples R China.; Zhao, C (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China.
EM drcx1990@163.com; dr_zhaochen@163.com
RI liu, yuan/L-9239-2018
OI liu, yuan/0000-0003-4887-907X
FU National Key Basic Research Program of China [2013CB967500]; National
   Natural Science Foundation of China [81525006]; Jiangsu Province's
   Innovation Team; Fundamental Research Funds of the State Key Laboratory
   of Ophthalmology; Priority Academic Program Development of Jiangsu
   Higher Education Institutions (PAPD)
FX This work was supported by National Key Basic Research Program of China
   (2013CB967500 to Chen Zhao); National Natural Science Foundation of
   China (81525006); Jiangsu Province's Innovation Team (to Chen Zhao); the
   Fundamental Research Funds of the State Key Laboratory of Ophthalmology
   (to Chen Zhao); and A Project Funded by the Priority Academic Program
   Development of Jiangsu Higher Education Institutions (PAPD).
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NR 43
TC 31
Z9 33
U1 3
U2 11
PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
EI 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD AUG 9
PY 2016
VL 7
IS 32
BP 52340
EP 52353
DI 10.18632/oncotarget.10566
PG 14
WC Oncology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Cell Biology
GA DY9CC
UT WOS:000385429100123
PM 27418134
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Hoffman, JD
   van Grinsven, MJJP
   Li, C
   Brantley, M
   McGrath, J
   Agarwal, A
   Scott, WK
   Schwartz, SG
   Kovach, J
   Pericak-Vance, M
   Sanchez, CI
   Haines, JL
AF Hoffman, Joshua D.
   van Grinsven, Mark J. J. P.
   Li, Chun
   Brantley, Milam, Jr.
   McGrath, Josephine
   Agarwal, Anita
   Scott, William K.
   Schwartz, Stephen G.
   Kovach, Jaclyn
   Pericak-Vance, Margaret
   Sanchez, Clara I.
   Haines, Jonathan L.
TI Genetic Association Analysis of Drusen Progression
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; drusen; genetic risk score analysis;
   image analysis
ID COMPLEMENT FACTOR-H; AGE-RELATED MACULOPATHY; OPTICAL COHERENCE
   TOMOGRAPHY; BODY-MASS INDEX; BEAVER DAM EYE; MACULAR DEGENERATION;
   GEOGRAPHIC ATROPHY; SUSCEPTIBILITY GENES; CUMULATIVE INCIDENCE;
   CIGARETTE-SMOKING
AB PURPOSE. Age-related macular degeneration is a common form of vision loss affecting older adults. The etiology of AMD is multifactorial and is influenced by environmental and genetic risk factors. In this study, we examine how 19 common risk variants contribute to drusen progression, a hallmark of AMD pathogenesis.
   METHODS. Exome chip data was made available through the International AMD Genomics Consortium (IAMDGC). Drusen quantification was carried out with color fundus photographs using an automated drusen detection and quantification algorithm. A genetic risk score (GRS) was calculated per subject by summing risk allele counts at 19 common genetic risk variants weighted by their respective effect sizes. Pathway analysis of drusen progression was carried out with the software package Pathway Analysis by Randomization Incorporating Structure.
   RESULTS. We observed significant correlation with drusen baseline area and the GRS in the age-related eye disease study (AREDS) dataset (q = 0.175, P = 0.006). Measures of association were not statistically significant between drusen progression and the GRS (P = 0.54). Pathway analysis revealed the cell adhesion molecules pathway as the most highly significant pathway associated with drusen progression (corrected P = 0.02).
   CONCLUSIONS. In this study, we explored the potential influence of known common AMD genetic risk factors on drusen progression. Our results from the GRS analysis showed association of increasing genetic burden (from 19 AMD associated loci) to baseline drusen load but not drusen progression in the AREDS dataset while pathway analysis suggests additional genetic contributors to AMD risk.
C1 [Hoffman, Joshua D.; McGrath, Josephine; Haines, Jonathan L.] Vanderbilt Univ, Ctr Human Genet Res, 221 Kirkland Hall, Nashville, TN 37235 USA.
   [van Grinsven, Mark J. J. P.; Sanchez, Clara I.] Radboud Univ Nijmegen, Med Ctr, Diagnost Image Anal Grp, NL-6525 ED Nijmegen, Netherlands.
   [Li, Chun] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
   [Brantley, Milam, Jr.; Agarwal, Anita] Vanderbilt Univ, Dept Ophthalmol & Visual Sci, 221 Kirkland Hall, Nashville, TN 37235 USA.
   [Scott, William K.; Pericak-Vance, Margaret] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA.
   [Schwartz, Stephen G.] Retina Ctr Naples, Bascom Palmer Eye Inst, Ophthalmol, Naples, FL USA.
   [Kovach, Jaclyn] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Haines, Jonathan L.] Case Western Reserve Univ, Inst Computat Biol, Cleveland, OH 44106 USA.
C3 Vanderbilt University; Radboud University Nijmegen; Case Western Reserve
   University; Vanderbilt University; University of Miami; Bascom Palmer
   Eye Institute; Bascom Palmer Eye Institute; University of Miami; Case
   Western Reserve University
RP Hoffman, JD (通讯作者)，Case Western Reserve Univ, Inst Computat Biol, Dept Epidemiol & Biostat, 2-529 Wolstein Res Bldg,2103 Cornell Rd, Cleveland, OH 44106 USA.
EM jlh213@case.edu
RI Gutierrez, Clara Isabel Sanchez/N-3580-2014; Haines,
   Jonathan/C-3374-2012; Li, Chun/R-1095-2019
OI Haines, Jonathan/0000-0002-4351-4728; Li, Chun/0000-0002-8819-2443;
   Scott, William/0000-0001-9336-6404
FU [A6019085];  [EY012118];  [AG019726];  [AG044089]; NATIONAL EYE
   INSTITUTE [R01EY012118, U10EY012118] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM080178] Funding
   Source: NIH RePORTER; NATIONAL INSTITUTE ON AGING [F31AG044089,
   R01AG019726] Funding Source: NIH RePORTER
FX Supported by Grants A6019085, EY012118, AG019726, and AG044089.
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NR 53
TC 12
Z9 12
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 APR
PY 2016
VL 57
IS 4
BP 2225
EP 2231
DI 10.1167/iovs.15-18571
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DL8XY
UT WOS:000375926700080
PM 27116550
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Kozhevnikova, OS
   Korbolina, EE
   Stefanova, NA
   Muraleva, NA
   Orlov, YL
   Kolosova, NG
AF Kozhevnikova, Oyuna S.
   Korbolina, Elena E.
   Stefanova, Natalia A.
   Muraleva, Natalia A.
   Orlov, Yuriy L.
   Kolosova, Nataliya G.
TI Association of AMD-like retinopathy development with an Alzheimer's
   disease metabolic pathway in OXYS rats
SO BIOGERONTOLOGY
LA English
DT Article
DE Aging; OXYS rats; Age-related macular degeneration; QTL; Beta-amyloid
   protein
ID GENOME-WIDE ASSOCIATION; MACULAR DEGENERATION; COMPLEMENT ACTIVATION;
   IDENTIFIES VARIANTS; BETA-PEPTIDE; AMYLOID-BETA; A-BETA; EXPRESSION;
   GENE; MICROARRAYS
AB The main cause of vision loss in older individuals is age-related macular degeneration (AMD)-a complex multifactorial disease, whose etiology and pathogenesis are not completely understood. This is due to the impossibility of investigating the early stages of AMD and paucity of biological models. The senescence-accelerated OXYS rats develop retinopathy with clinical and morphological manifestations similar to AMD. But the genetic determinants of its development are not known. Previously we identified quantitative trait loci (QTLs) associated with the development of cataract, retinopathy, and behavioral signs in OXYS rat. In this study, we used bioinformatic analysis to show the enrichment of QTL region with genes associated with neurodegeneration, including a pathway of Alzheimer's disease. For selected list of candidate genes we designed oligonucleotide DNA chips. Using them we found small but significant changes in expression of several genes in OXYS retina compared to disease-free Wistar rats. Among the genes with altered expression were Picalm and Apba2, known to be participants in the processing of the beta-amyloid (A beta). Measurement of A beta 1-42 in the retina showed that its level increases with age in rats, and at advanced stages of retinopathy in OXYS rats, its expression becomes significantly higher than that of disease-free Wistar rats. Based on functional annotation of QTL, microarray, and ELISA results we suggest that accumulation of A beta may have a role in the pathogenesis of retinopathy in OXYS rats.
C1 [Kozhevnikova, Oyuna S.; Korbolina, Elena E.; Stefanova, Natalia A.; Muraleva, Natalia A.; Orlov, Yuriy L.; Kolosova, Nataliya G.] SB RAS, Inst Cytol & Genet, Novosibirsk, Russia.
C3 Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB RAS
RP Kolosova, NG (通讯作者)，SB RAS, Inst Cytol & Genet, Novosibirsk, Russia.
EM kolosova@bionet.nsc.ru
RI Orlov, Yuriy L/F-1520-2013; Kolosova, Nataliya G/P-3178-2015; Muraleva,
   Natalia/S-2392-2018; Kolosova, Nataliya G/AAR-7409-2020; Stefanova,
   Natalia/V-1530-2018; Kozhevnikova, Oyuna S./H-3588-2016
OI Orlov, Yuriy L/0000-0003-0587-1609; Kolosova, Nataliya
   G/0000-0003-2398-8544; Muraleva, Natalia/0000-0002-0665-1723; Kolosova,
   Nataliya G/0000-0003-2398-8544; Kozhevnikova, Oyuna
   S./0000-0001-6475-4061; Stefanova, natalia/0000-0001-5127-5993
FU Russian Foundation for Basic Research [11-04-00666-a, 12-04-00091-a,
   12-04-31975]; Government of the Russian Federation [14.B25.31.0033, 220]
FX Microscopy was performed in the Microscopy Centre of Institute Cytology
   and Genetics SB RAS. We thank A. Shvalov and S.I. Baiborodin for
   technical assistance and Dr. E. Rogaev for helpful discussion. This
   study was supported by Russian Foundation for Basic Research Grants
   (project 11-04-00666-a, 12-04-00091-a and 12-04-31975) and partially by
   Project No. 14.B25.31.0033, Resolution No. 220 of the Government of the
   Russian Federation of April 9, 2010.
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NR 43
TC 27
Z9 31
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1389-5729
EI 1573-6768
J9 BIOGERONTOLOGY
JI Biogerontology
PD DEC
PY 2013
VL 14
IS 6
SI SI
BP 753
EP 762
DI 10.1007/s10522-013-9439-2
PG 10
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA 266XC
UT WOS:000328056300020
PM 23959258
DA 2022-11-30
ER

PT J
AU Palamoor, M
   Jablonski, MM
AF Palamoor, Mallika
   Jablonski, Monica M.
TI Synthesis, characterization and in vitro studies of celecoxib-loaded
   poly(ortho ester) nanoparticles targeted for intraocular drug delivery
SO COLLOIDS AND SURFACES B-BIOINTERFACES
LA English
DT Article
DE Poly(ortho ester); Celecoxib; Nanoparticles; Solvent diffusion; Nile
   red; Cytotoxicity
ID CONTROLLED-RELEASE; BIOAVAILABILITY; SYSTEMS; PHASE; CELLS; ACID; FOOD
AB The present investigation is aimed at improving the ocular bioavailability of a poorly water soluble drug, celecoxib, to offer new options in the treatment of chronic eye diseases, such as age-related macular degeneration and diabetic retinopathy. To do so, we developed a novel formulation of drug-loaded poly(ortho ester) nanoparticles (NPs). We characterized the NPs in terms of size, morphology, controlledrelease, degradation and cytocompatibity. Stable and transparent NP emulsions were prepared following a double emulsion solvent diffusion method employing poloxamer 188 as a stabilizer. Physical properties showed a narrow range size distribution of 151-164 nm with spherical morphology, negative zeta potentials and remarkably high celecoxib encapsulation efficiency (98%) and loading (64%) of poly(ortho ester) NPs. Drug release followed a zero-order release by a surface erosion-controlled mechanism without any burst effect. Degradation of poly(ortho ester) NPs was observed by measuring the concentration of initial degradation product such as, lactic acid. MU studies revealed minimal toxicity of NPs (up to 1 mg/ml) toward HER 293 cells. Poly(ortho ester) NPs were not internalized by either Muller or HEK 293 cells, which is highly desirable for a drug carrier to deliver the drugs for prolonged periods to the back of eye. These features have the potential to decrease the number of intraocular injections required to treat chronic eye diseases. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Palamoor, Mallika; Jablonski, Monica M.] Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, Memphis, TN 38163 USA.
   [Jablonski, Monica M.] Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, 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
RP Jablonski, MM (通讯作者)，Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, 930 Madison Ave,Suite 731, Memphis, TN 38163 USA.
EM mpalamoo@uthsc.edu; mjablonski@uthsc.edu
FU NEI [P30EY013080]; March of Dimes Grant [6-FY09-281]; Fight For Sight
   Grant [FFS-PD-10-009]; Knights Templar Eye Foundation, Flower Mound, TX;
   Research to Prevent Blindness, New York, NY
FX We express appreciation to Dr. Liyuan Li for providing cell cultures.
   This study was supported by an NEI Core Grant P30EY013080, March of
   Dimes Grant 6-FY09-281; Fight For Sight Grant FFS-PD-10-009; Knights
   Templar Eye Foundation, Flower Mound, TX; and an unrestricted grant from
   Research to Prevent Blindness, New York, NY.
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NR 43
TC 17
Z9 18
U1 0
U2 51
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0927-7765
EI 1873-4367
J9 COLLOID SURFACE B
JI Colloid Surf. B-Biointerfaces
PD DEC 1
PY 2013
VL 112
BP 474
EP 482
DI 10.1016/j.colsurfb.2013.07.039
PG 9
WC Biophysics; Chemistry, Physical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biophysics; Chemistry; Materials Science
GA 274FV
UT WOS:000328593100068
PM 24103464
DA 2022-11-30
ER

PT J
AU Suen, WLL
   Chau, Y
AF Suen, Wai-Leung Langston
   Chau, Ying
TI Specific uptake of folate-decorated triamcinolone-encapsulating
   nanoparticles by retinal pigment epithelium cells enhances and prolongs
   antiangiogenic activity
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Corticosteroid; Ocular delivery; Choroidal neovascularization; VEGF;
   Receptor-mediated endocytosis
ID ENDOTHELIAL GROWTH-FACTOR; BLOCK-COPOLYMER MICELLES; MACULAR
   DEGENERATION; DRUG-DELIVERY; INTRAVITREAL INJECTION; GENE DELIVERY;
   ACETONIDE; THERAPY; VEGF; PEDF
AB We are proposing folate-decorated polymeric nanoparticles as carriers of poorly soluble drug molecules for intracellular and prolonged delivery to retinal pigment epithelium (RPE) cells. RPE is a monolayer of epithelial cells that forms the outer blood-retinal barrier in the posterior segment of the eye, and is also implicated in the pathology of, such as neovascularization in age-related macular degeneration (AMD). In this study, folate-functionalized poly(ethylene glycol)-b-polycaprolactone (folate-PEG-b-PCL) were synthesized for assembling into nanoparticles of similar to 130 nm. These nanoparticles were internalized into ARPE-19 (human RPE cell line) via receptor-mediated endocytosis, and the cellular uptake was significantly higher than particles without folate modification. Triamcinolone acetonide (TA) was efficiently encapsulated (> 97%) into the folate-decorated nanoparticles and was slowly released over a period of 4 weeks at pH 5.5 and 8 weeks at pH 7.4. The enhanced uptake and controlled release resulted in prolonged anti-angiogenic gene expression of RPE cells. In cell culture, the down-regulation of vascular endothelial growth factor (VEGF) and up-regulation of pigment epithelium derived factor (PEDF) lasted for at least 3 weeks. Unlike benzyl alcohol, the surfactant found in commercial formulation, folate-modified nanoparticles were non-toxic. Furthermore, TA became less cytotoxic by being encapsulated in the nanoparticles. Our findings suggest that folate-PEG-PCL nanoparticles are promising drug carriers for RPE targeting. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Suen, Wai-Leung Langston; Chau, Ying] Hong Kong Univ Sci & Technol, Dept Chem & Biomol Engn, Kowloon, Hong Kong, Peoples R China.
   [Chau, Ying] Hong Kong Univ Sci & Technol, Div Biomed Engn, Kowloon, Hong Kong, Peoples R China.
C3 Hong Kong University of Science & Technology; Hong Kong University of
   Science & Technology
RP Chau, Y (通讯作者)，Hong Kong Univ Sci & Technol, Dept Chem & Biomol Engn, Kowloon, Hong Kong, Peoples R China.
EM keychau@ust.hk
OI Chau, Ying/0000-0003-1759-934X
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NR 43
TC 51
Z9 53
U1 3
U2 86
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
J9 J CONTROL RELEASE
JI J. Control. Release
PD APR 10
PY 2013
VL 167
IS 1
BP 21
EP 28
DI 10.1016/j.jconrel.2013.01.004
PG 8
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Pharmacology & Pharmacy
GA 113OT
UT WOS:000316678100003
PM 23313961
DA 2022-11-30
ER

PT J
AU Rezaie, T
   McKercher, SR
   Kosaka, K
   Seki, M
   Wheeler, L
   Viswanath, V
   Chun, T
   Joshi, R
   Valencia, M
   Sasaki, S
   Tozawa, T
   Satoh, T
   Lipton, SA
AF Rezaie, Tayebeh
   McKercher, Scott R.
   Kosaka, Kunio
   Seki, Masaaki
   Wheeler, Larry
   Viswanath, Veena
   Chun, Teresa
   Joshi, Rabina
   Valencia, Marcos
   Sasaki, Shunsuke
   Tozawa, Terumasa
   Satoh, Takumi
   Lipton, Stuart A.
TI Protective Effect of Carnosic Acid, a Pro-Electrophilic Compound, in
   Models of Oxidative Stress and Light-Induced Retinal Degeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ANTIOXIDANT-RESPONSIVE ELEMENT; MACULAR DEGENERATION; CELL-DEATH;
   SULFINIC ACID; MOLECULAR-MECHANISMS; IN-VIVO; APOPTOSIS; PEROXIREDOXIN;
   SULFIREDOXIN; EXPRESSION
AB PURPOSE. The herb rosemary has been reported to have antioxidant and anti-inflammatory activity. We have previously shown that carnosic acid (CA), present in rosemary extract, crosses the blood-brain barrier to exert neuroprotective effects by upregulating endogenous antioxidant enzymes via the Nrf2 transcriptional pathway. Here we investigated the antioxidant and neuroprotective activity of CA in retinal cell lines exposed to oxidative stress and in a rat model of light-induced retinal degeneration (LIRD).
   METHODS. Retina-derived cell lines ARPE-19 and 661W treated with hydrogen peroxide were used as in vitro models for testing the protective activity of CA. For in vivo testing, dark-adapted rats were given intraperitoneal injections of CA prior to exposure to white light to assess protection of the photoreceptor cells. Retinal damage was assessed by measuring outer nuclear layer thickness and by electroretinogram (ERG).
   RESULTS. In vitro, CA significantly protected retina-derived cell lines (ARPE-19 and 661W) against H2O2-induced toxicity. CA induced antioxidant phase 2 enzymes and reduced formation of hyperoxidized peroxiredoxin (Prx)2. Similarly, we found that CA protected retinas in vivo from LIRD, producing significant improvement in outer nuclear layer thickness and ERG activity.
   CONCLUSIONS. These findings suggest that CA may potentially have clinical application to diseases affecting the outer retina, including age-related macular degeneration and retinitis pigmentosa, in which oxidative stress is thought to contribute to disease progression. (Invest Ophthalmol Vis Sci. 2012; 53:7847-7854) DOI:10.1167/iovs.12-10793
C1 [Rezaie, Tayebeh; McKercher, Scott R.; Seki, Masaaki; Joshi, Rabina; Valencia, Marcos; Satoh, Takumi; Lipton, Stuart A.] Sanford Burnham Med Res Inst, Del E Web Ctr Neurosci Aging & Stem Cell Res, La Jolla, CA USA.
   [Kosaka, Kunio] Nagase & Co Ltd, Ctr Res & Dev, Kobe, Hyogo, Japan.
   [Wheeler, Larry; Viswanath, Veena; Chun, Teresa] Allergan Pharmaceut Inc, Dept Biol Sci, Irvine, CA USA.
   [Sasaki, Shunsuke; Tozawa, Terumasa; Satoh, Takumi] Iwate Univ, Fac Engn, Dept Welf Engn, Morioka, Iwate 020, Japan.
C3 Sanford Burnham Prebys Medical Discovery Institute; Nagase & Co., Ltd.;
   AbbVie; Allergan; Iwate University
RP Lipton, SA (通讯作者)，10901 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM slipton@sanfordburnham.org
OI Lipton, Stuart/0000-0002-3490-1259
FU National Institutes of Health [R01EY05477, P01 HD29587, P01 ES016738,
   P30 NS076411]; Allergan, Inc., Irvine, California; EUNICE KENNEDY
   SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
   [P01HD029587] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R01EY005477] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   ENVIRONMENTAL HEALTH SCIENCES [P01ES016738] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
   [P30NS076411] Funding Source: NIH RePORTER
FX Supported in part by National Institutes of Health Grants R01EY05477,
   P01 HD29587, P01 ES016738, and P30 NS076411, and by Allergan, Inc.,
   Irvine, California.
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NR 50
TC 53
Z9 66
U1 1
U2 19
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 2012
VL 53
IS 12
BP 7847
EP 7854
DI 10.1167/iovs.12-10793
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 064EE
UT WOS:000313053500059
PM 23081978
OA Green Published
DA 2022-11-30
ER

PT J
AU Raoul, W
   Poupel, L
   Tregouet, DA
   Lavalette, S
   Camelo, S
   Keller, N
   Krumeich, S
   Calippe, B
   Guillonneau, X
   Behar-Cohen, F
   Cohen, SY
   Baatz, H
   Combadiere, C
   Thery, C
   Sennlaub, F
AF Raoul, William
   Poupel, Lucie
   Tregouet, David-Alexandre
   Lavalette, Sophie
   Camelo, Serge
   Keller, Nicole
   Krumeich, Sophie
   Calippe, Bertrand
   Guillonneau, Xavier
   Behar-Cohen, Francine
   Cohen, Salomon-Yves
   Baatz, Holger
   Combadiere, Christophe
   Thery, Clotilde
   Sennlaub, Florian
TI MFGE8 Does Not Influence Chorio-Retinal Homeostasis or Choroidal
   Neovascularization in vivo
SO PLOS ONE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; ROD OUTER SEGMENTS; MACULAR DEGENERATION;
   PIGMENT EPITHELIUM; APOPTOTIC CELLS; ALPHA-V-BETA-5 INTEGRIN; MFG-E8;
   PHAGOCYTOSIS; PREVALENCE; RECEPTOR
AB Purpose: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or "wet" Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice.
   Methods: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with "wet" AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8(+/-) mice expressing beta-galactosidase. Aged Mfge8(+/-) and Mfge8(-/-) mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV.
   Results: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8(-/-) mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8(-/-) mice as compared to controls.
   Conclusions: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8(-/-) mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD.
C1 [Raoul, William; Lavalette, Sophie; Calippe, Bertrand; Guillonneau, Xavier; Sennlaub, Florian] INSERM, U968, Paris, France.
   [Raoul, William; Lavalette, Sophie; Calippe, Bertrand; Guillonneau, Xavier; Sennlaub, Florian] Univ Paris 06, Inst Vis, Paris, France.
   [Behar-Cohen, Francine; Sennlaub, Florian] Hop Hotel Dieu, AP HP, Serv Ophtalmol, Paris, France.
   [Raoul, William; Lavalette, Sophie; Calippe, Bertrand; Guillonneau, Xavier; Sennlaub, Florian] Ctr Natl Rech Sci, Paris, France.
   [Poupel, Lucie; Combadiere, Christophe] INSERM, Lab Immun & Infect, UMR S945, Paris, France.
   [Poupel, Lucie; Combadiere, Christophe] Univ Paris 06, Lab Immun & Infect, Paris, France.
   [Combadiere, Christophe] Grp Hosp Pitie Salpetriere, AP HP, Serv Immunol, F-75634 Paris, France.
   [Camelo, Serge; Keller, Nicole; Behar-Cohen, Francine] Ctr Rech Cordeliers, INSERM, UMR S 872, Paris, France.
   [Camelo, Serge; Keller, Nicole; Behar-Cohen, Francine] Univ Paris 05, Paris, France.
   [Krumeich, Sophie; Thery, Clotilde] INSERM, U932, Paris, France.
   [Krumeich, Sophie; Thery, Clotilde] Ctr Rech, Inst Curie, Paris, France.
   [Baatz, Holger] Goethe Univ Frankfurt, Augenzentrum Recklinghausen, Augenarztl Gemeinschaftspraxis, Frankfurt, Germany.
   [Baatz, Holger] Goethe Univ Frankfurt, Zentrum Augenheilkunde, Frankfurt, Germany.
   [Cohen, Salomon-Yves] Ctr Angiog & Laser, Paris, France.
   [Tregouet, David-Alexandre] INSERM, Fac Med La Pitie Salpetriere, UMR S 937, Paris, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Sorbonne Universite; Assistance
   Publique Hopitaux Paris (APHP); Hopital Universitaire Hotel-Dieu - APHP;
   UDICE-French Research Universities; Universite Paris Cite; Centre
   National de la Recherche Scientifique (CNRS); Institut National de la
   Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite; Assistance Publique Hopitaux Paris
   (APHP); Hopital Universitaire Pitie-Salpetriere - APHP; UDICE-French
   Research Universities; Sorbonne Universite; Institut National de la
   Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite; Universite Paris Cite; UDICE-French
   Research Universities; Universite Paris Cite; UDICE-French Research
   Universities; PSL Research University Paris; UNICANCER; Institut Curie;
   Institut National de la Sante et de la Recherche Medicale (Inserm);
   Universite Paris Cite; UDICE-French Research Universities; PSL Research
   University Paris; UNICANCER; Institut Curie; Goethe University
   Frankfurt; Goethe University Frankfurt; Institut National de la Sante et
   de la Recherche Medicale (Inserm); UDICE-French Research Universities;
   Sorbonne Universite
RP Raoul, W (通讯作者)，INSERM, U968, Paris, France.
EM william.raoul@inserm.fr; florian.sennlaub@inserm.fr
RI Tregouet, David-Alexandre/E-3961-2016; Raoul, William/H-2118-2018;
   guillonneau, xavier/AAF-9495-2021; Sennlaub, Florian/F-2756-2017;
   Combadiere, Christophe/I-5639-2013; Guillonneau, xavier/E-3995-2017;
   thery, clotilde/F-6373-2013; Trégouët, David-Alexandre/P-9210-2019
OI Raoul, William/0000-0002-5040-3372; guillonneau,
   xavier/0000-0001-7379-3935; Sennlaub, Florian/0000-0003-4412-1341;
   Combadiere, Christophe/0000-0002-1755-4531; Guillonneau,
   xavier/0000-0001-7379-3935; thery, clotilde/0000-0001-8294-6884;
   Trégouët, David-Alexandre/0000-0001-9084-7800; Camelo,
   Serge/0000-0001-8733-8503; Poupel, Lucie/0000-0001-7015-8450
FU INSERM; Agence Nationale pour la Recherche (ANR) "blanc" [AO5120DD]; ANR
   "Maladies Neurologiques et Maladies Psychiatriques" [R08098DS]; ANR
   "Genopat" [R09099DS]; European Grant "Innochem" [LSHB-CT-2005-518167];
   ERC [ERC-2007 St.G. 210345]; Fondation de France; Assistance
   Publique-Hopitaux de Paris
FX This work was supported by grants from INSERM, Agence Nationale pour la
   Recherche (ANR) "blanc" (AO5120DD), ANR "Maladies Neurologiques et
   Maladies Psychiatriques" (R08098DS), ANR "Genopat" (R09099DS), European
   Grant "Innochem" (LSHB-CT-2005-518167), ERC starting Grant (ERC-2007
   St.G. 210345), and a grant from Fondation de France to C. T. F. S. a is
   recipient of ERC starting grant. C. C. and F. S. are recipients of a
   contract "Interface" from Assistance Publique-Hopitaux de Paris. 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 2
Z9 3
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 MAR 15
PY 2012
VL 7
IS 3
AR e33244
DI 10.1371/journal.pone.0033244
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 932RU
UT WOS:000303309000015
PM 22438901
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Han, DP
   McAllister, JT
   Weinberg, DV
   Kim, JE
   Wirostko, WJ
AF Han, D. P.
   McAllister, J. T.
   Weinberg, D. V.
   Kim, J. E.
   Wirostko, W. J.
TI Combined intravitreal anti-VEGF and verteporfin photodynamic therapy for
   juxtafoveal and extrafoveal choroidal neovascularization as an
   alternative to laser photocoagulation
SO EYE
LA English
DT Article
DE extrafoveal choroidal neovascularization; anti-VEGF therapy;
   photodynamic therapy; age-related macular degeneration; ocular
   histoplasmosis; degenerative myopia
ID MACULAR DEGENERATION; RANIBIZUMAB
AB Purpose To evaluate anti-VEGF and photodynamic therapy (PDT) for juxtafoveal and extrafoveal choroidal neovascularization (CNV) due to age-related macular degeneration (ARMD), ocular histoplasmosis syndrome (OHS), and degenerative myopia.
   Methods A total of 10 eyes with juxtafoveal or extrafoveal choroidal neovascularization underwent intravitreal anti-VEGF therapy combined with verteporfin PDT (689 nm). Most treatments consisted of PDT every 12 weeks and either ranibizumab 0.5mg every 4 weeks or bevacizumab 1.25mg every 6 weeks, initiated concurrently. Retreatment criteria were persistent exudative signs on optical coherence tomography or fluorescein angiography.
   Results Presenting visual acuity (VA) ranged from 20/20 to 20/60 (mean log MAR +/- SD, 0.338 +/- 0.16 (20/44 equivalent)). After a mean follow-up of 17.5 months, it ranged from 20/15 to 20/40 (mean log MAR +/- SD, 0.150 +/- 0.14 (20/28 equivalent); P = 0.027, paired t-test). Six eyes improved by >= 2 lines and four remained within 2 lines of initial VA. Non-ARMD eyes required much fewer treatments than ARMD eyes. All five non-ARMD eyes and three of five ARMD eyes showed no CNV activity at least 5 months after last treatment.
   Conclusions Anti-VEGF therapy and PDT can preserve good visual function and may be suited to some cases of nonfoveal CNV. ARMD eyes require longer courses of treatment than non-ARMD eyes. Eye (2010) 24, 713-716; doi: 10.1038/eye.2009.122; published online 5 June 2009
C1 [Han, D. P.] Med Coll Wisconsin, Dept Ophthalmol, Froedtert & MCW Eye Inst, Milwaukee, WI 53226 USA.
C3 Medical College of Wisconsin
RP Han, DP (通讯作者)，Med Coll Wisconsin, Dept Ophthalmol, Froedtert & MCW Eye Inst, 925 N 87th St, Milwaukee, WI 53226 USA.
EM dhan@mcw.edu
OI Weinberg, David/0000-0002-1974-9252
FU Research to Prevent Blindness Inc., New York, NY, USA; Allergan Inc.;
   Genentech Inc.; Novartis Inc
FX This study was supported in part by an unrestricted grant from Research
   to Prevent Blindness Inc., New York, NY, USA.; The institution with
   which the authors DP Han, WJ Wirostko, DV Weinberg, and JE Kim are
   affiliated (Medical College of Wisconsin, Milwaukee, WI, USA) receives
   research funds to conduct clinical trials from the following entities:
   Allergan Inc., Genentech Inc., and Novartis Inc.
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NR 8
TC 13
Z9 13
U1 0
U2 3
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 APR
PY 2010
VL 24
IS 4
BP 713
EP 716
DI 10.1038/eye.2009.122
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 583SY
UT WOS:000276701300032
PM 19498454
OA Bronze
DA 2022-11-30
ER

PT J
AU Isas, JM
   Luibl, V
   Johnson, LV
   Kayed, R
   Wetzel, R
   Glabe, CG
   Langen, R
   Chen, J
AF Isas, J. Mario
   Luibl, Volker
   Johnson, Lincoln V.
   Kayed, Rakez
   Wetzel, Ronald
   Glabe, Charles G.
   Langen, Ralf
   Chen, Jeannie
TI Soluble and Mature Amyloid Fibrils in Drusen Deposits
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MACULAR DEGENERATION; COMPLEMENT ACTIVATION; APOLIPOPROTEIN-E; MOUSE
   MODEL; BETA; ALZHEIMERS; OLIGOMERS; COMMON; PATHOGENESIS; ANTIBODIES
AB PURPOSE. Drusen are a hallmark of eyes affected by age-related macular degeneration. In previous study, a conformational-specific antibody showed drusen to contain nonfibrillar amyloid structures. The current study was undertaken to assess the presence of additional amyloid structures in drusen.
   METHODS. Sections from human donor eyes were reacted with M204, a monoclonal antibody that recognizes nonfibrillar oligomers; OC, a polyclonal antibody that recognizes amyloid fibrils of various molecular weights; and WO1 and WO2, monoclonal antibodies that are specifically reactive to mature amyloid fibrils. Electron microscopy was used as an independent means of investigating the presence of amyloid fibrils in drusen.
   RESULTS. The presence of nonfibrillar oligomers was verified using the M204 antibody. OC and WO antibodies stained a wide spectrum of vesicular structures. OC reactivity showed extensive overlap with A beta immunoreactivity, whereas a partial overlap was seen between A beta reactivity and that of the WO antibodies. The presence of amyloid fibrils was also visualized by electron microscopy.
   CONCLUSIONS. These data reveal the presence of a wide spectrum of amyloid structures in drusen. The results are significant, given that specific conformational forms of amyloid are known to be pathogenic in a variety of neurodegenerative diseases. Deposition of these structures may lead to local toxicity of the retinal pigmented epithelium or induction of local inflammatory events that contribute to drusen biogenesis and the pathogenesis of AMD. (Invest Ophthalmol Vis Sci. 2010;51:1304-1310) DOI:10.1167/iovs.09-4207
C1 [Luibl, Volker; Chen, Jeannie] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA.
   [Luibl, Volker; Chen, Jeannie] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Ophthalmol, Los Angeles, CA 90033 USA.
   [Isas, J. Mario; Langen, Ralf] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA.
   [Johnson, Lincoln V.] Univ Calif Santa Barbara, Neurosci Res Inst, Ctr Study Macular Degenerat, Santa Barbara, CA 93106 USA.
   [Kayed, Rakez] Univ Texas Med Branch, Dept Neurol, Sch Med, Galveston, TX USA.
   [Wetzel, Ronald] Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Dis, Dept Biol Struct, Pittsburgh, PA USA.
   [Glabe, Charles G.] Univ Calif Irvine, Sch Biol Sci, Dept Mol Biol & Biochem, Irvine, CA 92717 USA.
C3 University of Southern California; University of Southern California;
   University of Southern California; University of California System;
   University of California Santa Barbara; University of Texas System;
   University of Texas Medical Branch Galveston; Pennsylvania Commonwealth
   System of Higher Education (PCSHE); University of Pittsburgh; University
   of California System; University of California Irvine
RP Chen, J (通讯作者)，Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Cell & Neurobiol, 1501 San Pablo St,ZNI 227, Los Angeles, CA 90033 USA.
EM jeannie@usc.edu
RI Wetzel, Ronald/G-7453-2011
FU National Eye Institute in the form of a Vision Core [EY03040]; National
   Institutes of Health [R01 NS46356, NIH R01 EY11527, NIH R24 EY017404];
   Arnold and Mabel Beckman Foundation; Larry L. Hillblom Foundation;
   NATIONAL EYE INSTITUTE [P30EY003040, R01EY011527, R24EY017404,
   R01EY012155] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   NEUROLOGICAL DISORDERS AND STROKE [R01NS046356] Funding Source: NIH
   RePORTER
FX Supported by the National Eye Institute in the form of a Vision Core
   Grant to Doheny Eye Institute (EY03040) and National Institutes of
   Health Grants R01 NS46356 (RW), NIH R01 EY11527 (LVJ), and NIH R24
   EY017404 (LVJ); a grant from the Arnold and Mabel Beckman Foundation
   (RL, JC); and a Network Grant from the Larry L. Hillblom Foundation
   (CGG, RL, JC).
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NR 39
TC 109
Z9 116
U1 0
U2 10
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 2010
VL 51
IS 3
BP 1304
EP 1310
DI 10.1167/iovs.09-4207
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 563VW
UT WOS:000275164300011
PM 19892876
OA Green Accepted, Green Published
DA 2022-11-30
ER

PT J
AU Tuo, JS
   Ross, RJ
   Herzlich, AA
   Shen, DF
   Ding, XY
   Zhou, M
   Coon, SL
   Hussein, N
   Salem, N
   Chan, CC
AF Tuo, Jingsheng
   Ross, Robert J.
   Herzlich, Alexandra A.
   Shen, Defen
   Ding, Xiaoyan
   Zhou, Min
   Coon, Steven L.
   Hussein, Nahed
   Salem, Norman, Jr.
   Chan, Chi-Chao
TI A High Omega-3 Fatty Acid Diet Reduces Retinal Lesions in a Murine Model
   of Macular Degeneration
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; PIGMENT EPITHELIUM;
   PROSTAGLANDIN D-2; GENE-EXPRESSION; GROWTH-FACTOR; INFLAMMATION; RAT;
   MACROPHAGES; MICE
AB Age-related macular degeneration (AMD) is one of the leading cause of blindness among the elderly; however, current therapy options are limited. Epidemiological studies have shown that a diet that is high in omega-3 polyunsaturated (n-3) fatty acids can slow disease progression in patients with advanced AMD. In this study, we evaluated the effect of such a diet on the retinas of Ccl2(-1-1)/Cx3cr1(-/-) mice, a model that develops AMD-like retinal lesions that Include focal deep retinal lesions, abnormal retinal pigment epithelium, photoreceptor degeneration, and A2E accumulation. Ccl2(-/-)/Cx3crl(-/-) mice that ingested a high n-3 fatty acid diet showed a slower progression of retinal lesions compared with the low n-3 fatty acids group. Some mice that were given high levels of n-3 fatty acids had lesion reversion. We found a shunted arachidonic acid metabolism that resulted in decreased pro-inflammatory derivatives (prostaglandin E-2 and leukotriene B-4 ) and an increased anti-inflammatory derivative (prostaglandin D-2). We also measured lower ocular TNF-alpha and IL-6 transcript levels in the mice fed a diet of high n-3 fatty acids. Our findings in these mice are in line with human studies of AMD risk reduction by long-chain n-3 fatty acids. This murine model provides a useful tool to evaluate therapies that might delay the development of AMD. (Am J Pathol 2009, 175:799-807; DOI: 10.2353/ajpath.2009.090089)
C1 [Chan, Chi-Chao] NEI, NIH, Immunopathol Sect, Immunol Lab, Bethesda, MD 20892 USA.
   [Coon, Steven L.] NICHHD, Sect Neuroendocrinol, Bethesda, MD 20892 USA.
   [Hussein, Nahed; Salem, Norman, Jr.] NIAAA, NIH, Bethesda, MD USA.
   [Hussein, Nahed; Salem, Norman, Jr.] Lab Membrane Biochem & Biophys, Bethesda, MD USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); National Institutes of Health (NIH) - USA; NIH Eunice Kennedy
   Shriver National Institute of Child Health & Human Development (NICHD);
   National Institutes of Health (NIH) - USA; NIH National Institute on
   Alcohol Abuse & Alcoholism (NIAAA)
RP Chan, CC (通讯作者)，NEI, NIH, Immunopathol Sect, Immunol Lab, 10-10N 103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
RI Hussein, Nahed/AAL-1240-2020
OI Hussein, Nahed/0000-0001-5113-105X; Tuo, Jingsheng/0000-0002-1372-7810
FU Intramural Research Program of the National Eye Institute; National
   Institutes of Health; American Health Assistance Foundation; NATIONAL
   EYE INSTITUTE [ZIAEY000418, Z01EY000418, Z01EY000222, ZICEY000461,
   Z01EY000461, ZIAEY000222] Funding Source: NIH RePORTER
FX Supported by the Intramural Research Program of the National Eye
   Institute, National Institutes of Health and the American Health
   Assistance Foundation.
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NR 45
TC 60
Z9 64
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD AUG
PY 2009
VL 175
IS 2
BP 799
EP 807
DI 10.2353/ajpath.2009.090089
PG 9
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 477GZ
UT WOS:000268508500031
PM 19608872
OA Green Published
DA 2022-11-30
ER

PT J
AU Ramo, K
   Cashman, SM
   Kumar-Singh, R
AF Ramo, Kasmir
   Cashman, Siobhan M.
   Kumar-Singh, Rajendra
TI Evaluation of adenovirus-delivered human CD59 as a potential therapy for
   AMD in a model of human membrane attack complex formation on murine RPE
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID HOMOLOGOUS SPECIES RESTRICTION; RETINAL-PIGMENT EPITHELIUM; FACTOR-H
   POLYMORPHISM; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION;
   FACTOR-B; REGULATORY PROTEINS; DRUSEN FORMATION; GENE-TRANSFER; SOLUBLE
   CD59
AB PURPOSE. Complement-mediated damage to the retinal pigment epithelium (RPE), Bruch membrane, and choroid has been associated with pathogenesis in age-related macular degeneration (AMD). The terminal step of complement activation involves lysis of cells by the insertion of the membrane attack complex (MAC) in the plasma membrane. The hypothesis that local overexpression of human CD59 (hCD59) delivered by an adenovirus (Ad) vector to primary murine RPE cells in vitro, RPE in vivo, or cornea ex vivo protects those cells from human MAC deposition and lysis was tested.
   METHODS. A humanized model of MAC deposition on murine cells and murine ocular tissues including RPE and cornea was developed to permit testing of human complement regulators in mice. A recombinant adenovirus-expressing hCD59 was generated, and this virus was injected into the subretinal space of adult mice. Subsequently, eyecups from these mice were exposed to human serum, and the levels of MAC deposition on the RPE were quantified. hCD59 was also expressed on murine cornea ex vivo and in murine hepatocytes, and primary RPE cells in vitro and levels of human MAC deposition and cell lysis were measured.
   RESULTS. Adenovirus-mediated delivery of hCD59 to the RPE, cornea, or cells in culture protects those cells from human MAC deposition and MAC-mediated damage and vesiculation.
   CONCLUSIONS. The humanized model of MAC deposition on murine ocular tissues allows testing of human complement regulators that may have potential in the treatment of AMD or other diseases associated with complement activation.
C1 [Ramo, Kasmir; Cashman, Siobhan M.; Kumar-Singh, Rajendra] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
C3 Tufts University
RP Kumar-Singh, R (通讯作者)，Tufts Univ, Sch Med, Dept Ophthalmol, 136 Harrison Ave, Boston, MA 02111 USA.
EM rajendra.kumar-singh@tufts.edu
OI Kumar-Singh, Rajendra/0000-0002-7754-0713
FU Ellison Foundation; National Institutes of Health/National Eye Institute
   [EY014991, EY013887]; Foundation Fighting Blindness; Lions Eye
   Foundation, and Research to Prevent Blindness; NATIONAL EYE INSTITUTE
   [R01EY013837, R01EY021805, R01EY014991] Funding Source: NIH RePORTER
FX Supported by the Ellison Foundation, National Institutes of
   Health/National Eye Institute Grants EY014991 and EY013887, Foundation
   Fighting Blindness, Lions Eye Foundation, and Research to Prevent
   Blindness grants to the Tufts University Department of Ophthalmology.
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NR 46
TC 28
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
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD SEP
PY 2008
VL 49
IS 9
BP 4126
EP 4136
DI 10.1167/iovs.08-2025
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 344AB
UT WOS:000258896500052
PM 18487376
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Sivaprakasam, M
   Liu, WT
   Wang, GX
   Weiland, JD
   Humayun, MS
AF Sivaprakasam, M
   Liu, WT
   Wang, GX
   Weiland, JD
   Humayun, MS
TI Architecture tradeoffs in high-density micro stimulators for retinal
   prosthesis
SO IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS I-REGULAR PAPERS
LA English
DT Article
DE biomedical; functional electrical stimulation (FES); implantable
   devices; microstimulator; retinal prosthesis
ID ELECTRICAL-STIMULATION; MORPHOMETRIC-ANALYSIS; RETINITIS-PIGMENTOSA;
   VISUAL-PERCEPTION; PERFORMANCE; DESIGN
AB Electrical stimulation of the retinal layer inside the eye has been identified as a form of visual prosthesis to restore lost vision in blind patients affected by retinitis pigmentosa and age-related macular degeneration, through several studies and experiments. While initial clinical experiments using retinal prosthesis have resulted in visual perception in humans, psychophysical tests and simulations suggest that a high-density retinal prosthesis is required to restore vision to a level of reading and mobility. In the implanted prosthetic device, the microstimulator is functionally the closest to the tissue, delivering the electrical stimulation. Choosing the suitable architecture of the microstimulator requires the knowledge of the available choices and the tradeoffs associated with each of them. This paper presents the different architectures of microstimulator for high-density retinal prosthesis considering both the biomedical and circuit perspectives. The choices for the key aspects of the microstimulator-location of the chip in the eye, electrode configuration, method of stimulation, demultiplexing, stimulation sequence, and communication protocol-are discussed along with the associated tradeoffs for each of them. One of the architectures is used in a prototype microstimulator for an implantable epi-retinal prosthetic device to be used in clinical trials. The chip consists of 60 independently programmable output drivers for delivering electrical stimulus and digital controller for managing run-time and configuration data. The circuit details of the chip fabricated in 1.2-mu m CMOS technology and its measurement results are presented.
C1 Univ Calif Santa Cruz, Dept Elect Engn, Santa Cruz, CA 95064 USA.
   Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90089 USA.
C3 University of California System; University of California Santa Cruz;
   University of Southern California
RP Sivaprakasam, M (通讯作者)，Univ Calif Santa Cruz, Dept Elect Engn, Santa Cruz, CA 95064 USA.
EM mohan@soe.ucsc.edu
OI Weiland, James/0000-0003-3453-9074; Sivaprakasam,
   Mohanasankar/0000-0002-6714-9147
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NR 28
TC 49
Z9 56
U1 0
U2 6
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1549-8328
EI 1558-0806
J9 IEEE T CIRCUITS-I
JI IEEE Trans. Circuits Syst. I-Regul. Pap.
PD DEC
PY 2005
VL 52
IS 12
BP 2629
EP 2641
DI 10.1109/TCSI.2005.857554
PG 13
WC Engineering, Electrical & Electronic
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA 993HV
UT WOS:000233946100014
DA 2022-11-30
ER

PT J
AU Pianta, MJ
   Aleman, TS
   Cideciyan, AV
   Sunness, JS
   Li, YY
   Campochiaro, BA
   Campochiaro, PA
   Zack, DJ
   Stone, EM
   Jacobson, SG
AF Pianta, MJ
   Aleman, TS
   Cideciyan, AV
   Sunness, JS
   Li, YY
   Campochiaro, BA
   Campochiaro, PA
   Zack, DJ
   Stone, EM
   Jacobson, SG
TI In vivo micropathology of Best macular dystrophy with optical coherence
   tomography
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Best macular dystrophy; bestrophin; macular degeneration; optical
   coherence tomography; retinal pigment epithelium; VMD2
ID CENTRAL SEROUS CHORIORETINOPATHY; GENE; MUTATIONS; BESTROPHIN; DISEASE;
   VMD2; PROTEIN
AB Best macular dystrophy (BMD) is an autosomal dominant retinopathy caused by mutations in the VMD2 gene that encodes a chloride channel in the basolateral membrane of the retinal pigment epithelium (RPE). BMD patients were studied using optical coherence tomography (OCT) to understand the disease process in the macula leading to vision loss. BMD patients (ages 5-61), representing four families with known VMD2 mutations, were included. OCT scans were recorded in the central retina and longitudinal reflectivity profiles were analysed. The central retina in BMD showed different OCT abnormalities at or near the level of the highly reflective deep retinal band termed the outer retina-choroid complex (ORCC). Two types of ORCC change were noted to occur either separately or together: (1) splitting with or without intervening hyporeflective areas; and (2) elevation. Longitudinal study of a BMD patient indicated that such abnormalities were dynamic and changed in type and degree with time. The pathogenetic sequence in BMD may begin with defective fluid transport across the RPE secondary to the channelopathy in the basolateral membrane. In the macula, this leads to an abnormal interface with adjacent structures at both apical and basal surfaces of the RPE. The disease process results in detachments of the neurosensory retina, such as in central serous chorioretinopathy, and sub-RPE pathology resembling some stages of age-related macular degeneration, with eventual loss of photoreceptors, inner retina and central vision. (C) 2003 Elsevier Science Ltd. All rights reserved.
C1 Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   Johns Hopkins Univ Hosp, Sch Med, Dept Ophthalmol & Neurosci, Baltimore, MD 21287 USA.
   Johns Hopkins Univ Hosp, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21287 USA.
   Univ Iowa Hosp & Clin, Dept Ophthalmol, Iowa City, IA 52242 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; Johns Hopkins
   University; Johns Hopkins Medicine; Johns Hopkins University; Johns
   Hopkins Medicine; University of Iowa
RP Pianta, MJ (通讯作者)，Univ Melbourne, Dept Optometry & Vis Sci, Cnr Keppel & Cardigan St, Carlton, Vic 3053, Australia.
RI Cideciyan, Artur V/A-1075-2007
OI Cideciyan, Artur V/0000-0002-2018-0905; Sunness,
   Janet/0000-0001-8823-0780; Jacobson, Samuel/0000-0003-2122-169X; Stone,
   Edwin M./0000-0003-3343-4414; Zack, Don/0000-0002-7966-1973; Pianta,
   Michael/0000-0003-1781-4855
FU NEI NIH HHS [EY-13203, EY-13365, EY-05627] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [R01EY005627, R01EY013203] Funding Source: NIH
   RePORTER
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NR 37
TC 46
Z9 49
U1 0
U2 1
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2003
VL 76
IS 2
BP 203
EP 211
DI 10.1016/S0014-4835(02)00280-4
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 646KQ
UT WOS:000181034500009
PM 12565808
DA 2022-11-30
ER

PT J
AU Fisher, CRR
   Ebeling, MCC
   Ferrington, DAA
AF Fisher, Cody R. R.
   Ebeling, Mara C. C.
   Ferrington, Deborah A. A.
TI Quantification of mitophagy using mKeima-mito in cultured human primary
   retinal pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
ID PROGRESSIVE STAGES; OXIDATIVE STRESS; AGE; PROTEOMICS; AUTOPHAGY
AB The retinal pigment epithelium is a pigmented monolayer of cells that help maintain a healthy retina. Loss of this essential cell layer is implicated in a number of visual disorders, including age-related macular degeneration (AMD). Utilizing primary RPE cultures to investigate disease is an important step in understanding disease mechanisms. However, the use of primary RPE cultures presents a number of challenges, including the limited number of cells available and the presence of auto-fluorescent pigment that interferes with quantifying fluorescent probes. Additionally, primary RPE are difficult to transfect with exogenous nucleic acids traditionally used for fluorescent imaging. To overcome these challenges, we used an adeno-associated viral (AAV) vector to express a pH sensitive fluorescent protein, mKeima, fused to the mitochondrial targeting sequence of cytochrome oxidase subunit 8A (mKeima-mito). mKeima-mito allows for quantification of mitochondrial autophagy (mitophagy) in live-cell time-lapse imaging experiments. We also developed an image analysis pipeline to selectively quantify mKeima-mito while removing the signal of auto-fluorescent pigment from the dataset by utilizing information from the mKeima fluorescent channels. These techniques are demonstrated in primary RPE cultures expressing mKeima-mito treated with 2-[2-[4-(trifluoromethoxy)phenyl]hydrazinylidene]-propanedinitrile (FCCP), an uncoupler that depolarizes the mitochondrial membrane and leads to mitochondrial fragmentation and mitophagy. The techniques outlined provide a roadmap for investigating disease mechanisms or the effect of treatments utilizing fluorescent probes in an important cell culture model.
C1 [Fisher, Cody R. R.; Ebeling, Mara C. C.; Ferrington, Deborah A. A.] Univ Minnesota, Dept Ophthalmol & Visual Neurosci, Minneapolis, MN 55455 USA.
   [Fisher, Cody R. R.; Ferrington, Deborah A. A.] Univ Minnesota, Grad Program Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities;
   University of Minnesota System; University of Minnesota Twin Cities
RP Ferrington, DAA (通讯作者)，Univ Minnesota, Dept Ophthalmol & Visual Neurosci, Minneapolis, MN 55455 USA.
EM ferri013@umn.edu
OI Ferrington, Deborah/0000-0003-2561-7464
FU NIH/National Eye Institute [F31-EY031558, T32-EY025187, R01EY026012,
   R01EY028554]; NIH/National Institute on Aging [T32-AG029796]; Diana
   Jacobs Kalman/AFAR Scholarships for Research in the Biology of Aging;
   VitreoRetinal Surgery Foundation Fellowship; Elaine and Robert Larson
   Endowed Vision Chair; Lindsay Family Foundation
FX The authors wish to acknowledge the contribution of the Lions Gift of
   Sight (St. Paul, MN) personnel for their assistance in procuring the
   eyes and processing eye tissue. The authors also thank the donors and
   their families for their essential contributions to the research. This
   work was supported in part by NIH/National Eye Institute (F31-EY031558
   (to CRF) , T32-EY025187 (to CRF) , R01EY026012 and R01EY028554 (to DAF)
   ) , NIH/National Institute on Aging (T32-AG029796 (to CRF) ) , Diana
   Jacobs Kalman/AFAR Scholarships for Research in the Biology of Aging (to
   CRF) , VitreoRetinal Surgery Foundation Fellowship (to CRF) , the Elaine
   and Robert Larson Endowed Vision Chair, the Lindsay Family Foundation,
   and an anonymous benefactor for AMD research.
CR Bonilha VL, 2008, CLIN OPHTHALMOL, V2, P413
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NR 34
TC 1
Z9 1
U1 2
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 APR
PY 2022
VL 217
AR 108981
DI 10.1016/j.exer.2022.108981
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZQ2IV
UT WOS:000766935100001
PM 35167864
DA 2022-11-30
ER

PT J
AU Hao, SF
   Bai, JY
   Liu, HM
   Wang, LJ
   Liu, T
   Lin, CB
   Luo, XG
   Gao, JH
   Zhao, JM
   Li, HL
   Tang, H
AF Hao, Shaofeng
   Bai, Junye
   Liu, Huimin
   Wang, Lijun
   Liu, Tao
   Lin, Chaobin
   Luo, Xiangguang
   Gao, Junhui
   Zhao, Jiangman
   Li, Huilin
   Tang, Hui
TI Comparison of machine learning tools for the prediction of AMD based on
   genetic, age, and diabetes-related variables in the Chinese population
SO REGENERATIVE THERAPY
LA English
DT Article
DE AMD; SNPs; Age; Diabetes; Machine learning tools
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; GENOME-WIDE ASSOCIATION; MACULAR
   DEGENERATION; RISK-FACTORS; LOC387715 GENE; US TWIN; MACULOPATHY;
   SUSCEPTIBILITY; POLYMORPHISMS; SMOKING
AB Introduction: Age-related macular degeneration (AMD) is the main cause of visual impairment and the most important cause of blindness in older people. However, there is currently no effective treatment for this disease, so it is necessary to establish a risk model to predict AMD development.
   Methods: This study included a total of 202 subjects, comprising 82 AMD patients and 120 control subjects. Sixty-six single-nucleotide polymorphisms (SNPs) were identified using the MassArray assay. Considering 14 independent clinical variables as well as SNPs, four predictive models were established in the training set and evaluated by the confusion matrix, area under the receiver operating characteristic (ROC) curve (AUROC). The difference distributions of the 14 independent clinical features between the AMD and control groups were tested using the chi-squared test. Age and diabetes were adjusted using logistic regression analysis and the "genomic-control" method was used for multiple testing correction.
   Results: Three SNPs (rs10490924, OR = 1.686, genomic-control corrected p-value (GC) = 0.030; rs2338104, OR = 1.794, GC = 0.025 and rs1864163, OR = 2.125, GC = 0.038) were significant risk factors for AMD development. In the training set, four models obtained AUROC values above 0.72.
   Conclusions: We believe machine learning tools will be useful for the early prediction of AMD and for the development of relevant intervention strategies. (C) 2020, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.
C1 [Hao, Shaofeng; Li, Huilin] Changzhi Med Coll, Dept Ophthalmol, Heji Hosp, 271 Taihang East St, Changzhi 046011, Peoples R China.
   [Bai, Junye] Shanxi Med Univ, Gen Hosp Tisco, Dept Ophthalmol, Hosp 6, Taiyuan 030008, Peoples R China.
   [Liu, Huimin; Wang, Lijun; Luo, Xiangguang; Gao, Junhui; Zhao, Jiangman; Tang, Hui] Shanghai Biotecan Pharmaceut Co Ltd, 180 Zhangheng Rd, Shanghai 201204, Peoples R China.
   [Liu, Huimin; Wang, Lijun; Luo, Xiangguang; Gao, Junhui; Zhao, Jiangman; Tang, Hui] Shanghai Zhangjiang Inst Med Innovat, Shanghai 201204, Peoples R China.
   [Liu, Tao] Xi An Jiao Tong Univ, Aviat Hanzhong Hosp 3201, Dept Ophthalmol, Hanzhong 723000, Peoples R China.
   [Lin, Chaobin] Fujian Med Univ, Dept Ophthalmol, Hosp Quanzhou 1, Quanzhou 362000, Peoples R China.
C3 Changzhi Medical College; Shanxi Medical University; Xi'an Jiaotong
   University; Fujian Medical University
RP Li, HL (通讯作者)，Changzhi Med Coll, Dept Ophthalmol, Heji Hosp, 271 Taihang East St, Changzhi 046011, Peoples R China.; Tang, H (通讯作者)，Shanghai Biotecan Pharmaceut Co Ltd, 180 Zhangheng Rd, Shanghai 201204, Peoples R China.
EM 88935560@qq.com; tang11_23@126.com
RI Zhao, Jiangman/AAR-1726-2020
FU Major Projects of Special Development Funds in Zhangjiang National
   Independent Innovation Demonstration Zone, Shanghai [ZJ2017-ZD-012]
FX This work was supported by the Major Projects of Special Development
   Funds in Zhangjiang National Independent Innovation Demonstration Zone,
   Shanghai (ZJ2017-ZD-012).
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NR 71
TC 2
Z9 2
U1 4
U2 7
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 2352-3204
J9 REGEN THER
JI Regen. Ther.
PD DEC
PY 2020
VL 15
BP 180
EP 186
DI 10.1016/j.reth.2020.09.001
PG 7
WC Cell & Tissue Engineering; Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Engineering
GA PH7XP
UT WOS:000600620800024
PM 33426217
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Schafer, N
   Wolf, HN
   Enzbrenner, A
   Schikora, J
   Reichenthaler, M
   Enzmann, V
   Pauly, D
AF Schaefer, Nicole
   Wolf, Hannah N.
   Enzbrenner, Anne
   Schikora, Juliane
   Reichenthaler, Maria
   Enzmann, Volker
   Pauly, Diana
TI Properdin Modulates Complement Component Production in Stressed Human
   Primary Retinal Pigment Epithelium Cells
SO ANTIOXIDANTS
LA English
DT Article
DE retinal pigment epithelium; complement system; properdin; AMD-risk
   genotype; intracellular; cell-associated; inflammasome; oxidative
   stress; human
ID OXIDATIVE STRESS; MACULAR DEGENERATION; FACTOR-H; RPE CELLS;
   GENE-EXPRESSION; DOWN-REGULATION; C3; ACTIVATION; C5A; PATHWAY
AB The retinal pigment epithelium (RPE) maintains visual function and preserves structural integrity of the retina. Chronic dysfunction of the RPE is associated with retinal degeneration, including age-related macular degeneration (AMD). The AMD pathogenesis includes both increased oxidative stress and complement dysregulation. Physiological sources of oxidative stress in the retina are well known, while complement sources and regulation are still under debate. Using human primary RPE (hpRPE) cells, we have established a model to investigate complement component expression on transcript and protein level in AMD-risk and non-risk hpRPE cells. We evaluated the effect of properdin, a complement stabilizer, on the hpRPE cell-dependent complement profile exposed to oxidative stress. hpRPE cells expressed complement components, receptors and regulators. Complement proteins were also stored and secreted by hpRPE cells. We associated AMD-risk single nucleotide polymorphisms with an increased secretion of complement factors D (CFD) and I (CFI). Furthermore, we detected hpRPE cell-associated complement activation products (C3a, C5a) independent of any extracellularly added complement system. Exogenous properdin increased the mRNA expression ofCFIandCFD, but decreased levels of complement components (C1Q,C3), receptors (C3AR,C5AR1,CD11B) and inflammation-associated transcripts (NLRP3,IL1B) in hpRPE cells exposed to oxidative stress. This properdin effect was time-dependently counter regulated. In conclusion, our data unveiled a local, genotype-associated complement component production in hpRPE cells, regulated by exogenous properdin. The local complement production and activation via blood-independent mechanisms can be a new therapeutic target for AMD.
C1 [Schaefer, Nicole; Wolf, Hannah N.; Enzbrenner, Anne; Schikora, Juliane; Reichenthaler, Maria; Pauly, Diana] Univ Hosp Regensburg, Expt Ophthalmol, Eye Clin, D-93053 Regensburg, Germany.
   [Enzmann, Volker] Univ Bern, Univ Hosp Bern, Dept Ophthalmol, CH-3010 Bern, Switzerland.
   [Enzmann, Volker] Univ Bern, Dept Biomed Res, CH-3010 Bern, Switzerland.
C3 University of Regensburg; University of Bern; University Hospital of
   Bern; University of Bern
RP Pauly, D (通讯作者)，Univ Hosp Regensburg, Expt Ophthalmol, Eye Clin, D-93053 Regensburg, Germany.
EM Nicole.Schaefer@vkl.uni-regensburg.de;
   Hannah.Wolf@stud.uni-regensburg.de; A.enzbrenner@googlemail.com;
   Juliane.Schikora@stud.uni-regensburg.de;
   Maria.reichenthaler@googlemail.com; Volker.Enzmann@insel.ch;
   Diana.Pauly@ukr.de
FU Velux Foundation [1103]
FX This research was funded by the Velux Foundation (Proj. Nr. 1103) to
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NR 84
TC 8
Z9 8
U1 1
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD SEP
PY 2020
VL 9
IS 9
AR 793
DI 10.3390/antiox9090793
PG 19
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 OE9UX
UT WOS:000580867800001
PM 32859013
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Powell, W
   Powell, V
   Cook, M
AF Powell, Wendy
   Powell, Vaughan
   Cook, Marc
TI The Accessibility of Commercial Off-The-Shelf Virtual Reality for Low
   Vision Users: A Macular Degeneration Case Study
SO CYBERPSYCHOLOGY BEHAVIOR AND SOCIAL NETWORKING
LA English
DT Article
DE VR; low vision; AMD; macular degeneration; accessibility; COTS
ID MAGNIFICATION
AB Virtual reality (VR) is demonstrating increasing potential for therapeutic benefit in elderly care, but it is still generally considered to be the domain of the visually unimpaired. Even where VR and augmented reality (AR) are being explored for use with low vision, it is generally with a focus on creating bespoke software and hardware. However, the properties of commercial off-the-shelf (COTS) headsets, such as high luminance, may render them accessible even to very low vision users. Using a case-study approach, we explored the differences in visual perception from baseline to pass-through AR and commercial VR applications for an elderly female (Mrs. M) with advanced age-related macular degeneration. We found notable improvements in object, face, and color recognition, particularly with higher display brightness. Furthermore, Mrs. M was able to engage fully and enthusiastically with a number of (unmodified) VR applications, providing detailed descriptions of both static and moving elements. We suggest that the high luminance available in COTS VR may support more stable fixation closer to the fovea, improving visual resolution. Furthermore, the improvements we noted in color perception support previous suggestions that increasing luminance may improve photosensitivity by reducing the uptake of limited oxygen by the rod cells. We conclude that low vision should not automatically preclude users from engaging in VR research or entertainment, and that they may be able to use well-illuminated VR applications without any special modifications.
C1 [Powell, Wendy; Powell, Vaughan] Tilburg Univ, Sch Humanities & Digital Sci, Dept Cognit Sci & Artificial Intelligence, Dante Bldg,Room D 346, NL-5037 AB Tilburg, Netherlands.
   [Cook, Marc] Univ Portsmouth, Fac Creat & Cultural Ind, Portsmouth, Hants, England.
C3 Tilburg University; University of Portsmouth
RP Powell, W (通讯作者)，Tilburg Univ, Sch Humanities & Digital Sci, Dept Cognit Sci & Artificial Intelligence, Dante Bldg,Room D 346, NL-5037 AB Tilburg, Netherlands.
EM w.a.powell@uvt.nl
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NR 22
TC 1
Z9 1
U1 1
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2152-2715
EI 2152-2723
J9 CYBERPSYCH BEH SOC N
JI Cyberpsychology Behav. Soc. Netw.
PD MAR 1
PY 2020
VL 23
IS 3
BP 185
EP 191
DI 10.1089/cyber.2019.0409
EA FEB 2020
PG 7
WC Psychology, Social
WE Social Science Citation Index (SSCI)
SC Psychology
GA LB8NJ
UT WOS:000515342700001
PM 32091918
DA 2022-11-30
ER

PT J
AU Sasaki, F
   Koga, T
   Ohba, M
   Saeki, K
   Okuno, T
   Ishikawa, K
   Nakama, T
   Nakao, S
   Yoshida, S
   Ishibashi, T
   Ahmadieh, H
   Kanavi, MR
   Hafezi-Moghadam, A
   Penninger, JM
   Sonoda, KH
   Yokomizo, T
AF Sasaki, Fumiyuki
   Koga, Tomoaki
   Ohba, Mai
   Saeki, Kazuko
   Okuno, Toshiaki
   Ishikawa, Keijiro
   Nakama, Takahito
   Nakao, Shintaro
   Yoshida, Shigeo
   Ishibashi, Tatsuro
   Ahmadieh, Hamid
   Kanavi, Mozhgan Rezaei
   Hafezi-Moghadam, Ali
   Penninger, Josef M.
   Sonoda, Koh-Hei
   Yokomizo, Takehiko
TI Leukotriene B-4 promotes neovascularization and macrophage recruitment
   in murine wet-type AMD models
SO JCI INSIGHT
LA English
DT Article
ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; TUMOR-ASSOCIATED MACROPHAGES;
   OXYGEN-INDUCED RETINOPATHY; T-CELL PROLIFERATION; DIET-INDUCED OBESITY;
   MACULAR DEGENERATION; INSULIN-RESISTANCE; M2 MACROPHAGES; MOUSE MODEL;
   12-HYDROXYHEPTADECATRIENOIC ACID
AB Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is associated with aging and is a leading cause of blindness worldwide. Here, we demonstrate that leukotriene B-4(LTB4) receptor 1 (BLT1) promotes laser-induced choroidal neovascularization (CNV) in a mouse model for wet-type AMD. CNV was significantly less in BLT1-deficient (BLT1-K0) mice compared with BLT1-WT controls. Expression of several proangiogenic and profibrotic factors was lower in BLT1-KO eyes than in BLT1-WT eyes. LTB4 production in the eyes was substantially increased in the early phase after laser injury. BLT1 was highly expressed in M2 macrophages in vitro and in vivo, and ocular BLT1(+) M2 macrophages were increased in the aged eyes after laser injury. Furthermore, M2 macrophages were rapidly attracted by LTB4 and subsequently produced VEGF-A- through BLT1-mediated signaling. Consequently, intravitreal injection of M2 macrophages augmented ENV formation, which was attenuated by BLT1 deficiency. Thus, laser-induced injury to the retina triggered LTB4 production and attracted M2 macrophages via BLT1, leading to development of CNV. A selective BLT1 antagonist (CP105696) and 3 LTB4 inhibitors (zileuton, MK-886, and bestatin) reduced CNV in a dose-dependent manner. CP105696 also inhibited the accumulation of BLT1(+) M2 macrophages in the laser-injured eyes of aged mice. Together, these results indicate that the LTB4-BLT1 axis is a potentially novel therapeutic target for CNV of wet-type AMD.
C1 [Sasaki, Fumiyuki; Koga, Tomoaki; Ohba, Mai; Saeki, Kazuko; Okuno, Toshiaki; Yokomizo, Takehiko] Juntendo Univ, Dept Biochem, Sch Med, Tokyo, Japan.
   [Ishikawa, Keijiro; Nakama, Takahito; Nakao, Shintaro; Yoshida, Shigeo; Ishibashi, Tatsuro; Sonoda, Koh-Hei] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Japan.
   [Ahmadieh, Hamid] Shahid Beheshti Univ Med Sci, Ophthalm Res Ctr, Tehran, Iran.
   [Kanavi, Mozhgan Rezaei] Shahid Beheshti Univ Med Sci, Ocular Tissue Engn Res Ctr, Tehran, Iran.
   [Hafezi-Moghadam, Ali] Harvard Med Sch, Brigham & Womens Hosp, Mol Biomarkers Nanoimaging Lab, Boston, MA USA.
   [Hafezi-Moghadam, Ali] Harvard Med Sch, Dept Radiol, Boston, MA USA.
   [Penninger, Josef M.] Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna, Austria.
   [Koga, Tomoaki] Kumamoto Univ, Inst Mol Embryol & Genet, Dept Med Cell Biol, Kumamoto, Japan.
   [Sasaki, Fumiyuki] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Cell Signaling, Tokyo, Japan.
C3 Juntendo University; Kyushu University; Shahid Beheshti University
   Medical Sciences; Shahid Beheshti University Medical Sciences; Harvard
   University; Brigham & Women's Hospital; Harvard Medical School; Harvard
   University; Harvard Medical School; Austrian Academy of Sciences; Vienna
   Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); Kumamoto
   University; Tokyo Medical & Dental University (TMDU)
RP Yokomizo, T (通讯作者)，Juntendo Univ, Dept Biochem, Sch Med, Bunkyo Ku, Hongo 2-1-1, Tokyo 1138421, Japan.
EM yokomizo-tky@umin.ac.jp
RI Penninger, Josef M/I-6860-2013; Kanavi, Mozhgan Rezaei/AAX-9617-2020;
   Ahmadieh, Hamid/M-4853-2017; Yokomizo, Takehiko/P-5673-2016
OI Penninger, Josef M/0000-0002-8194-3777; Kanavi, Mozhgan
   Rezaei/0000-0002-1497-2260; Ahmadieh, Hamid/0000-0002-8139-2661;
   Yokomizo, Takehiko/0000-0002-5219-1553; Nakama,
   Takahito/0000-0001-8999-3667
FU Ministry of Education, Culture, Sports, Science, and Technology (MEXT)
   of the Japan Society for the Promotion of Science (JSPS) [22116001,
   22116002, 15H05897, 15H05904, 15H04708, 18H02627, 25860223, 15K19032,
   17K08664, 24590386, 15K08316, 18K06923, 25460374, 16K08596, 15KK0320];
   Naito Foundation; Ono Medical Research Foundation; Uehara Memorial
   Foundation; Mitsubishi Foundation; Takeda Science Foundation; Foundation
   for Strategic Research Projects in Private Universities of the MEXT
   [S1311011]; Institute for Environmental and Gender-Specific Medicine
FX This work was supported by Grants-in-Aid for Scientific Research
   (KAKENHI) from the Ministry of Education, Culture, Sports, Science, and
   Technology (MEXT) of the Japan Society for the Promotion of Science
   (JSPS) (grant nos. 22116001, 22116002, 15H05897, 15H05904, 15H04708, and
   18H02627 to TY; 25860223, 15K19032, and 17K08664 to TK; 24590386,
   15K08316, and 18K06923 to KS; and 25460374, 16K08596, and 15KK0320 to
   TO) and by grants from the Naito Foundation, the Ono Medical Research
   Foundation, the Uehara Memorial Foundation, the Mitsubishi Foundation,
   and the Takeda Science Foundation. This study was supported in part by a
   Grant-in-Aid (S1311011 to TY) from the Foundation for Strategic Research
   Projects in Private Universities of the MEXT and by a grant from the
   Institute for Environmental and Gender-Specific Medicine. We thank the
   Research Center for Human Disease Modeling (Kyushu University), the
   Research Support Center of the Division of Molecular and Biochemical
   Research (Juntendo University), and the Imaging Core Laboratory of the
   Institute of Medical Science (The University of Tokyo) for technical
   support. We also thank Eiichi Hasegawa (Harvard Medical School, Boston,
   Massachusetts, USA) and Akihiko Yoshimura (Keio University, Tokyo,
   Japan) for technical support of AMD model and BM transplantation, Takako
   Ichiki (California Institute of Technology, Pasadena, California, USA)
   for technical support of chemotaxis assay, and Miki Honda (Juntendo
   University), Akira Matsuda (Juntendo University), and the members of our
   laboratory for advice and helpful discussion.
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NR 95
TC 21
Z9 21
U1 0
U2 9
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD SEP 20
PY 2018
VL 3
IS 18
AR e96902
DI 10.1172/jci.insight.96902
PG 17
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA GU2QU
UT WOS:000445115700002
PM 30232269
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Real, JP
   Luna, JD
   Palma, SD
AF Real, J. P.
   Luna, J. D.
   Palma, S. D.
TI The reactivation time in the treatment of AMD: a forgotten key
   parameter?
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Time-to-treatment; Ranibizumab; Macular degeneration; Angiogenesis
   inhibitors/therapeutic use
ID MACULAR DEGENERATION; RANIBIZUMAB; REGIMEN
AB Objective Summarize and compare the available evidence on the reactivation times in patients with age-related macular degeneration treated with Ranibizumab (RNB).
   Method Systematic review of studies that reported the reactivation time of patients (direct method) or the number of injections received in a certain period of follow-up (indirect method).
   Results Only 18 of 89 selected studies reported the average reactivation time of patients in a manifest form, without the need of any calculation. The average calculated, weighted reactivation time was 101.8 days with the direct method and 99.8 days in the indirect method (84 studies included). With both methods, it was found that the average reactivation time of the RCTs was between 2 and 3 weeks less than the average time identified in the observational studies. These differences are also reflected in the clinical results, there being a correlation between the number of doses received and the change in BCVA. The analysis of 11 comparative studies showed a difference in reactivation times between patients treated with RNB or Bevacizumab (BVZ).
   Conclusion There are few direct studies of reactivation time, but calculation from the PRN dose number turns out to be a good approximation for retrospective study of the variable. The use of the PRN, with criteria not based on optical coherence tomography scans, delays the application of doses between 2 or 3 weeks, and patients suffer loss of clinical benefits. RNB enables patients to receive less injections than BVZ throughout treatment.
C1 [Real, J. P.; Palma, S. D.] Univ Nacl Cordoba, CONICET, Unidad Invest & Desarrollo Tecnol Farmaceut UNITE, Ciudad Univ, RA-5000 Cordoba, Argentina.
   [Real, J. P.; Palma, S. D.] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Ciencias Farmaceut, Ciudad Univ, RA-5000 Cordoba, Argentina.
   [Luna, J. D.] Ctr Privado Ojos Romagosa SA, Fdn VER, Vitreoretinal Dept, Dean Funes 429-432, Cordoba, Argentina.
C3 Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET);
   National University of Cordoba; National University of Cordoba
RP Palma, SD (通讯作者)，Univ Nacl Cordoba, CONICET, Unidad Invest & Desarrollo Tecnol Farmaceut UNITE, Ciudad Univ, RA-5000 Cordoba, Argentina.; Palma, SD (通讯作者)，Univ Nacl Cordoba, Fac Ciencias Quim, Dept Ciencias Farmaceut, Ciudad Univ, RA-5000 Cordoba, Argentina.
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NR 30
TC 2
Z9 2
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 JUN
PY 2018
VL 256
IS 6
BP 1079
EP 1087
DI 10.1007/s00417-018-3974-0
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GG1AY
UT WOS:000432412900006
PM 29675724
DA 2022-11-30
ER

PT J
AU Spaide, RF
   Fujimoto, JG
   Waheed, NK
   Sadda, SR
   Staurenghi, G
AF Spaide, Richard F.
   Fujimoto, James G.
   Waheed, Nadia K.
   Sadda, Srinivas R.
   Staurenghi, Giovanni
TI Optical coherence tomography angiography
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Multimodal imaging; Optical coherence tomography; Optical coherence
   tomography angiography
ID RETINAL-VEIN-OCCLUSION; FOVEAL AVASCULAR ZONE; SUBRETINAL DRUSENOID
   DEPOSITS; AGE-RELATED MACULOPATHY; DIABETIC MACULAR EDEMA;
   AMPLITUDE-DECORRELATION ANGIOGRAPHY; INTERCELLULAR-ADHESION MOLECULE-1;
   NEOVASCULARIZATION EARLY RESPONSE; INDOCYANINE GREEN ANGIOGRAPHY;
   NASCENT GEOGRAPHIC ATROPHY
AB Optical coherence tomography (OCT) was one of the biggest advances in ophthalmic imaging. Building on that platform, OCT angiography (OCTA) provides depth resolved images of blood flow in the retina and choroid with levels of detail far exceeding that obtained with older forms of imaging. This new modality is challenging because of the need for new equipment and processing techniques, current limitations of imaging capability, and rapid advancements in both imaging and in our understanding of the imaging and applicable pathophysiology of the retina and choroid. These factors lead to a steep learning curve, even for those with a working understanding dye-based ocular angiography. All for a method of imaging that is a little more than 10 years old. This review begins with a historical account of the development of OCTA, and the methods used in OCTA, including signal processing, image generation, and display techniques. This forms the basis to understand what OCTA images show as well as how image artifacts arise. The anatomy and imaging of specific vascular layers of the eye are reviewed. The integration of OCTA in multimodal imaging in the evaluation of retinal vascular occlusive diseases, diabetic retinopathy, uveitis, inherited diseases, age-related macular degeneration, and disorders of the optic nerve is presented. OCTA is an exciting, disruptive technology. Its use is rapidly expanding in clinical practice as well as for research into the pathophysiology of diseases of the posterior pole.
C1 [Spaide, Richard F.] Vitreous Retina Macula Consultants New York, 460 Pk Ave, New York, NY 10022 USA.
   [Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
   [Fujimoto, James G.] MIT, Res Lab Elect, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Waheed, Nadia K.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
   [Sadda, Srinivas R.] Univ Calif Los Angeles, Doheny Eye Inst, Los Angeles, CA USA.
   [Staurenghi, Giovanni] Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Eye Clin, Milan, Italy.
C3 Vitreous Retina Macula Consultants of New York; Massachusetts Institute
   of Technology (MIT); Massachusetts Institute of Technology (MIT); Tufts
   University; Doheny Eye Institute; University of California System;
   University of California Los Angeles; University of Milan; Luigi Sacco
   Hospital
RP Spaide, RF (通讯作者)，Vitreous Retina Macula Consultants New York, 460 Pk Ave, New York, NY 10022 USA.
EM rickspaide@gmail.com
RI Spaide, Richard/ABD-7368-2020; Staurenghi, Giovanni/K-4388-2017
OI Staurenghi, Giovanni/0000-0002-2299-5251
FU Macula Foundation, Inc. NY; National Institute of Health
   [R01-EY011289-30, R01-EY013178-18]; Air Force Office of Scientific
   Research [FA-9550-15-1-0473, FA9550-12-1-0499]; Macula Vision Research
   Foundation; Champalimaud Foundation; Beckman-Argyros Award in Vision
   Research; Massachusetts Lions Club; NATIONAL EYE INSTITUTE [R01EY011289,
   R01EY013178] Funding Source: NIH RePORTER
FX This work was supported in part by the Macula Foundation, Inc. NY,
   National Institute of Health contracts R01-EY011289-30, R01-EY013178-18,
   Air Force Office of Scientific Research contracts FA-9550-15-1-0473,
   FA9550-12-1-0499, the Macula Vision Research Foundation, the
   Champalimaud Foundation, the Beckman-Argyros Award in Vision Research
   and the Massachusetts Lions Club. We gratefully acknowledge Eric Moult
   for assistance with selected figures and editing portions of the text.
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NR 375
TC 703
Z9 719
U1 33
U2 196
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 2018
VL 64
BP 1
EP 55
DI 10.1016/j.preteyeres.2017.11.003
PG 55
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GK9AV
UT WOS:000436529700001
PM 29229445
OA hybrid, Green Published, Green Accepted
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Park, DW
   Mansberger, SL
AF Park, Dong-wouk
   Mansberger, Steven L.
TI Eye Disease in Patients with Diabetes Screened with Telemedicine
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE e-health; Ophthalmology; telehealth; telemedicine
ID RETINOPATHY; SPECIFICITY; SENSITIVITY; PREVALENCE
AB Background: Telemedicine with nonmydriatic cameras can detect not only diabetic retinopathy but also other eye disease. Objective: To determine the prevalence of eye diseases detected by telemedicine in a population with a high prevalence of minority and American Indian/Alaskan Native (AI/AN) ethnicities. Subjects and Methods: We recruited diabetic patients 18 years and older and used telemedicine with nonmydriatic cameras to detect eye disease. Two trained readers graded the images for diabetic retinopathy, age-related macular degeneration (ARMD), glaucomatous features, macular edema, and other eye disease using a standard protocol. We included both eyes for analysis and excluded images that were too poor to grade. Results: We included 820 eyes from 424 patients with 72.3% nonwhite ethnicity and 50.3% AI/AN heritage. While 283/424 (66.7%) patients had normal eye images, 120/424 (28.3%) had one disease identified; 15/424 (3.5%) had two diseases; and 6/424 (1.4%) had three diseases in one or both eyes. After diabetic retinopathy (104/424, 24.5%), the most common eye diseases were glaucomatous features (44/424, 10.4%) and dry ARMD (24/424, 5.7%). Seventeen percent (72/424, 17.0%) showed eye disease other than diabetic retinopathy. Conclusions: Telemedicine with nonmydriatic cameras detected diabetic retinopathy, as well as other visually significant eye disease. This suggests that a diabetic retinopathy screening program needs to detect and report other eye disease, including glaucoma and macular disease.
C1 [Park, Dong-wouk; Mansberger, Steven L.] Legacy Hlth, Legacy Devers Eye Inst, 1040 NW 22nd Ave,Suite 200, Portland, OR 97210 USA.
   [Park, Dong-wouk; Mansberger, Steven L.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
   [Mansberger, Steven L.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA.
C3 Devers Eye Institute; Legacy Health; Oregon Health & Science University;
   Oregon Health & Science University
RP Mansberger, SL (通讯作者)，Legacy Hlth, Legacy Devers Eye Inst, 1040 NW 22nd Ave,Suite 200, Portland, OR 97210 USA.
EM smansberger@deverseye.org
OI Mansberger, Steven/0000-0002-5208-3544
FU Centers for Disease Control and Prevention (CDC) [U48DP000024-01,
   1U48DP002673-01]; Good Samaritan Foundation at Legacy Health; Research
   to Prevent Blindness; NATIONAL CENTER FOR CHRONIC DISEASE PREV AND
   HEALTH PROMO [U48DP002673, U48DP000024] Funding Source: NIH RePORTER
FX This research was supported by grant funding from the Centers for
   Disease Control and Prevention (CDC U48DP000024-01 and 1U48DP002673-01),
   the Good Samaritan Foundation at Legacy Health, and Research to Prevent
   Blindness (unrestricted departmental funding to Casey Eye Institute).
   The authors appreciate the expertise of and data collection performed by
   Joann Malumaleumu, Ginny Rice, Laura Layland, and Susette Schwartz of
   the Hunter Health Clinic (Wichita, KS) and the Yellowhawk Tribal Health
   Center (Umatilla, OR).
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NR 18
TC 14
Z9 14
U1 0
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-5627
EI 1556-3669
J9 TELEMED E-HEALTH
JI Telemed. e-Health
PD FEB
PY 2017
VL 23
IS 2
BP 113
EP 118
DI 10.1089/tmj.2016.0034
PG 6
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA EL1BJ
UT WOS:000394355200007
PM 27328169
OA Green Published
DA 2022-11-30
ER

PT J
AU Giddabasappa, A
   Lalwani, K
   Norberg, R
   Gukasyan, HJ
   Paterson, D
   Schachar, RA
   Rittenhouse, K
   Klamerus, K
   Mosyak, L
   Eswaraka, J
AF Giddabasappa, Anand
   Lalwani, Kush
   Norberg, Rand
   Gukasyan, Hovhannes J.
   Paterson, David
   Schachar, Ronald A.
   Rittenhouse, Kay
   Klamerus, Karen
   Mosyak, Lydia
   Eswaraka, Jeetendra
TI Axitinib inhibits retinal and choroidal neovascularization in in vitro
   and in vivo models
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Axitinib; Small molecule receptor tyrosine kinase inhibitor; In vitro
   angiogenesis; 3D co-culture model; Rat choroidal neovascularization; Wet
   age-related macular degeneration
ID RECEPTOR TYROSINE KINASE; MACULAR DEGENERATION; OCULAR
   NEOVASCULARIZATION; MOLECULAR-MECHANISMS; ANGIOGENESIS; EFFICACY; CELLS;
   VEGF; MICE; PROLIFERATION
AB Age-related Macular Degeneration (AMD) is the leading cause of visual impairment and blindness in the elderly in developed countries. Neovascular/exudative (wet) AMD is the aggressive form of AMD and can involve choroidal neovascularization and vascular leakage. Anti-vascular endothelial growth factor (anti-VEGF) medications have significantly improved treatment of wet-AMD. However, only approximately 40% of patients obtain full benefit from anti-VEGF therapy and the medications are given by intravitreal injection. Axitinib, a small molecule multi-receptor tyrosine kinase inhibitor used for the treatment of advanced renal cell carcinoma, is taken orally and inhibits VEGF activity by blocking VEGF receptors. Axitinib also has the advantage of blocking platelet derived growth factor (PDGF) receptors which play a role in neovascularization. Using in vitro human retinal microvascular endothelial cells (HRMVECs), human brain vascular pericytes (HBVRs), 3D co-culture vessel sprout assay, and in vivo laser induced rat choroidal neovascularization (CNV) models, the effect of axitinib on neovascularization was evaluated. Axitinib inhibited neovascularization better than anti-VEGF and/or anti-hPDGF-B mAb in the in vitro models demonstrating that combined inhibition of both VEGF and PDGF pathways may be synergistic in treating wet-AMD. Additionally, axitinib showed good efficacy at a low dose (0.875 mg/day) in laser induced CNV model in rats. In conclusion our data shows that axitinib, an inhibitor of VEGF and PDGF-B pathways may be useful in ameliorating wet-AMD therapy. (C) 2016 PFIZER INC. Published by Elsevier Ltd.
C1 [Giddabasappa, Anand; Lalwani, Kush; Norberg, Rand; Paterson, David; Eswaraka, Jeetendra] Pfizer Inc, Global Sci & Technol WCM, 10724 Sci Ctr Dr, San Diego, CA 92121 USA.
   [Gukasyan, Hovhannes J.] Pfizer Inc, Pharmaceut Sci, 10724 Sci Ctr Dr, San Diego, CA 92121 USA.
   [Schachar, Ronald A.] Pfizer Inc, Global Clin Affairs, 10724 Sci Ctr Dr, San Diego, CA 92121 USA.
   [Rittenhouse, Kay] Pfizer Inc, External R&D Innovat, 10724 Sci Ctr Dr, San Diego, CA 92121 USA.
   [Klamerus, Karen] Pfizer Inc, Oncol Clin Dev, 10724 Sci Ctr Dr, San Diego, CA 92121 USA.
   [Mosyak, Lydia] Pfizer Inc, Global Biotherapeut Technol, 10724 Sci Ctr Dr, San Diego, CA 92121 USA.
C3 Pfizer; Pfizer; Pfizer; Pfizer; Pfizer; Pfizer
RP Giddabasappa, A; Eswaraka, J (通讯作者)，Pfizer Inc, Global Sci & Technol WCM, 10724 Sci Ctr Dr, San Diego, CA 92121 USA.; Giddabasappa, A; Eswaraka, J (通讯作者)，Pfizer Global Res & Dev, Global Sci & Technol WCM, 10724 Sci Ctr Dr, San Diego, CA 92121 USA.
EM anand.giddabasappa@pfizer.com; jeetendra.eswaraka@pfizer.com
RI Gukasyan, Hovhannes/AAX-8570-2020
FU Pfizer Inc.
FX We would like to thank Ken Geles (Pfizer-Oncology Research Unit) for
   suggestions on in vitro co-culture model and Yazdi Pithavala
   (Pfizer-Oncology Clinical Development) for suggestions on in vivo dose
   selection of Axitinib. The funding for this research and manuscript was
   provided by Pfizer Inc. All authors are currently or were in past
   employed by Pfizer Inc.
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U1 1
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 373
EP 379
DI 10.1016/j.exer.2016.02.010
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DL1DL
UT WOS:000375372300042
PM 26927930
OA hybrid
DA 2022-11-30
ER

PT J
AU Zanardi, I
   Borrelli, E
   Valacchi, G
   Travagli, V
   Bocci, V
AF Zanardi, I.
   Borrelli, E.
   Valacchi, G.
   Travagli, V.
   Bocci, V.
TI Ozone: A Multifaceted Molecule with Unexpected Therapeutic Activity
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Article
DE Ozone; Oxidants; Oxidative stress; Antioxidants; Hormesis; Body fluids
ID OXIDATIVE STRESS; IN-VIVO; REDOX HOMEOSTASIS; NITROUS-OXIDE; CELL-CYCLE;
   RESPONSES; EXPOSURE; LUNG; MECHANISMS; INDUCTION
AB A comprehensive outline for understanding and recommending the therapeutic use of ozone in combination with established therapy in diseases characterized by a chronic oxidative stress is currently available. The view of the absolute ozone toxicity is incorrect, because it has been based either on lung or on studies performed in artificial environments that do not correspond to the real antioxidant capacity of body compartments. In fact, ozone exerts either a potent toxic activity or it can stimulate biological responses of vital importance, analogously to gases with prospective therapeutic value such as NO, CO, H2S, H-2, as well as O-2 itself. Such a crucial difference has increasingly become evident during the last decade. The purpose of this review is to explain the aspects still poorly understood, highlighting the divergent activity of ozone on the various biological districts. It will be clarified that such a dual effect does not depend only upon the final gas concentration, but also on the particular biological system where ozone acts. The real significance of ozone as adjuvant therapeutic treatment concerns severe chronic pathologies among which are cardiovascular diseases, chronic obstructive pulmonary diseases, multiple sclerosis, and the dry form of age-related macular degeneration. It is time for a full insertion of ozone therapy within pharmaceutical sciences, responding to all the requirements of quality, efficacy and safety, rather than as either an alternative or an esoteric approach.
C1 [Zanardi, I.; Travagli, V.; Bocci, V.] Univ Siena, Dipartimento Biotecnol Chim & Farm, Viale Aldo Moro 2, I-53100 Siena, Italy.
   [Borrelli, E.] Univ Siena, Dipartimento Biotecnol Med, Str Scotte 4, I-53100 Siena, Italy.
   [Valacchi, G.] Univ Ferrara, Dipartimento Sci Vita & Biotecnol, Via Borsari 46, I-44121 Ferrara, Italy.
   [Valacchi, G.] Kyung Kee Univ, Deptartment Food & Nutr, Seoul, South Korea.
C3 University of Siena; University of Siena; University of Ferrara
RP Travagli, V (通讯作者)，Univ Siena, Viale Aldo Moro 2, I-53100 Siena, Italy.
EM valter.travagli@unisi.it
RI Borrelli, Emma/P-1018-2017; Borrelli, Emma/AAJ-8172-2021; Borrelli,
   Emma/AAE-7013-2019
OI Borrelli, Emma/0000-0002-4991-0289; Borrelli, Emma/0000-0002-4991-0289; 
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NR 114
TC 40
Z9 44
U1 1
U2 35
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 0929-8673
EI 1875-533X
J9 CURR MED CHEM
JI Curr. Med. Chem.
PY 2016
VL 23
IS 4
BP 304
EP 314
DI 10.2174/0929867323666151221150420
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
   Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA DG8JU
UT WOS:000372330900001
PM 26687830
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Cano, M
   Wang, L
   Wan, J
   Barnett, BP
   Ebrahimi, K
   Qian, J
   Handa, JT
AF Cano, Marisol
   Wang, Lei
   Wan, Jun
   Barnett, Bradley P.
   Ebrahimi, Katayoon
   Qian, Jiang
   Handa, James T.
TI Oxidative stress induces mitochondrial dysfunction and a protective
   unfolded protein response in RPE cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Aging-related disease; Epithelial-mesenchymal transition; ER stress;
   Mitochondria; Oxidative stress; Free radicals
ID ENDOPLASMIC-RETICULUM STRESS; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; CIGARETTE-SMOKE; GLUTATHIONE-PEROXIDASE;
   HEART-MITOCHONDRIA; POOLED FINDINGS; CHOP GADD153; 3 CONTINENTS;
   RISK-FACTORS
AB How cells degenerate from oxidative stress in aging-related disease is incompletely understood. This study's intent was to identify key cytoprotective pathways activated by oxidative stress and determine the extent of their protection. Using an unbiased strategy with microarray analysis, we found that retinal pigmented epithelial (RPE) cells treated with cigarette smoke extract (CSE) had overrepresented genes involved in the antioxidant and unfolded protein response (UPR). Differentially expressed antioxidant genes were predominantly located in the cytoplasm, with no induction of genes that neutralize superoxide and H-2-O-2 in the mitochondria, resulting in accumulation of superoxide and decreased ATP production. Simultaneously, CSE induced the UPR sensors IREl alpha, p-PERK, and ATP6, including CHOP, which was cytoprotective because CHOP knockdown decreased cell viability. In mice given intravitreal CSE, the RPE had increased IREla and decreased ATP and developed epithelial-mesenchymal transition, as suggested by decreased LRAT abundance, altered ZO-1 immunolabeling, and dysmorphic cell shape. Mildly degenerated RPE from early age-related macular degeneration (AMD) samples had prominent IREla, but minimal mitochondria! TOM20 immunolabeling. Although oxidative stress is thought to induce an antioxidant response with cooperation between the mitochondria and the ER, herein we show that mitochondria become impaired sufficiently to induce epithelial-mesenchymal transition despite a protective UPR. With similar responses in early AMD samples, these results suggest that mitochondria are vulnerable to oxidative stress despite a protective UPR during the early phases of aging-related disease. (c) 2014 Elsevier Inc. All rights reserved.
C1 [Cano, Marisol; Wang, Lei; Wan, Jun; Barnett, Bradley P.; Ebrahimi, Katayoon; Qian, Jiang; Handa, James T.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Handa, JT (通讯作者)，Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
EM jthanda@jhmi.edu
RI Barnett, Bradley/AAN-1628-2020; Wan, Jun/AAN-1337-2020; Wan,
   Jun/H-7132-2013; Wang, Lei/C-1902-2015
OI Barnett, Bradley/0000-0002-8301-404X; Wan, Jun/0000-0001-9286-6562; Wan,
   Jun/0000-0001-9286-6562; Wang, Lei/0000-0002-7957-1003
FU NIH [EY019904, P30EY001765]; Thome Foundation [EY14005]; Research to
   Prevent Blindness Senior Scientist Award; Robert Bond Welch
   Professorship; Research to Prevent Blindness; NATIONAL EYE INSTITUTE
   [R01EY019904, R01EY014005, P30EY001765] Funding Source: NIH RePORTER
FX Funding for this work was provided by NIH EY019904 (J.T.H.), the Thome
   Foundation (J.T.H.), EY14005 (J.T.H.), a Research to Prevent Blindness
   Senior Scientist Award (J.T.H.), an unrestricted grant from Research to
   Prevent Blindness to the Wilmer Eye Institute, an NIH P30EY001765 core
   grant, the Robert Bond Welch Professorship, and a gift from the Merlau
   family.
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NR 46
TC 64
Z9 67
U1 1
U2 34
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD APR
PY 2014
VL 69
BP 1
EP 14
DI 10.1016/j.freeradbiomed.2014.01.004
PG 14
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA AD8BC
UT WOS:000333490500001
PM 24434119
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Nadri, S
   Yazdani, S
   Arefian, E
   Gohari, Z
   Eslaminejad, MB
   Kazemi, B
   Soleimani, M
AF Nadri, Samad
   Yazdani, Shahin
   Arefian, Ehsan
   Gohari, Zahra
   Eslaminejad, Mohamadreza Baghaban
   Kazemi, Bahram
   Soleimani, Masoud
TI Mesenchymal stem cells from trabecular meshwork become
   photoreceptor-like cells on amniotic membrane
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Photoreceptor; Mesenchymal stem cell; Amniotic membrane; Trabecular
   meshwork; Differentiation; In vitro
ID RETINAL PROGENITOR CELLS; MARROW STROMAL CELLS; ADULT MAMMALIAN EYE;
   TRANSPLANTATION; DIFFERENTIATION; BONE; RECONSTRUCTION; FIBROBLASTS;
   THERAPY; GROWTH
AB Stem cell therapy is a promising approach for treatment of degenerative retinal disorders such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In this study, human mesenchymal stem cells (MSCs) were isolated from the trabecular meshwork (TM), the major functional tissue of the anterior chamber angle in the eye, were characterized and differentiated into photoreceptor cells on amniotic membrane (AM). After isolation of trabecular meshwork and culture of the stromal segment of this tissue, fibroblast-like cells (CD105(+), CD90(+), CD44(+), CD166(+) cells) capable of differentiation toward mesenchymal and photoreceptor lineages were obtained. The isolated cells were seeded on amniotic membrane and were treated with induction medium. Immunocytochemistry and quantitative real time RT-PCR (qPCR) were used to detect expression of photoreceptor genes such as rhodopsin, recoverin, CRX, and peripherin; and the bipolar cell marker protein kinase C alpha (PKC-alpha). As a result, immunocytochemistry revealed that the differentiated TMMSCs expressed rhodopsin, CRX and PKC proteins. qPCR showed the expression of rhodopsin (rod like photoreceptor-specific marker), and CRX genes were significantly higher in TMMSCs differentiated on AM than those differentiated on tissue culture polystyrene (TCPS). In conclusion, our findings suggested that a combination of TMMSCs (as a new source) and basement membrane support from AM might be a suitable source of cells for subretinal transplantation in regenerative therapy for retinal disorders such as AMD and RP. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Nadri, Samad] Shahid Beheshti Univ Med Sci, Fac Med, Med Phys & Biomed Engn Dept, Tehran, Iran.
   [Nadri, Samad] Shahid Beheshti Univ Med Sci, Student Res Comm, Tehran, Iran.
   [Yazdani, Shahin] Shahid Beheshti Univ Med Sci, Ophthalm Res Ctr, Tehran, Iran.
   [Arefian, Ehsan] Stem Cell Technol Res Ctr, Dept Mol Biol & Genet Engn, Tehran, Iran.
   [Gohari, Zahra] Stem Cell Technol Res Ctr, Stem Cell Biol Dept, Tehran, Iran.
   [Eslaminejad, Mohamadreza Baghaban] ACECR, Rayon Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Stem Cell & Dev Biol, Tehran, Iran.
   [Kazemi, Bahram] Shahid Beheshti Univ Med Sci, Dept Biotechnol, Fac Med, Tehran, Iran.
   [Kazemi, Bahram] Shahid Beheshti Univ Med Sci, Cellular & Mol Biol Res Ctr, Tehran, Iran.
   [Soleimani, Masoud] Tarbiat Modares Univ, Fac Med Sci, Dept Hematol, Tehran, Iran.
C3 Shahid Beheshti University Medical Sciences; Shahid Beheshti University
   Medical Sciences; Shahid Beheshti University Medical Sciences; Academic
   Center for Education, Culture & Research (ACECR); Shahid Beheshti
   University Medical Sciences; Shahid Beheshti University Medical
   Sciences; Tarbiat Modares University
RP Soleimani, M (通讯作者)，Tarbiat Modares Univ, Fac Med Sci, Dept Hematol, Tehran, Iran.
EM bahram_14@yahoo.com; Soleim_m@modares.ac.ir
RI Kazemi, Bahram/F-2785-2016; Eslaminejad, Mohamadreza
   Baghaban/S-3645-2017; Yazdani, Shahin/AAW-5387-2020; Kazemi,
   Bahram/GRR-9838-2022; Arfiane, Ehsan/N-3912-2017; Nadri,
   Samad/N-4548-2016; Nadri, Samad/M-9349-2016
OI Kazemi, Bahram/0000-0002-3072-8831; Eslaminejad, Mohamadreza
   Baghaban/0000-0002-1036-0072; Arfiane, Ehsan/0000-0002-0758-4710; Nadri,
   Samad/0000-0002-2710-3128; Yazdani, Shahin/0000-0002-9583-1434; Nadri,
   Samad/0000-0002-1523-3152
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NR 28
TC 44
Z9 48
U1 0
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD APR 29
PY 2013
VL 541
BP 43
EP 48
DI 10.1016/j.neulet.2012.12.055
PG 6
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 138SX
UT WOS:000318531400010
PM 23403103
DA 2022-11-30
ER

PT J
AU Burt, AJ
   Caston, L
   Leeson, S
   Shelp, BJ
   Lee, EA
AF Burt, Andrew J.
   Caston, Linda
   Leeson, Steven
   Shelp, Barry J.
   Lee, Elizabeth A.
TI Development and Utilization of High Carotenoid Maize Germplasm: Proof of
   Concept
SO CROP SCIENCE
LA English
DT Article
ID MACULAR PIGMENT; BETA-CAROTENE; GENETIC-VARIATION; LUTEIN; EGGS;
   QUANTIFICATION
AB Lutein and zeaxanthin are commonly referred to as the macular carotenoids, as they are localized to ocular tissues and their loss is associated with age-related macular degeneration. High carotenoid eggs have been suggested as a good dietary source of macular carotenoids, particularly lutein. In this paper we demonstrate two key proof of concept steps: transferring the high carotenoid phenotype to elite inbred backgrounds and carotenoid enrichment of eggs through feeding high carotenoid maize (Zea mays L.) grain to laying hens (Gallus domesticus). Using two inbred backgrounds and three high carotenoid donor lines, BC1S2 lines were developed with selections made based solely on visual assessment of kernel color. The 20-wk laying hen feeding trial consisted of four complete diets that varied for the maize component (i.e., a high-zeaxanthin maize line, a high-lutein maize line, and a conventional yellow maize line with and without a commercial lutein [Oro-glo] supplement) with eggs samples collected every 4 wk. High-carotenoid maize diet treatments yielded carotenoid concentrations in egg yolks that were approximately fourfold higher than those achieved with the conventional maize feed control and were found to be equally available to the laying hen as a lutein feed additive used as a positive control. While phenotyping by high pressure liquid chromatography (HPLC) cannot be completely eliminated, visual selection increases the proportion of high-carotenoid phenotypes and it appears that transferring the high carotenoid phenotype into elite inbred lines is relatively straightforward.
C1 [Burt, Andrew J.; Lee, Elizabeth A.] Univ Guelph, Dept Plant Agr, Guelph, ON N1G 2W1, Canada.
   [Caston, Linda; Leeson, Steven] Univ Guelph, Dept Anim & Poultry Sci, Guelph, ON N1G 2W1, Canada.
   [Shelp, Barry J.] Univ Guelph, Dept Plant Agr, Guelph, ON N1G 2W1, Canada.
C3 University of Guelph; University of Guelph; University of Guelph
RP Lee, EA (通讯作者)，Univ Guelph, Dept Plant Agr, Crop Sci Bldg, Guelph, ON N1G 2W1, Canada.
EM lizlee@uoguelph.ca
FU Natural Sciences and Engineering Research Council of Canada; Ontario
   Ministry of Agriculture, Food and Rural Affairs; Egg Farmers of Canada;
   Grain Farmers of Ontario; Canadian Foundation for Innovation; Ontario
   Innovative Trust
FX A.J. Burt and E. A. Lee, University of Guelph, Department of Plant
   Agriculture, Crop Science Building, Guelph, ON, N1G 2W1 Canada; L.
   Caston and S. Leeson, University of Guelph, Department of Animal and
   Poultry Science, Building #70, Guelph, ON, N1G 2W1 Canada; B.J. Shelp,
   University of Guelph, Department of Plant Agriculture, Edmund C. Bovey
   Building, Guelph, ON, N1G 2W1 Canada. Financial support from the Natural
   Sciences and Engineering Research Council of Canada, Ontario Ministry of
   Agriculture, Food and Rural Affairs, Egg Farmers of Canada, Grain
   Farmers of Ontario, Canadian Foundation for Innovation, and Ontario
   Innovative Trust is acknowledged. Received 2 Feb. 2012.
   <SUP>star</SUP>Corresponding author (lizlee@uoguelph.ca).
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NR 36
TC 10
Z9 10
U1 0
U2 14
PU CROP SCIENCE SOC AMER
PI MADISON
PA 677 S SEGOE ROAD, MADISON, WI 53711 USA
SN 0011-183X
EI 1435-0653
J9 CROP SCI
JI Crop Sci.
PD MAR
PY 2013
VL 53
IS 2
BP 554
EP 563
DI 10.2135/cropsci2012.02.0069
PG 10
WC Agronomy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Agriculture
GA 099MC
UT WOS:000315624600022
DA 2022-11-30
ER

PT J
AU Singh, MS
   Issa, PC
   Butler, R
   Martin, C
   Lipinski, DM
   Sekaran, S
   Barnard, AR
   MacLaren, RE
AF Singh, Mandeep S.
   Issa, Peter Charbel
   Butler, Rachel
   Martin, Chris
   Lipinski, Daniel M.
   Sekaran, Sumathi
   Barnard, Alun R.
   MacLaren, Robert E.
TI Reversal of end-stage retinal degeneration and restoration of visual
   function by photoreceptor transplantation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE stem cell; blindness; retinal surgery; visual cortex; neural
   regeneration
ID LEBER CONGENITAL AMAUROSIS; PUPILLARY LIGHT REFLEX; MOUSE RETINA;
   STEM-CELLS; PRECURSORS; MICE; INTEGRATION; EXPRESSION; MEMBRANE;
   DISRUPTION
AB One strategy to restore vision in retinitis pigmentosa and age-related macular degeneration is cell replacement. Typically, patients lose vision when the outer retinal photoreceptor layer is lost, and so the therapeutic goal would be to restore vision at this stage of disease. It is not currently known if a degenerate retina lacking the outer nuclear layer of photoreceptor cells would allow the survival, maturation, and reconnection of replacement photoreceptors, as prior studies used hosts with a preexisting outer nuclear layer at the time of treatment. Here, using a murine model of severe human retinitis pigmentosa at a stage when no host rod cells remain, we show that transplanted rod precursors can reform an anatomically distinct and appropriately polarized outer nuclear layer. A trilaminar organization was returned to rd1 hosts that had only two retinal layers before treatment. The newly introduced precursors were able to resume their developmental program in the degenerate host niche to become mature rods with light-sensitive outer segments, reconnecting with host neurons downstream. Visual function, assayed in the same animals before and after transplantation, was restored in animals with zero rod function at baseline. These observations suggest that a cell therapy approach may reconstitute a light-sensitive cell layer de novo and hence repair a structurally damaged visual circuit. Rather than placing discrete photoreceptors among preexisting host outer retinal cells, total photoreceptor layer reconstruction may provide a clinically relevant model to investigate cell-based strategies for retinal repair.
C1 [Singh, Mandeep S.; Issa, Peter Charbel; Butler, Rachel; Lipinski, Daniel M.; Sekaran, Sumathi; Barnard, Alun R.; MacLaren, Robert E.] Univ Oxford, Nuffield Dept Clin Neurosci, Nuffield Lab Ophthalmol, Oxford OX3 9DU, England.
   [Martin, Chris] Univ Oxford, Gray Inst Radiat Oncol & Biol, Oxford OX3 7DQ, England.
   [MacLaren, Robert E.] Moorfields Eye Hosp Fdn Trust, London EC1V 2PD, England.
   [MacLaren, Robert E.] UCL, Natl Inst Hlth Res, Biomed Res Ctr, Inst Ophthalmol, London EC1V 2PD, England.
   [MacLaren, Robert E.] Oxford Univ Hosp NHS Trust, Oxford Eye Hosp, Oxford OX3 9DU, England.
   [MacLaren, Robert E.] Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX3 9DU, England.
C3 University of Oxford; University of Oxford; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   University of London; University College London; Oxford University
   Hospitals NHS Foundation Trust; University of Oxford
RP MacLaren, RE (通讯作者)，Univ Oxford, Nuffield Dept Clin Neurosci, Nuffield Lab Ophthalmol, Oxford OX3 9DU, England.
EM enquiries@eye.ox.ac.uk
RI Issa, Peter Charbel/O-2580-2019; Issa, Peter Charbel/E-8935-2018; Singh,
   Mandeep/AAS-8842-2021
OI Issa, Peter Charbel/0000-0002-0351-6673; Issa, Peter
   Charbel/0000-0002-0351-6673; Singh, Mandeep/0000-0003-1749-0088;
   Lipinski, Daniel/0000-0001-7828-614X; MacLaren,
   Robert/0000-0002-3096-4682; Martin, Chris/0000-0002-8186-784X
FU National Institute for Health Research Biomedical Research Centres at
   Oxford University Hospitals NHS Trust; Moorfields Eye Hospital; UK
   Medical Research Council; Wellcome Trust; Health Foundation; Royal
   College of Surgeons of Edinburgh; Royal Society; Fight for Sight;
   Lanvern Foundation; Special Trustees of Moorfields Eye Hospital; Oxford
   Stem Cell Institute; BBSRC [BB/G003602/1] Funding Source: UKRI; MRC
   [G0601588] Funding Source: UKRI; Biotechnology and Biological Sciences
   Research Council [BB/G003602/1] Funding Source: researchfish
FX We thank Anand Swaroop for supplying Tg(Nrl-E-GFP) mice and Shankar
   Srivinas, Stuart Peirson, Carina Pothecary, Wayne Davies, Stephen
   Hughes, and Qisheng You for their kind assistance. This research was
   supported by the National Institute for Health Research Biomedical
   Research Centres at Oxford University Hospitals NHS Trust and Moorfields
   Eye Hospital, the UK Medical Research Council, the Wellcome Trust, the
   Health Foundation, the Royal College of Surgeons of Edinburgh, the Royal
   Society, Fight for Sight, the Lanvern Foundation, the Special Trustees
   of Moorfields Eye Hospital, and the Oxford Stem Cell Institute. M. S. S.
   was supported by the Singapore National Medical Research Council and the
   Department of Ophthalmology, National University Hospital, Singapore.
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NR 36
TC 169
Z9 178
U1 0
U2 51
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 15
PY 2013
VL 110
IS 3
BP 1101
EP 1106
DI 10.1073/pnas.1119416110
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 075TI
UT WOS:000313909100066
PM 23288902
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Tilleul, J
   Querques, G
   Canoui-Poitrine, F
   Leveziel, N
   Souied, EH
AF Tilleul, Julien
   Querques, Giuseppe
   Canoui-Poitrine, Florence
   Leveziel, Nicolas
   Souied, Eric H.
TI Assessment of a Spectral Domain OCT Segmentation Software in a
   Retrospective Cohort Study of Exudative AMD Patients
SO OPHTHALMOLOGICA
LA English
DT Article
DE Optical coherence tomography; Age-related macular degeneration; Pigment
   epithelium detachment
ID OPTICAL COHERENCE TOMOGRAPHY; RETINAL THICKNESS MEASUREMENTS; MACULAR
   DEGENERATION; CIRRUS OCT; HIGH-SPEED; RANIBIZUMAB; DISEASES
AB Background: To assess the ability of the Spectralis optical coherence tomography (OCT) segmentation software to identify the inner limiting membrane and Bruch's membrane in exudative age-related macular degeneration (AMD) patients. Methods: Thirty-eight eyes of 38 naive exudative AMD patients were retrospectively included. They all had a complete ophthalmologic examination including Spectralis OCT at baseline, at month 1 and 2. Reliability of the segmentation software was assessed by 2 ophthalmologists. Reliability of the segmentation software was defined as good if both inner limiting membrane and Bruch's membrane were correctly drawn. Results: A total of 38 patients charts were reviewed (114 scans). The inner limiting membrane was correctly drawn by the segmentation software in 114/114 spectral domain OCT scans (100%). Conversely, Bruch's membrane was correctly drawn in 59/114 scans (51.8%). The software was less reliable in locating Bruch's membrane in case of pigment epithelium detachment (PED) than without PED (42.5 vs. 73.5%, respectively; p = 0.049), but its reliability was not associated with SRF or CME (p = 0.55 and p = 0.10, respectively). Conclusion: Segmentation of the inner limiting membrane was constantly trustworthy but Bruch's membrane segmentation was poorly reliable using the automatic Spectrails segmentation software. Based on this software, evaluation of retinal thickness may be incorrect, particularly in case of PED. PED is effectively an important parameter which is not included when measuring retinal thickness. Copyright (C) 2012 S. Karger AG, Basel
C1 [Tilleul, Julien; Querques, Giuseppe; Leveziel, Nicolas; Souied, Eric H.] Hop Intercommunal Creteil, Serv Ophtalmol, FR-94010 Creteil, France.
   [Canoui-Poitrine, Florence] Hop Henri Mondor, Serv Sante Publ, F-94010 Creteil, France.
   [Querques, Giuseppe; Canoui-Poitrine, Florence; Leveziel, Nicolas; Souied, Eric H.] Univ Paris Est Creteil, Creteil, France.
   [Canoui-Poitrine, Florence] Univ Paris Est Creteil, LIC, EA 4393, Creteil, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil;
   Assistance Publique Hopitaux Paris (APHP); Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); Hopital Universitaire
   Henri-Mondor - APHP; Universite Paris-Est-Creteil-Val-de-Marne (UPEC);
   Universite Paris-Est-Creteil-Val-de-Marne (UPEC)
RP Tilleul, J (通讯作者)，Hop Intercommunal Creteil, Serv Ophtalmol, 40 Ave Verdun, FR-94010 Creteil, France.
EM julien.tilleul@gmail.com
RI Canoui-Poitrine, Florence/R-4474-2018
OI Canoui-Poitrine, Florence/0000-0001-9970-6051; Querques,
   Giuseppe/0000-0002-3292-9581; Nicolas, Leveziel/0000-0001-8533-9457
CR Brown DM, 2006, NEW ENGL J MED, V355, P1432, DOI 10.1056/NEJMoa062655
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NR 28
TC 4
Z9 4
U1 0
U2 6
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
EI 1423-0267
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2013
VL 229
IS 2
BP 80
EP 85
DI 10.1159/000342980
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 085NO
UT WOS:000314621700003
PM 23171503
DA 2022-11-30
ER

PT J
AU Meyer, CH
   Holz, FG
AF Meyer, C. H.
   Holz, F. G.
TI Preclinical aspects of anti-VEGF agents for the treatment of wet AMD:
   ranibizumab and bevacizumab
SO EYE
LA English
DT Article
DE age-related macular degeneration; ranibizumab; bevacizumab; Lucentis;
   Avastin; VEGF
ID ENDOTHELIAL GROWTH-FACTOR; VERTEPORFIN PHOTODYNAMIC THERAPY; RETINAL
   GANGLION-CELLS; PIGMENT EPITHELIAL TEARS; UNTREATED FELLOW EYE; MACULAR
   DEGENERATION; INTRAVITREAL BEVACIZUMAB; CRYSTAL-STRUCTURE; VITREOUS
   LEVELS; PHARMACOKINETICS
AB Three anti-vascular endothelial growth factor (VEGF) therapies are currently used for the treatment of patients with wet age-related macular degeneration (AMD): pegaptanib, ranibizumab, and bevacizumab. Ranibizumab is an antibody fragment approved for the treatment of wet AMD. Bevacizumab is a full-length antibody registered for use in oncology but unlicensed for wet AMD. However, it is used off-label worldwide not only for wet AMD but also for various other ocular diseases associated with macular edema and abnormal vessel growth. We consider aspects of ranibizumab and bevacizumab in relation to their molecular characteristics, in vitro and in vivo properties, and preclinical safety data. Before 2009, most studies described the short-term toxicity of bevacizumab in multiple cell types of the eye. Since 2009, an increasing number of studies have compared the properties of ranibizumab and bevacizumab and investigated their impact on retinal cell functioning. Compared with bevacizumab, ranibizumab neutralizes VEGF better at low concentrations, maintains efficacy for longer, and has a higher retinal penetration and potency. Studies in animals demonstrate ranibizumab to be better localized to the injected eye, whereas bevacizumab appears to have a greater effect in the fellow eye. In humans, a localized and systemic effect has been reported for both molecules. In conclusion, overlapping yet distinct pharmacological properties of ranibizumab and bevacizumab indicate that safety or efficacy data from one cannot be extrapolated to the other. Eye (2011) 25, 661-672; doi:10.1038/eye.2011.66; published online 1 April 2011
C1 [Meyer, C. H.; Holz, F. G.] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Nordrhein Westf, Germany.
C3 University of Bonn
RP Meyer, CH (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Nordrhein Westf, Germany.
EM meyer_eye@yahoo.com
RI Meyer, Carsten/A-3981-2017
OI Meyer, Carsten/0000-0002-0530-5298
FU Novartis Pharma AG, Basel, Switzerland
FX We acknowledge Matthew Cunningham of Alpha-Plus Medical Communications
   Ltd., UK, who provided medical writing services, with funding from
   Novartis Pharma AG, Basel, Switzerland. This service encompassed the
   preparation of a first draft, editing, checking content and language,
   formatting, referencing, preparing tables and figures, and incorporating
   the authors' revisions, all carried out under our direction. At all
   stages, we had control over the content of this manuscript, for which we
   have given final approval and taken full responsibility.
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   AVASTIN AVASTIN PRES
NR 94
TC 94
Z9 98
U1 0
U2 24
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 2011
VL 25
IS 6
BP 661
EP 672
DI 10.1038/eye.2011.66
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 775BA
UT WOS:000291430100001
PM 21455242
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Gupta, P
   Yee, KMP
   Garcia, P
   Rosen, RB
   Parikh, J
   Hageman, GS
   Sadun, AA
   Sebag, J
AF Gupta, Priya
   Yee, Kenneth M. P.
   Garcia, Patricia
   Rosen, Richard B.
   Parikh, Jignesh
   Hageman, Gregory S.
   Sadun, Alfredo A.
   Sebag, J.
TI Vitreoschisis in macular diseases
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; POSTERIOR VITREOSCHISIS; HOLE; HYALOCYTES
AB Objectives Vitreoschisis is a possible pathogenic mechanism in macular diseases. Thus, the vitreoretinal interface was evaluated in monkey eyes and patients with various macular diseases in search of vitreoschisis. It is hypothesised that vitreoschisis is present in macular holes (MH) and macular pucker (MP), but not in other maculopathies.
   Methods Histopathology was studied in 14 monkey eyes and a vitrectomy specimen of a patient with macular pucker. Optical coherence tomography/scanning laser ophthalmoscopy (OCT/SLO) was performed in 239 eyes: 45 MH, 45 MP, 51 dry age-related macular degeneration (AMD), 53 non-proliferative diabetic retinopathy (NPDR) and 45 controls.
   Results Immunohistochemistry demonstrated lamellae in the posterior vitreous cortex of 12/14 (86%) monkey eyes. With OCT/SLO, vitreoschisis was detected in 24/45 (53%) MH and 19/45 (42%) MP eyes, but in only 7/53 (13%) NPDR, 3/51 (6%) AMD and 3/45 (7%) control eyes (p<0.001 for all comparisons). Rejoining of the inner and outer walls of the split posterior vitreous cortex was visible in 16/45 (36%) MH eyes and 15/45 (33%) MP eyes. Histopathology of the MP specimen confirmed a split with rejoining in the posterior vitreous cortex.
   Conclusions Vitreoschisis was detected in half of eyes with MH and MP, but much less frequently in controls, AMD and NPDR patients. These findings suggest that anomalous PVD with vitreoschisis may be pathogenic in MH and MP.
C1 [Gupta, Priya; Yee, Kenneth M. P.; Sebag, J.] VMR Inst, Huntington Beach, CA 92647 USA.
   [Gupta, Priya; Yee, Kenneth M. P.; Sadun, Alfredo A.; Sebag, J.] USC, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA USA.
   [Garcia, Patricia; Rosen, Richard B.] New York Eye & Ear Infirm, New York, NY 10003 USA.
   [Hageman, Gregory S.] Univ Utah, Salt Lake City, UT USA.
C3 Doheny Eye Institute; University of Southern California; University of
   Southern California Keck Hospital; New York Eye & Ear Infirmary of Mount
   Sinai; Utah System of Higher Education; University of Utah
RP Sebag, J (通讯作者)，VMR Inst, 7677 Ctr Ave,Suite 400, Huntington Beach, CA 92647 USA.
EM jsebag@vmrinstitute.com
RI Sebag, J./AAF-3602-2020; Gupta, Priya/GRX-2614-2022
OI Sebag, J/0000-0001-8648-5747
FU OPKO Instrumentation, LLC; NATIONAL EYE INSTITUTE [R01EY011515,
   P30EY014800] Funding Source: NIH RePORTER
FX RBR has financial affiliations with OPKO Instrumentation, LLC.
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NR 25
TC 79
Z9 81
U1 0
U2 5
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 2011
VL 95
IS 3
BP 376
EP 380
DI 10.1136/bjo.2009.175109
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 722NY
UT WOS:000287440400015
PM 20584710
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Schloendorn, J
   Webb, T
   Kemmish, K
   Hamalainen, M
   Jackemeyer, D
   Jiang, LJ
   Mathieu, J
   Rebo, J
   Sankman, J
   Sherman, L
   Tontson, L
   Qureshi, A
   Alvarez, P
   Rittmann, B
AF Schloendorn, John
   Webb, Tim
   Kemmish, Kent
   Hamalainen, Mark
   Jackemeyer, David
   Jiang, Lijing
   Mathieu, Jacques
   Rebo, Justin
   Sankman, Jonathan
   Sherman, Lindsey
   Tontson, Lauri
   Qureshi, Ateef
   Alvarez, Pedro
   Rittmann, Bruce
TI Medical Bioremediation: A Concept Moving Toward Reality
SO REJUVENATION RESEARCH
LA English
DT Article
ID ENZYME REPLACEMENT THERAPY; PIGMENTED EPITHELIAL-CELLS; MACROPHAGE FOAM
   CELLS; LIPOFUSCIN FLUOROPHORE; MACULAR DEGENERATION; RECOMBINANT ENZYME;
   STARGARDTS-DISEASE; STORAGE DISORDER; MANNOSE RECEPTOR; AGALSIDASE-BETA
AB A major driver of aging is catabolic insufficiency, the inability of our bodies to break down certain substances that accumulate slowly throughout the life span. Even though substance buildup is harmless while we are young, by old age the accumulations can reach a toxic threshold and cause disease. This includes some of the most prevalent diseases in old age-atherosclerosis and macular degeneration. Atherosclerosis is associated with the buildup of cholesterol and its oxidized derivatives (particularly 7-ketocholesterol) in the artery wall. Age-related macular degeneration is associated with carotenoid lipofuscin, primarily the pyridinium bisretinoid A2E. Medical bioremediation is the concept of reversing the substance accumulations by using enzymes from foreign species to break down the substances into forms that relieve the disease-related effect. We report on an enzyme discovery project to survey the availability of microorganisms and enzymes with these abilities. We found that such microorganisms and enzymes exist. We identified numerous bacteria having the ability to transform cholesterol and 7-ketocholesterol. Most of these species initiate the breakdown by same reaction mechnism as cholesterol oxidase, and we have used this enzyme directly to reduce the toxicity of 7-ketocholesterol, the major toxic oxysterol, to cultured human cells. We also discovered that soil fungi, plants, and some bacteria possess peroxidase and carotenoid cleavage oxygenase enzymes that effectively destroy with varied degrees of efficiency and selectivity the carotenoid lipofuscin found in macular degeneration.
C1 [Schloendorn, John; Webb, Tim; Rebo, Justin] SENS Fdn Res Ctr, Sunnyvale, CA 94089 USA.
   [Schloendorn, John; Jackemeyer, David; Jiang, Lijing; Sankman, Jonathan; Sherman, Lindsey; Tontson, Lauri; Rittmann, Bruce] Arizona State Univ, Biodesign Inst, Tempe, AZ USA.
   [Kemmish, Kent; Hamalainen, Mark] Halcyon Mol, Redwood Shores, CA USA.
   [Mathieu, Jacques; Alvarez, Pedro] Rice Univ, Dept Civil & Environm Engn, Houston, TX USA.
   [Rebo, Justin; Qureshi, Ateef] St Georges Univ, Sch Med, Dept Microbiol, Grenada, WI USA.
C3 SENS Research Foundation; Arizona State University; Arizona State
   University-Tempe; Rice University; St. George's University
RP Schloendorn, J (通讯作者)，SENS Fdn Res Ctr, 1230 Bordeaux, Sunnyvale, CA 94089 USA.
EM zauberkugel@gmail.com
RI Alvarez, Pedro/AAE-7216-2019
OI Alvarez, Pedro/0000-0002-6725-7199; Mathieu, Jacques/0000-0003-1776-8772
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NR 55
TC 13
Z9 13
U1 0
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1549-1684
EI 1557-8577
J9 REJUV RES
JI Rejuv. Res.
PD DEC
PY 2009
VL 12
IS 6
BP 411
EP 419
DI 10.1089/rej.2009.0917
PG 9
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA 538JO
UT WOS:000273180600005
PM 20041735
DA 2022-11-30
ER

PT J
AU Ito, A
   Hibino, E
   Kobayashi, C
   Terasaki, H
   Kagami, H
   Ueda, M
   Kobayashi, T
   Honda, H
AF Ito, A
   Hibino, E
   Kobayashi, C
   Terasaki, H
   Kagami, H
   Ueda, M
   Kobayashi, T
   Honda, H
TI Construction and delivery of tissue-engineered human retinal pigment
   epithelial cell sheets, using magnetite nanoparticles and magnetic force
SO TISSUE ENGINEERING
LA English
DT Article
ID INTRACELLULAR HYPERTHERMIA; CATIONIC LIPOSOMES; TRANSPLANTATION;
   HEAT-SHOCK-PROTEIN-70; NEOVASCULARIZATION; DEGENERATION; THERAPY
AB Choroidal neovascularization (CNV) is the most severe form of age-related macular degeneration (AMD), which causes rapid visual loss. Transplantation of cultured retinal pigment epithelium (RPE) cell sheet by tissue engineering is a possible approach to the treatment of CNV. In the present study, we investigated the possibility of using magnetite nanoparticles and magnetic force to construct and deliver RPE cell sheets in vitro. When magnetite cationic liposomes (MCLs), having a positive charge at the surface, were added to ARPE-19 human RPE cells at a concentration of 25 or 50 pg of magnetite per cell, the cells took up 40 to 55% of the MCLs. The magnetically labeled ARPE-19 cells (8 x 103 cells/mm(2), which corresponds to 10-fold the confluent concentration against the culture area [4 mm(2)]) were seeded into an ultra-low-attachment plate and a magnet (4000 G) was placed under the well. The magnetically labeled ARPE-19 cells formed an approximately 15-layered cell sheet after a 24 h of culture. When the magnet was removed, the sheets were detached from the bottom of the plate and then harvested and transferred to a tissue culture dish, using a magnet. Subsequently, the cell sheets were attached onto the dish, and the cells growing on the sheets were observed. This novel methodology, termed "magnetic force-based tissue engineering" (Mag- TE), is a possible approach for CNV treatment.
C1 Nagoya Univ, Sch Engn, Dept Biotechnol, Chikusa Ku, Nagoya, Aichi 4648603, Japan.
   Nagoya Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 4648603, Japan.
   Nagoya Univ, Sch Med, Dept Tissue Engn, Nagoya, Aichi 466, Japan.
   Nagoya Univ, Sch Med, Dept Oral & Maxillofacial Surg, Nagoya, Aichi 466, Japan.
C3 Nagoya University; Nagoya University; Nagoya University; Nagoya
   University
RP Honda, H (通讯作者)，Nagoya Univ, Sch Engn, Dept Biotechnol, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648603, Japan.
EM honda@nubio.nagoya-u.ac.jp
RI Ito, Akira/S-8099-2017; Terasaki, Hiroko/M-5054-2014
OI Kagami, Hideaki/0000-0003-2285-2602; Ito, Akira/0000-0001-8393-0518
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NR 29
TC 122
Z9 127
U1 0
U2 36
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1076-3279
J9 TISSUE ENG
JI Tissue Eng.
PD MAR
PY 2005
VL 11
IS 3-4
BP 489
EP 496
DI 10.1089/ten.2005.11.489
PG 8
WC Cell & Tissue Engineering
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 924SA
UT WOS:000228999400016
PM 15869427
DA 2022-11-30
ER

PT J
AU Suarez, T
   Biswas, SB
   Biswas, EE
AF Suarez, T
   Biswas, SB
   Biswas, EE
TI Biochemical defects in retina-specific human ATP binding cassette
   transporter nucleotide binding domain 1 mutants associated with macular
   degeneration
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DISEASE GENE ABCR; ARCHAEON THERMOCOCCUS-LITORALIS; STARGARDT-DISEASE;
   FLUORESCENCE ANISOTROPY; MUTATIONAL ANALYSIS; MOLECULAR-GENETICS;
   NUMERICAL-ANALYSIS; ESTROGEN-RECEPTOR; CRYSTAL-STRUCTURE; PIGMENTOSA
AB The retina-specific human ABC transporter (ABCR) functions in the retinal transport system and has been implicated in several inherited visual diseases, including Stargardt disease, fundus flavimaculatus, cone-rod dystrophy, and age-related macular degeneration. We have previously described a general ribonucleotidase activity of the first nucleotide binding domain (NBD1) of human ABCR (Biswas, E. E. (2001) Biochemistry 40, 8181-8187). In this communication, we present a quantitative study analyzing the effects of certain disease-associated mutations, Gly-863 --> Ala, Pro-940 --> Arg, and Arg-943 --> Gln on the nucleotide binding, and general ribonucleotidase activities of this domain. NBD1 proteins, harboring these mutations, were created through in vitro site-specific mutagenesis and expressed in Escherichia coli. Results of the enzyme-kinetic studies indicated that these mutations altered the ATPase and CTPase activities of NBD1. The G863A and P940R mutations were found to have significant attenuation of the rates of nucleotide hydrolysis and binding affinities. On the other hand, the R943Q mutation had small, but detectable reduction in its nucleotidase activity and nucleotide binding affinity. We have measured the nucleotide binding affinities of NB protein and its mutants quantitatively by fluorescence anisotropy changes during protein binding to ethenoadenosine ATP (epsilonATP), a fluorescent ATP analogue. We have correlated the dissociation constant (K-D) and the rates of nucleotide hydrolysis (V-max) of NBD1 and its mutants with the available genetic data for these mutations.
C1 Thomas Jefferson Univ, Dept Lab Sci, Program Biotechnol, Philadelphia, PA 19107 USA.
   Univ Med & Dent New Jersey, Sch Osteopath Med, Dept Mol Biol, Stratford, NJ 08043 USA.
   Univ Med & Dent New Jersey, Grad Sch Biomed Sci, Stratford, NJ 08043 USA.
C3 Jefferson University; Rowan University; Rowan University School of
   Osteopathic Medicine; Rutgers State University New Brunswick; Rutgers
   State University Medical Center; Rutgers State University New Brunswick;
   Rutgers State University Medical Center
RP Biswas, EE (通讯作者)，Thomas Jefferson Univ, Dept Lab Sci, Program Biotechnol, Philadelphia, PA 19107 USA.
FU NATIONAL EYE INSTITUTE [R15EY013113] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM036002] Funding
   Source: NIH RePORTER; NEI NIH HHS [EY13113-01] Funding Source: Medline;
   NIGMS NIH HHS [GM36002-13] Funding Source: Medline
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NR 47
TC 25
Z9 27
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 14
PY 2002
VL 277
IS 24
BP 21759
EP 21767
DI 10.1074/jbc.M202053200
PG 9
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 563YR
UT WOS:000176286000084
PM 11919200
OA hybrid
DA 2022-11-30
ER

PT J
AU Nagaraj, R
   Stack, T
   Yi, SJ
   Mathew, B
   Shull, KR
   Scott, EA
   Mathew, MT
   Bijukumar, DR
AF Nagaraj, Rajini
   Stack, Trevor
   Yi, Sijia
   Mathew, Benjamin
   Shull, Kenneth R.
   Scott, Evan A.
   Mathew, Mathew T.
   Bijukumar, Divya Rani
TI High Density Display of an Anti-Angiogenic Peptide on Micelle Surfaces
   Enhances Their Inhibition of alpha v beta 3 Integrin-Mediated
   Neovascularization In Vitro
SO NANOMATERIALS
LA English
DT Article
DE Micelles; PEG-b-PPS; anti-angiogenic; integrin; VEGF
ID PATHOLOGICAL RETINAL ANGIOGENESIS; ALPHA(V)BETA(3); COMPLICATIONS;
   NANOPARTICLES; ENDOCYTOSIS; ANTAGONIST; MOLECULE; DELIVERY
AB Diabetic retinopathy (DR), Retinopathy of Pre-maturity (ROP), and Age-related Macular Degeneration (AMD) are multifactorial manifestations associated with abnormal growth of blood vessels in the retina. These three diseases account for 5% of the total blindness and vision impairment in the US alone. The current treatment options involve heavily invasive techniques such as frequent intravitreal administration of anti-VEGF (vascular endothelial growth factor) antibodies, which pose serious risks of endophthalmitis, retinal detachment and a multitude of adverse effects stemming from the diverse physiological processes that involve VEGF. To overcome these limitations, this current study utilizes a micellar delivery vehicle (MC) decorated with an anti-angiogenic peptide (aANGP) that inhibits alpha v beta 3 mediated neovascularization using primary endothelial cells (HUVEC). Stable incorporation of the peptide into the micelles (aANGP-MCs) for high valency surface display was achieved with a lipidated peptide construct. After 24 h of treatment, aANGP-MCs showed significantly higher inhibition of proliferation and migration compared to free from aANGP peptide. A tube formation assay clearly demonstrated a dose-dependent angiogenic inhibitory effect of aANGP-MCs with a maximum inhibition at 4 mu g/mL, a 1000-fold lower concentration than that required for free from aANGP to display a biological effect. These results demonstrate valency-dependent enhancement in the therapeutic efficacy of a bioactive peptide following conjugation to nanoparticle surfaces and present a possible treatment alternative to anti-VEGF antibody therapy with decreased side effects and more versatile options for controlled delivery.
C1 [Nagaraj, Rajini; Mathew, Mathew T.; Bijukumar, Divya Rani] Univ Illinois, Coll Med, Dept Biomed Sci, Regenerat Med & Disabil Res Lab, 1601 Parkveiw Ave, Rockford, IL 61107 USA.
   [Stack, Trevor; Yi, Sijia; Shull, Kenneth R.; Scott, Evan A.] Northwestern Univ, Dept Biomed Sci, Evanston, IL 60208 USA.
   [Mathew, Benjamin] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA.
C3 University of Illinois System; University of Illinois Chicago;
   University of Illinois Rockford; Northwestern University; University of
   Illinois System; University of Illinois Chicago; University of Illinois
   Chicago Hospital
RP Bijukumar, DR (通讯作者)，Univ Illinois, Coll Med, Dept Biomed Sci, Regenerat Med & Disabil Res Lab, 1601 Parkveiw Ave, Rockford, IL 61107 USA.
EM rnagar5@uic.edu; trevorstack2019@u.northwestern.edu;
   sijia.yi@northwestern.edu; bmathew3@uic.edu; k-shull@northwestern.edu;
   evan.scott@northwestern.edu; mtmathew@uic.edu; drbiju2@uic.edu
RI Scott, Evan/K-1963-2014; Shull, Kenneth R/B-7536-2009
OI Shull, Kenneth/0000-0002-8027-900X
FU NUANCE
FX The authors acknowledge the support provided by NUANCE, Northwestern
   University for cryo TEM imaging.
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NR 72
TC 7
Z9 7
U1 0
U2 8
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2079-4991
J9 NANOMATERIALS-BASEL
JI Nanomaterials
PD MAR
PY 2020
VL 10
IS 3
AR 581
DI 10.3390/nano10030581
PG 18
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
   Science, Multidisciplinary; Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Science & Technology - Other Topics; Materials Science;
   Physics
GA LD5SO
UT WOS:000526090400181
PM 32235802
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kim, KL
   Seo, S
   Kim, JT
   Kim, J
   Kim, W
   Yeo, Y
   Sung, JH
   Park, SG
   Suh, W
AF Kim, Koung Li
   Seo, Songyi
   Kim, Jee Taek
   Kim, Jaeteak
   Kim, Won
   Yeo, Yeongju
   Sung, Jong-Hyuk
   Park, Sang Gyu
   Suh, Wonhee
TI SCF (Stem Cell Factor) and cKIT Modulate Pathological Ocular
   Neovascularization
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE angiogenesis; catenin; cKIT; endothelial cell; hypoxia; stem cell factor
ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; CHOROIDAL
   NEOVASCULARIZATION; SIGNALING PATHWAY; KIT; EXPRESSION; ANGIOGENESIS;
   ACTIVATION; PHOSPHORYLATION; INACTIVATION
AB Objective: Aberrant neovascularization is a leading cause of blindness in several eye diseases, including age-related macular degeneration and proliferative diabetic retinopathy. The identification of key regulators of pathological ocular neovascularization has been a subject of extensive research and great therapeutic interest. Here, we explored the previously unrecognized role of cKIT and its ligand, SCF (stem cell factor), in the pathological ocular neovascularization process. Approach and Results: Compared with normoxia, hypoxia, a crucial driver of neovascularization, caused cKIT to be highly upregulated in endothelial cells, which significantly enhanced the angiogenic response of endothelial cells to SCF. In murine models of pathological ocular neovascularization, such as oxygen-induced retinopathy and laser-induced choroidal neovascularization models, cKIT and SCF expression was significantly increased in ocular tissues, and blockade of cKIT and SCF using cKit mutant mice and anti-SCF neutralizing IgG substantially suppressed pathological ocular neovascularization. Mechanistically, SCF/cKIT signaling induced neovascularization through phosphorylation of glycogen synthase kinase-3 beta and enhancement of the nuclear translocation of beta-catenin and the transcription of beta-catenin target genes related to angiogenesis. Inhibition of beta-catenin-mediated transcription using chemical inhibitors blocked SCF-induced in vitro angiogenesis in hypoxia, and injection of a beta-catenin agonist into cKit mutant mice with oxygen-induced retinopathy significantly enhanced pathological neovascularization in the retina. Conclusions; Our data reveal that SCF and cKIT are promising novel therapeutic targets for treating vision-threatening ocular neovascular diseases.
C1 [Kim, Koung Li; Seo, Songyi; Yeo, Yeongju; Suh, Wonhee] Chung Ang Univ, Coll Pharm, 84 Heukseok Ro, Seoul 06974, South Korea.
   [Kim, Jee Taek] Chung Ang Univ, Dept Ophthalmol, Seoul, South Korea.
   [Kim, Jaeteak] Chung Ang Univ, Coll Med, Dept Internal Med, Seoul, South Korea.
   [Kim, Won] Chonbuk Natl Univ, Med Sch, Dept Internal Med, Jeonju, South Korea.
   [Sung, Jong-Hyuk] Yonsei Univ, Coll Pharm, Incheon, South Korea.
   [Park, Sang Gyu] Ajou Univ, Coll Pharm, Suwon, South Korea.
C3 Chung Ang University; Chung Ang University; Chung Ang University; Chung
   Ang University Hospital; Jeonbuk National University; Yonsei University;
   Ajou University
RP Suh, W (通讯作者)，Chung Ang Univ, Coll Pharm, 84 Heukseok Ro, Seoul 06974, South Korea.
EM wsuh@cau.ac.kr
FU Bio & Medical Technology Development Program of the National Research
   Foundation - Korea government [2018M3A9H2019045/2018M3A9B5021319]
FX This work was supported by the Bio & Medical Technology Development
   Program of the National Research Foundation funded by the Korea
   government (2018M3A9H2019045/2018M3A9B5021319).
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NR 35
TC 16
Z9 16
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD OCT
PY 2019
VL 39
IS 10
BP 2120
EP 2131
DI 10.1161/ATVBAHA.119.313179
PG 12
WC Hematology; Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Hematology; Cardiovascular System & Cardiology
GA JA2OM
UT WOS:000487656300020
PM 31434494
OA Bronze
DA 2022-11-30
ER

PT J
AU Gasparini, SJ
   Llonch, S
   Borscht, O
   Ader, M
AF Gasparini, Sylvia J.
   Llonch, Silvia
   Borscht, Oliver
   Ader, Marius
TI Transplantation of photoreceptors into the degenerative retina: Current
   state and future perspectives
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Photoreceptor; Transplantation; Pluripotent stem cell; Retinal organoid;
   Retinal degeneration; Functional assessment; Immune privilege
ID PLURIPOTENT STEM-CELLS; LEBER CONGENITAL AMAUROSIS; PIGMENT
   EPITHELIAL-CELLS; HERPES-SIMPLEX-VIRUS; LARGE ANIMAL-MODEL; VESICULAR
   STOMATITIS-VIRUS; RESTORES VISUAL RESPONSES; GENE-THERAPY; PROGENITOR
   CELLS; CONE PHOTORECEPTORS
AB The mammalian retina displays no intrinsic regenerative capacities, therefore retinal degenerative diseases such as age-related macular degeneration (AMD) or retinitis pigmentosa (RP) result in a permanent loss of the light sensing photoreceptor cells. The degeneration of photoreceptors leads to vision impairment and, in later stages, complete blindness. Several therapeutic strategies have been developed to slow down or prevent further retinal degeneration, however a definitive cure i.e. replacement of the lost photoreceptors, has not yet been established. Cell-based treatment approaches, by means of photoreceptor transplantation, have been studied in pre-clinical animal models over the last three decades. The introduction of pluripotent stem cell-derived retinal organoids represents, in principle, an unlimited source for the generation of transplantable human photoreceptors. However, safety, immunological and reproducibility-related issues regarding the use of such cells still need to be solved. Moreover, the recent finding of cytoplasmic material transfer between donor and host photoreceptors demands reinterpretation of several former transplantation studies. At the same time, material transfer between healthy donor and dysfunctional patient photoreceptors also offers a potential alternative strategy for therapeutic intervention. In this review we discuss the history and current state of photoreceptor transplantation, the techniques used to assess rescue of visual function, the prerequisites for effective transplantation as well as the main roadblocks, including safety and immune response to the graft, that need to be overcome for successful clinical translation of photoreceptor transplantation approaches.
C1 [Gasparini, Sylvia J.; Llonch, Silvia; Borscht, Oliver; Ader, Marius] Tech Univ Dresden, CRTD, CMCB, Fetscherstr 105, D-01307 Dresden, Germany.
C3 Technische Universitat Dresden
RP Ader, M (通讯作者)，Tech Univ Dresden, CRTD, CMCB, Fetscherstr 105, D-01307 Dresden, Germany.
EM marius.ader@tu-dresden.de
RI Ader, Marius/E-7535-2010
OI Ader, Marius/0000-0001-9467-7677; Gasparini, Sylvia/0000-0002-3612-6428
FU Deutsche Forschungsgemeinschaft (DFG), Center for Regenerative Therapies
   Dresden [FZT 111, EXC 168]; DFG [AD375/6-1]; Bundesministerium fur
   Bildung and Forschung (BMBF) [01EK1613A]; ProRetina Stiftung,
   Pro-Re/Prom-stip/Ader-Llonch.1-2016
FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG) FZT
   111, Center for Regenerative Therapies Dresden, EXC 168 Cluster of
   Excellence (M.A.), DFG Grant AD375/6-1 (M.A.), Bundesministerium fur
   Bildung and Forschung (BMBF) Research Grant 01EK1613A (M.A.), and the
   ProRetina Stiftung, Pro-Re/Prom-stip/Ader-Llonch.1-2016 (S.L.).
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NR 291
TC 81
Z9 84
U1 4
U2 30
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 2019
VL 69
BP 1
EP 37
DI 10.1016/j.preteyeres.2018.11.001
PG 37
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HW1OL
UT WOS:000466452100001
PM 30445193
OA hybrid
DA 2022-11-30
ER

PT J
AU Trang, N
   Lalonde, G
   Dube, Y
   Bourgault, S
   Rochette, PJ
AF Trang, Nataly
   Lalonde, Gilles
   Dube, Yolande
   Bourgault, Serge
   Rochette, Patrick J.
TI Short wavelengths filtering properties of sunglasses on the Canadian
   market: are we protected?
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
ID ULTRAVIOLET-LIGHT EXPOSURE; AGE-RELATED MACULOPATHY; BEAVER DAM EYE;
   MACULAR DEGENERATION; EPITHELIAL-CELLS; UVEAL MELANOMA; LENS OPACITIES;
   RISK-FACTORS; SUNLIGHT; LIPOFUSCIN
AB Background: Exposure to solar radiation is a risk factor for multiple ocular pathologies. Ultraviolet (UV) radiation is involved in ocular diseases, including pterygium, ocular surface squamous neoplasia, and cataracts. High-energy visible light (HEV) is associated with age-related macular degeneration. Ocular protection against solar radiation seems essential to protect our eyes against the adverse effects of those harmful rays. Australia, New Zealand, Europe, and the United States are the only regions with mandatory standards for UV transmission for sunglasses. Adherence to Canadian standards by sunglasses manufacturers is not mandatory. In this study, we evaluated the UV and visible transmission of sunglasses in the Canadian market to test their compliance with Canadian standards.
   Methods: The transmittance of 207 pairs of sunglasses, divided in 3 categories according to their price range, was measured.
   Results: We show that close to 100% of the sunglasses tested respect the Canadian standards. The average HEV transmittance is around 10%, regardless the price range.
   Conclusions: Our study demonstrated that even if following Canadian standards is optional, most sunglasses sold on the Canadian market follow national and international standards. We also found that sunglasses filter around 90% of HEV. With the recent findings on the potential effects of HEV in retinal pathologies, we can ask whether this filtering capacity is sufficient to protect eyes from harmful HEV light. More work needs to be done to determine acceptable HEV light transmission limits to the existing Canadian standards.
C1 [Trang, Nataly; Lalonde, Gilles; Dube, Yolande; Bourgault, Serge; Rochette, Patrick J.] Univ Laval, Fac Med, Dept Ophtalmol & ORL CCF, Quebec City, PQ, Canada.
   [Trang, Nataly; Lalonde, Gilles; Dube, Yolande; Bourgault, Serge; Rochette, Patrick J.] CHU Quebec, Hop St Sacrement, Ctr Univ Ophtalmol, Quebec City, PQ, Canada.
   [Trang, Nataly; Rochette, Patrick J.] Univ Laval, CHU Quebec, Hop St Sacrement, Ctr Rech,Axe Med Regeneratrice, Quebec City, PQ, Canada.
   [Rochette, Patrick J.] Univ Laval, LOEX, Ctr Rech Organogenese Expt, Quebec City, PQ, Canada.
C3 Laval University; Laval University; Laval University; Laval University
RP Rochette, PJ (通讯作者)，Univ Laval, CHU Quebec, Hop St Sacrement, Ctr Rech, 1050 Chemin Ste Foy, Quebec City, PQ G1S 4L8, Canada.
EM patrick.rochette@orlo.ulaval.ca
RI Bourgault, Serge/ABC-2569-2021
OI Rochette, Patrick/0000-0002-0678-8869
FU Canadian Institutes of Health Research (CIHR); Fonds de Recherche du
   Quebec - Sante (FRQ-S)
FX This work was supported by a grant from the Canadian Institutes of
   Health Research (CIHR) to P.J.R. and to department source. P.J.R is a
   research scholar from the Fonds de Recherche du Quebec - Sante (FRQ-S).
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NR 42
TC 2
Z9 2
U1 0
U2 4
PU CANADIAN OPHTHAL SOC
PI OTTAWA
PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA
SN 0008-4182
EI 1715-3360
J9 CAN J OPHTHALMOL
JI Can. J. Opthalmol.-J. Can. Opthalmol.
PD APR
PY 2018
VL 53
IS 2
BP 104
EP 109
DI 10.1016/j.jcjo.2017.09.006
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GC2NH
UT WOS:000429619200021
PM 29631819
DA 2022-11-30
ER

PT J
AU Zhang, P
   Zhu, M
   Geng-Spyropoulos, M
   Shardell, M
   Gonzalez-Freire, M
   Gudnason, V
   Eiriksdottir, G
   Schaumberg, D
   Van Eyk, JE
   Ferrucci, L
   Semba, RD
AF Zhang, Pingbo
   Zhu, Min
   Geng-Spyropoulos, Minghui
   Shardell, Michelle
   Gonzalez-Freire, Marta
   Gudnason, Vilmundur
   Eiriksdottir, Gudny
   Schaumberg, Debra
   Van Eyk, Jennifer E.
   Ferrucci, Luigi
   Semba, Richard D.
TI A novel, multiplexed targeted mass spectrometry assay for quantification
   of complement factor H (CFH) variants and CFH-related proteins 1-5 in
   human plasma
SO PROTEOMICS
LA English
DT Article
DE Age-related macular degeneration; Biomedicine; Complement factor H;
   Complement factor H-related proteins; Mass spectrometry; Selected
   reaction monitoring
ID C-REACTIVE-PROTEIN; MACULAR DEGENERATION; REGULATORY PROTEINS; BRUCHS
   MEMBRANE; AGE; RISK; POLYMORPHISM; HAPLOTYPES; BINDING; SHOWS
AB Age-related macular degeneration (AMD) is a leading cause of visual loss among older adults. Two variants in the complement factor H (CFH) gene, Y402H and I62V, are strongly associated with risk of AMD. CFH is encoded in regulator of complement activation gene cluster in chromosome 1q32, which includes complement factor related (CFHR) proteins, CFHR1 to CFHR5, with high amino acid sequence homology to CFH. Our goal was to build a SRM assay to measure plasma concentrations of CFH variants Y402, H402, I62, and V62, and CFHR1-5. The final assay consisted of 24 peptides and 72 interference-free SRM transition ion pairs. Most peptides showed good linearity over 0.3-200 fmol/mu L concentration range. Plasma concentrations of CFH variants and CFHR1-5 were measured using the SRM assay in 344 adults. Plasma CFH concentrations (mean, SE in mu g/mL) by inferred genotype were: YY402, II62 (170.1, 31.4), YY402, VV62 (188.8, 38.5), HH402, VV62 (144.0, 37.0), HY402, VV62 (164.2, 42.3), YY402, IV62 (194.8, 36.8), HY402, IV62 (181.3, 44.7). Mean (SE) plasma concentrations of CFHR1-5 were 1.63 (0.04), 3.64 (1.20), 0.020 (0.001), 2.42 (0.18), and 5.49 (1.55) mu g/mL, respectively. This SRM assay should facilitate the study of the role of systemic complement and risk of AMD.
C1 [Zhang, Pingbo; Geng-Spyropoulos, Minghui; Semba, Richard D.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Smith Building M015,400 N Broadway, Baltimore, MD 21287 USA.
   [Zhu, Min; Shardell, Michelle; Gonzalez-Freire, Marta; Ferrucci, Luigi] Natl Inst Hlth, Natl Inst Aging, Baltimore, MD USA.
   [Gudnason, Vilmundur; Eiriksdottir, Gudny] Iceland Heart Assoc, Reykjavik, Iceland.
   [Gudnason, Vilmundur] Univ Iceland, Dept Med, Reykjavik, Iceland.
   [Schaumberg, Debra] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
   [Schaumberg, Debra] Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA.
   [Van Eyk, Jennifer E.] Inst Heart, Adv Clin BioSystems Res Inst, Los Angeles, CA USA.
   [Van Eyk, Jennifer E.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; National Institutes of
   Health (NIH) - USA; NIH National Institute on Aging (NIA); Icelandic
   Heart Association; University of Iceland; Harvard University; Harvard
   T.H. Chan School of Public Health; Utah System of Higher Education;
   University of Utah; Cedars Sinai Medical Center
RP Semba, RD (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Smith Building M015,400 N Broadway, Baltimore, MD 21287 USA.
EM rdsemba@jhmi.edu
RI Gudnason, Vilmundur/AAE-7126-2019; Gonzalez-Freire, Marta/ABG-1197-2020
OI Gudnason, Vilmundur/0000-0001-5696-0084; Gonzalez-Freire,
   Marta/0000-0001-9741-2826
FU National Institutes of Health [R01 EY024596, R01 AG027012, R56 AG052973,
   HHSN271201200022C, N01-AG-12100]; Intramural Research Program of the
   National Institute on Aging; Joint King Khaled Eye Specialist Hospital
   and Wilmer Eye Institute Research Grant Program; Edward N. & Della L.
   Thome Memorial Foundation; Research to Prevent Blindness; National
   Institute on Aging Intramural Research Program; Hjartavernd (the
   Icelandic Heart Association); Althingi (the Icelandic Parliament);
   NATIONAL EYE INSTITUTE [R01EY024596] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE ON AGING [N01AG012100, R56AG052973, R56AG027012,
   R01AG027012] Funding Source: NIH RePORTER
FX This work was supported by the National Institutes of Health grants R01
   EY024596, R01 AG027012, R56 AG052973, the Intramural Research Program of
   the National Institute on Aging, the Joint King Khaled Eye Specialist
   Hospital and Wilmer Eye Institute Research Grant Program, the Edward N.
   & Della L. Thome Memorial Foundation, and Research to Prevent Blindness.
   The AGES Reykjavik study was supported by National Institutes of Health
   (contract nos. N01-AG-12100 and HHSN271201200022C); the National
   Institute on Aging Intramural Research Program; Hjartavernd (the
   Icelandic Heart Association); the Althingi (the Icelandic Parliament).
   [Corrections were made to this article on 21 November 2016, after
   acceptance: in Table 1, Figures 2 and 3 and Results, paragraphs 2 and
   6.]
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NR 40
TC 13
Z9 13
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1615-9853
EI 1615-9861
J9 PROTEOMICS
JI Proteomics
PD MAR
PY 2017
VL 17
IS 6
SI SI
AR 1600237
DI 10.1002/pmic.201600237
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA EP5AV
UT WOS:000397392300008
PM 27647805
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Sundermeier, TR
   Sakami, S
   Sahu, B
   Howell, SJ
   Gao, SQ
   Dong, ZQ
   Golczak, M
   Maeda, A
   Palczewski, K
AF Sundermeier, Thomas R.
   Sakami, Sanae
   Sahu, Bhubanananda
   Howell, Scott J.
   Gao, Songqi
   Dong, Zhiqian
   Golczak, Marcin
   Maeda, Akiko
   Palczewski, Krzysztof
TI MicroRNA-processing Enzymes Are Essential for Survival and Function of
   Mature Retinal Pigmented Epithelial Cells in Mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE eye; retina; retinal degeneration; retinal metabolism; vision; ret;
   retina; retina metabolism
ID MACULAR DEGENERATION; NLRP3 INFLAMMASOME; ALU RNA; TRANSCRIPTION FACTOR;
   GENE-EXPRESSION; MOUSE MODEL; C-ELEGANS; MIRNAS; ROD; PHOTORECEPTORS
AB Age-related macular degeneration (AMD) is a major cause of irreversible vision loss. The neovascular or wet form of AMD can be treated to varying degrees with anti-angiogenic drugs, but geographic atrophy (GA) is an advanced stage of the more prevalent dry form of AMD for which there is no effective treatment. Development of GA has been linked to loss of the microRNA (miRNA)-processing enzyme DICER1 in the mature retinal pigmented epithelium (RPE). This loss results in the accumulation of toxic transcripts of Alu transposable elements, which activate the NLRP3 inflammasome and additional downstream pathways that compromise the integrity and function of the RPE. However, it remains unclear whether the loss of miRNA processing and subsequent gene regulation in the RPE due to DICER1 deficiency also contributes to RPE cell death. To clarify the role of miRNAs in RPE cells, we used two different mature RPE cell-specific Cre recombinase drivers to inactivate either Dicer1 or DiGeorge syndrome critical region 8 (Dgcr8), thus removing RPE miRNA regulatory activity in mice by disrupting two independent and essential steps of miRNA biogenesis. In contrast with prior studies, we found that the loss of each factor independently led to strikingly similar defects in the survival and function of the RPE and retina. These results suggest that the loss of miRNAs also contributes to RPE cell death and loss of visual function and could affect the pathology of dry AMD.
C1 [Sundermeier, Thomas R.; Sakami, Sanae; Gao, Songqi; Golczak, Marcin; Palczewski, Krzysztof] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA.
   [Sahu, Bhubanananda; Howell, Scott J.; Maeda, Akiko] Case Western Reserve Univ, Sch Med, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
   [Golczak, Marcin; Palczewski, Krzysztof] Case Western Reserve Univ, Cleveland Ctr Membrane & Struct Biol, Cleveland, OH 44106 USA.
   [Dong, Zhiqian] Polgenix Inc, Cleveland, OH 44106 USA.
C3 Case Western Reserve University; Case Western Reserve University; Case
   Western Reserve University
RP Palczewski, K (通讯作者)，Case Western Reserve Univ, Sch Med, Cleveland Ctr Membrane & Struct Biol, Dept Pharmacol, 10900 Euclid Ave, Cleveland, OH 44106 USA.
EM kxp65@case.edu
OI Imanishi, Sanae/0000-0001-9884-2123; DONG, ZHIQIAN/0000-0002-8748-4532
FU National Institutes of Health [EY022326, EY R24024864, EY022658,
   EY023948, P30EY011373]; Arnold and Mabel Beckman Foundation; Foundation
   Fighting Blindness; NATIONAL EYE INSTITUTE [R01EY023948, P30EY011373,
   R01EY022658, R01EY022326] Funding Source: NIH RePORTER
FX This research was supported in part by National Institutes of Health
   Grants EY022326 and EY R24024864 (to K.P.), EY022658 (to A. M.),
   EY023948 (to M. G.), and P30EY011373 (from the VSRC CORE grant). This
   work was also supported by the Arnold and Mabel Beckman Foundation and
   the Foundation Fighting Blindness. The authors declare that they have no
   conflicts of interest with the contents of this article. 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 56
TC 20
Z9 22
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 24
PY 2017
VL 292
IS 8
BP 3366
EP 3378
DI 10.1074/jbc.M116.770024
PG 13
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA EM8CM
UT WOS:000395538800026
PM 28104803
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Lai, PX
   Chen, CW
   Wei, SC
   Lin, TY
   Jian, HJ
   Lai, IPJ
   Mao, JY
   Hsu, PH
   Lin, HJ
   Tzou, WS
   Chen, SY
   Harroun, SG
   Lai, JY
   Huang, CC
AF Lai, Pei-Xin
   Chen, Chung-Wein
   Wei, Shih-Chun
   Lin, Tzu-Yu
   Jian, Hong-Jyuan
   Lai, Irving Po-Jung
   Mao, Ju-Yi
   Hsu, Pang-Hung
   Lin, Han-Jia
   Tzou, Wen-Shyong
   Chen, Shiow-Yi
   Harroun, Scott G.
   Lai, Jui-Yang
   Huang, Chih-Ching
TI Ultrastrong trapping of VEGF by graphene oxide: Anti-angiogenesis
   application
SO BIOMATERIALS
LA English
DT Article
DE Anti-angiogenesis; Graphene oxide; Vascular endothelial growth factor;
   Serum albumin; Blood vessel; Corneal neovascularization
ID ENDOTHELIAL GROWTH-FACTOR; CORNEAL NEOVASCULARIZATION; TUMOR
   ANGIOGENESIS; CRITICAL REGULATOR; CELL MIGRATION; IN-VITRO;
   NANOPARTICLES; DELIVERY; BINDING; SERUM
AB Angiogenesis is the process of formation of new blood vessels, which is essential to human biology, and also plays a crucial role in several pathologies such as tumor growth and metastasis, exudative age related macular degeneration, and ischemia. Vascular endothelial growth factor (VEGF), in particular, VEGF-A(165) is the most important pro-angiogenic factor for angiogenesis. Thus, blocking the interaction between VEGFs and their receptors is considered an effective anti-angiogenic strategy. We demonstrate for that first time that bovine serum albumin-capped graphene oxide (BSA-GO) exhibits high stability in physiological saline solution and possesses ultrastrong binding affinity towards VEGF-A(165) [dissociation constant (K-d) similar to 3 x 10(-12) M], which is at least five orders of magnitude stronger than that of high abundant plasma proteins such as human serum albumin, fibrinogen, transferrin, and immunoglobulin G. Due to the surprising binding specificity of BSA GO for VEGF-A(165) in complex plasma fluid, we have also studied the anti-angiogenic effects in vitro and in vivo. Results show that BSA GO not only effectively inhibits the proliferation, migration and tube formation of human umbilical vein endothelial cells, but also strongly disturbs the physiological process of angiogenesis in chick chorioallantoic membrane and blocks VEGF-A(165)-induced blood vessel formation in rabbit corneal neovascularization. Our findings indicate that GO nanomaterials can potentially act as therapeutic anti-angiogenic agents via ultrastrong VEGF adsorption and its activity suppression. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Lai, Pei-Xin; Chen, Chung-Wein; Wei, Shih-Chun; Lai, Irving Po-Jung; Mao, Ju-Yi; Hsu, Pang-Hung; Lin, Han-Jia; Tzou, Wen-Shyong; Chen, Shiow-Yi; Huang, Chih-Ching] Natl Taiwan Ocean Univ, Dept Biosci & Biotechnol, 2 Pei Ning Rd, Keelung 20224, Taiwan.
   [Lin, Tzu-Yu; Jian, Hong-Jyuan; Lai, Jui-Yang] Chang Gung Univ, Inst Biochem & Biomed Engn, 259 Wen Hwa 1st Rd, Taoyuan 33302, Taiwan.
   [Harroun, Scott G.] Univ Montreal, Dept Chem, Montreal, PQ H3C 3J7, Canada.
   [Lai, Jui-Yang] Chang Gung Mem Hosp, Dept Ophthalmol, Taoyuan 33305, Taiwan.
   [Lai, Jui-Yang] Chang Gung Mem Hosp, Ctr Tissue Engn, Taoyuan 33305, Taiwan.
   [Huang, Chih-Ching] Natl Taiwan Ocean Univ, Ctr Excellence Oceans, Keelung 20224, Taiwan.
   [Huang, Chih-Ching] Kaohsiung Med Univ, Coll Pharm, Sch Pharm, Kaohsiung 80708, Taiwan.
C3 National Taiwan Ocean University; Chang Gung University; Universite de
   Montreal; Chang Gung Memorial Hospital; Chang Gung Memorial Hospital;
   National Taiwan Ocean University; Kaohsiung Medical University
RP Huang, CC (通讯作者)，Natl Taiwan Ocean Univ, Dept Biosci & Biotechnol, 2 Pei Ning Rd, Keelung 20224, Taiwan.; Lai, JY (通讯作者)，Chang Gung Univ, Inst Biochem & Biomed Engn, 259 Wen Hwa 1st Rd, Taoyuan 33302, Taiwan.
EM jylai@mail.cgu.edu.tw; huanging@ntou.edu.tw
RI Tzou, Wen-Shyong/H-4517-2014; Huang, Chih-Ching/D-3103-2012; Lai,
   Jui-Yang/I-1166-2017; Hsu, Pang-Hung/C-5587-2018; Harroun, Scott
   G./ABG-3694-2021
OI Tzou, Wen-Shyong/0000-0002-6726-1390; Huang,
   Chih-Ching/0000-0002-0363-1129; Lai, Jui-Yang/0000-0002-9227-8549; Hsu,
   Pang-Hung/0000-0001-6873-6434; Mao, Ju-Yi/0000-0002-3008-5717; Harroun,
   Scott/0000-0003-3370-5341; Lin, Han-Jia/0000-0002-4929-6573; Wei,
   Shih-Chun/0000-0002-3771-3069
FU Ministry of Science and Technology of Taiwan [104-2628-M-019-001-MY3,
   103-2314-B-182-013, 103-2627-M-007-002-MY3]; Chang Gung Memorial
   Hospital [CMRPD3D0101]
FX This study was supported by the Ministry of Science and Technology of
   Taiwan under Contract Nos. 104-2628-M-019-001-MY3, 103-2314-B-182-013,
   and 103-2627-M-007-002-MY3 and by Chang Gung Memorial Hospital under
   Contract No. CMRPD3D0101.
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NR 69
TC 42
Z9 50
U1 2
U2 103
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 DEC
PY 2016
VL 109
BP 12
EP 22
DI 10.1016/j.biomaterials.2016.09.005
PG 11
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA EA2FF
UT WOS:000386407500002
PM 27639528
DA 2022-11-30
ER

PT J
AU Doyle, SL
   Lopez, FJ
   Celkova, L
   Brennan, K
   Ozaki, E
   Mulfaul, K
   Kenna, PF
   Kurali, E
   Hudson, N
   Doggett, T
   Ferguson, TA
   Humphries, P
   Adamson, P
   Campbell, M
AF Doyle, Sarah L.
   Lopez, Francisco J.
   Celkova, Lucia
   Brennan, Kiva
   Ozaki, Ema
   Mulfaul, Kelly
   Kenna, Paul F.
   Kurali, Edit
   Hudson, Natalie
   Doggett, Teresa
   Ferguson, Thomas A.
   Humphries, Peter
   Adamson, Peter
   Campbell, Matthew
TI IL-18 Immunotherapy for Neovascular AMD: Tolerability and Efficacy in
   Nonhuman Primates
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE interleukin-18; immunotherapy; age-related macular degeneration
ID CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; INTERLEUKIN-18;
   VEGF; ANGIOGENESIS; THERAPY; MOUSE
AB PURPOSE. Age-related macular degeneration is the most common form of central retinal blindness in the elderly. Of the two end stages of disease, neovascular AMD-although theminority formis the most severe. Current therapies are highly successful at controlling progression of neovascular lesions; however, a significant number of patients remain refractory to treatment and the development of alternative and additive therapies to anti-VEGFs is essential.
   METHODS. In order to address the translational potential of interleukin (IL)-18 for use in neovascular AMD, we initiated a nonhuman primate tolerability and efficacy study for the use of intravitreally (IVT) administered clinical grade human IL-18 (SB-485232). Cynomolgus monkeys were injected IVT with increasing doses of human IL-18 (two each at 1000, 3000, and 10,000 ng per eye). In tandem, 21 monkeys were administered nine laser burns in each eye prior to receiving IL-18 as an IVT injection at a range of doses. Fundus fluorescein angiography (FFA) was performed on days 8, 15, and 22 post injection and the development of neovascular lesions was assessed.
   RESULTS. We show intravitreal, mature, recombinant human IL-18 is safe and can reduce choroidal neovascular lesion development in cynomolgus monkeys.
   CONCLUSIONS. Based on our data comparing human IL-18 to current anti-VEGF-based therapy, clinical deployment of IL-18 for neovascular AMD has the potential to lead to a new adjuvant immunotherapy-based treatment for this severe form of central blindness.
C1 [Doyle, Sarah L.; Brennan, Kiva; Ozaki, Ema] Trinity Coll Dublin, Sch Med, Dept Clin Med, Dublin 2, Ireland.
   [Lopez, Francisco J.] GlaxoSmithKline, Ophthalmol Discovery Performance Unit, King Of Prussia, PA USA.
   [Celkova, Lucia; Ozaki, Ema; Mulfaul, Kelly; Hudson, Natalie; Humphries, Peter; Campbell, Matthew] Trinity Coll Dublin, Smurfit Inst Genet, Ocular Genet Unit, Dublin 2, Ireland.
   [Kenna, Paul F.] Royal Victoria Eye & Ear Hosp, Res Fdn, Dublin, Ireland.
   [Kurali, Edit] GlaxoSmithKline, PTS, Stat Consulting Grp, Quantitat Sci, King Of Prussia, PA USA.
   [Doggett, Teresa; Ferguson, Thomas A.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
   [Adamson, Peter] GlaxoSmithKline, Ophthalmol Discovery Performance Unit, Stevenage, Herts, England.
   [Adamson, Peter] UCL, Inst Ophthalmol, Ocular Biol & Therapeut, London, England.
C3 Trinity College Dublin; GlaxoSmithKline; Trinity College Dublin;
   GlaxoSmithKline; Washington University (WUSTL); GlaxoSmithKline;
   University of London; University College London
RP Doyle, SL (通讯作者)，Trinity Coll Dublin, Sch Med, Dept Clin Med, Dublin 2, Ireland.
EM sarah.doyle@tcd.ie; matthew.campbell@tcd.ie
OI Brennan, Kiva/0000-0003-4960-7076; Doyle, Sarah/0000-0002-6294-9380;
   Mulfaul, Kelly/0000-0003-4441-4806
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NR 18
TC 27
Z9 29
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 2015
VL 56
IS 9
BP 5424
EP 5430
DI 10.1167/iovs.15-17264
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CT5WW
UT WOS:000362882800050
PM 26284546
DA 2022-11-30
ER

PT J
AU Cuenca, N
   Fernandez-Sanchez, L
   Campello, L
   Maneu, V
   De la Villa, P
   Lax, P
   Pinilla, I
AF Cuenca, Nicolas
   Fernandez-Sanchez, Laura
   Campello, Laura
   Maneu, Victoria
   De la Villa, Pedro
   Lax, Pedro
   Pinilla, Isabel
TI Cellular responses following retinal injuries and therapeutic approaches
   for neurodegenerative diseases
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE Retinal remodeling; Neurodegeneration; Glial cells; Retinal therapy;
   Neuroprotection; Retinal diseases
ID ENDOTHELIAL GROWTH-FACTOR; EMBRYONIC STEM-CELLS; PIGMENT
   EPITHELIAL-CELLS; ENDOPLASMIC-RETICULUM STRESS; CENTRAL-NERVOUS-SYSTEM;
   INDUCED PHOTORECEPTOR DEGENERATION; PHOTOPIC NEGATIVE RESPONSE;
   INTRAOCULAR GENE-TRANSFER; RESTORES VISUAL RESPONSES; FIBRILLARY ACIDIC
   PROTEIN
AB Retinal neurodegenerative diseases like age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa each have a different etiology and pathogenesis. However, at the cellular and molecular level, the response to retinal injury is similar in all of them, and results in morphological and functional impairment of retinal cells. This retinal degeneration may be triggered by gene defects, increased intraocular pressure, high levels of blood glucose, other types of stress or aging, but they all frequently induce a set of cell signals that lead to well-established and similar morphological and functional changes, including controlled cell death and retinal remodeling. Interestingly, an inflammatory response, oxidative stress and activation of apoptotic pathways are common features in all these diseases. Furthermore, it is important to note the relevant role of glial cells, including astrocytes, Muller cells and microglia, because their response to injury is decisive for maintaining the health of the retina or its degeneration. Several therapeutic approaches have been developed to preserve retinal function or restore eyesight in pathological conditions. In this context, neuroprotective compounds, gene therapy, cell transplantation or artificial devices should be applied at the appropriate stage of retinal degeneration to obtain successful results. This review provides an overview of the common and distinctive features of retinal neurodegenerative diseases, including the molecular, anatomical and functional changes caused by the cellular response to damage, in order to establish appropriate treatments for these pathologies. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Cuenca, Nicolas; Fernandez-Sanchez, Laura; Campello, Laura; Lax, Pedro] Univ Alicante, Dept Physiol Genet & Microbiol, E-03080 Alicante, Spain.
   [Cuenca, Nicolas] Univ Alicante, Multidisciplinary Inst Environm Studies Ramon Mar, E-03080 Alicante, Spain.
   [Maneu, Victoria] Univ Alicante, Dept Opt Pharmacol & Anat, E-03080 Alicante, Spain.
   [De la Villa, Pedro] Univ Alcala, Dept Syst Biol, Alcala De Henares, Spain.
   [Pinilla, Isabel] Lozano Blesa Univ Hosp, Aragon Inst Hlth Sci, Dept Ophthalmol, Zaragoza, Spain.
C3 Universitat d'Alacant; Universitat d'Alacant; Universitat d'Alacant;
   Universidad de Alcala; Lozano Blesa University Clinical Hospital
RP Cuenca, N (通讯作者)，Univ Alicante, Dept Physiol Genet & Microbiol, E-03080 Alicante, Spain.
EM cuenca@ua.es
RI Cuenca, Nicolas/I-2007-2015; de la Villa, Pedro/G-2322-2016; Maneu,
   Victoria/N-4147-2014; Fernandez-Sanchez, Laura/AAB-5663-2019; Lax,
   Pedro/M-9074-2014
OI Cuenca, Nicolas/0000-0002-6767-5710; de la Villa,
   Pedro/0000-0001-9856-6616; Maneu, Victoria/0000-0002-5265-1361;
   Fernandez-Sanchez, Laura/0000-0002-3629-0156; Lax,
   Pedro/0000-0001-6931-1008; Pinilla, Isabel/0000-0003-0349-9997;
   Campello, Laura/0000-0002-0869-1315
FU Spanish Ministry of Economy and Competitiveness-FEDER [BFU2012-36845];
   Plan Nacional de I+D+I; Instituto de Salud Carlos III; Subdireccion
   General de Redes y Centros de Investigacion Cooperativa [RETICS
   RD07/0062/0008-0012, RETICS RD12/0034/0006-0010, PS0901854, PI13/01124];
   ONCE; FUNDALUCE
FX This work was supported by project grants from the Spanish Ministry of
   Economy and Competitiveness-FEDER (BFU2012-36845), Plan Nacional de
   I+D+I 2008-2011, Instituto de Salud Carlos III, Subdireccion General de
   Redes y Centros de Investigacion Cooperativa (RETICS
   RD07/0062/0008-0012, RETICS RD12/0034/0006-0010, PS0901854, PI13/01124),
   ONCE and FUNDALUCE.
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NR 703
TC 259
Z9 269
U1 5
U2 140
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 NOV
PY 2014
VL 43
BP 17
EP 75
DI 10.1016/j.preteyeres.2014.07.001
PG 59
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AS7NH
UT WOS:000344442100002
PM 25038518
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Told, R
   Palkovits, S
   Boltz, A
   Schmidl, D
   Napora, KJ
   Werkmeister, RM
   Haslacher, H
   Frantal, S
   Popa-Cherecheanu, A
   Schmetterer, L
   Garhofer, G
AF Told, Reinhard
   Palkovits, Stefan
   Boltz, Agnes
   Schmidl, Doreen
   Napora, Katarzyna J.
   Werkmeister, Rene M.
   Haslacher, Helmuth
   Frantal, Sophie
   Popa-Cherecheanu, Alina
   Schmetterer, Leopold
   Garhoefer, Gerhard
TI Flicker-induced retinal vasodilatation is not dependent on complement
   factor H polymorphism in healthy young subjects
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE dynamic vessel analyzer; eye; flicker light stimulation; retinal
   circulation; Retinal vessel diameter; rs1061170; vasodilation; Y402H
   polymorphism; young healthy subjects
ID OCULAR BLOOD-FLOW; DIFFUSE LUMINANCE FLICKER; C-REACTIVE PROTEIN;
   OPTIC-NERVE HEAD; MACULAR DEGENERATION; VESSEL DIAMETERS; CHOROIDAL
   NEOVASCULARIZATION; MYOCARDIAL-INFARCTION; AGE; RISK
AB PurposeThe complement factor H (CFH) tyrosine 402 histidine (Y402H, rs1061170) variant is known to be significantly associated with age-related macular degeneration (AMD). Whether this genetic variant may impact retinal blood flow regulation is largely unknown. This study investigated whether flicker-induced vasodilation, an indicator for the coupling between neural activity and blood flow, is altered in subjects carrying the rs1061170 risk allele.
   MethodsOne hundred healthy subjects (aged between 18 and 45years) were included in this study. Retinal blood flow regulation was tested by assessing retinal vessel calibres in response to stimulation with diffuse flicker light. Retinal vascular flicker responses were determined with a Dynamic Vessel Analyzer (DVA). In addition, genotyping for rs1061170 was performed.
   ResultsEighteen subjects were homozygous for the risk allele C, 50 were homozygous for the ancestral allele T, and 31 subjects were heterozygous (CT). One subject had to be excluded from data evaluation, as no genetic analysis could be performed due to technical difficulties. Baseline diameters of retinal arteries (p=0.39) and veins (p=0.64) were comparable between the three groups. Flicker-induced vasodilation in both retinal arteries (p=0.38) and retinal veins (p=0.62) was also comparable between the three studied groups.
   ConclusionsOur data indicate that homozygous healthy young carriers of the C risk allele at rs1061170 do not show abnormal flicker-induced vasodilation in the retina. This suggests that the high-risk genetic variant of CFH polymorphism does not impact neuro-vascular coupling in healthy subjects.
C1 [Told, Reinhard; Palkovits, Stefan; Boltz, Agnes; Schmidl, Doreen; Napora, Katarzyna J.; Schmetterer, Leopold; Garhoefer, Gerhard] Med Univ Vienna, Dept Clin Pharmacol, A-1090 Vienna, Austria.
   [Told, Reinhard; Boltz, Agnes; Napora, Katarzyna J.; Werkmeister, Rene M.; Schmetterer, Leopold] Med Univ Vienna, Ctr Med Phys & Biomed Engn, A-1090 Vienna, Austria.
   [Haslacher, Helmuth] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria.
   [Frantal, Sophie] Med Univ Vienna, Ctr Med Stat Informat & Intelligence Syst, A-1090 Vienna, Austria.
   [Popa-Cherecheanu, Alina] Emergency Univ Hosp, Dept Ophthalmol, Bucharest, Romania.
C3 Medical University of Vienna; Medical University of Vienna; Medical
   University of Vienna; Medical University of Vienna
RP Garhofer, G (通讯作者)，Med Univ Vienna, Dept Clin Pharmacol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM gerhard.garhoefer@meduniwien.ac.at
RI H, Haslacher/D-4233-2013
OI H, Haslacher/0000-0003-4605-2503; Schmetterer,
   Leopold/0000-0002-7189-1707; Popa-Cherecheanu,
   Alina/0000-0003-4189-6571; Told, Reinhard/0000-0003-2046-7081; Schmidl,
   Doreen/0000-0001-5664-7768
FU Austrian Science Fund (FWF) [P 21406, KLI 250]; Christian Doppler
   Laboratory for Laser Development and their Application in Medicine
FX Financial support of the Austrian Science Fund (FWF, projects P 21406,
   KLI 250) and the Christian Doppler Laboratory for Laser Development and
   their Application in Medicine is gratefully acknowledged.
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NR 54
TC 6
Z9 6
U1 0
U2 14
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 2014
VL 92
IS 7
BP e540
EP e545
DI 10.1111/aos.12433
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AS3FN
UT WOS:000344162700006
PM 24863099
OA Green Published
DA 2022-11-30
ER

PT J
AU Akuffo, KO
   Beatty, S
   Stack, J
   Dennison, J
   O'Regan, S
   Meagher, KA
   Peto, T
   Nolan, J
AF Akuffo, Kwadwo Owusu
   Beatty, Stephen
   Stack, Jim
   Dennison, Jessica
   O'Regan, Sarah
   Meagher, Katherine A.
   Peto, Tunde
   Nolan, John
TI Central Retinal Enrichment Supplementation Trials (CREST): Design and
   Methodology of the CREST Randomized Controlled Trials
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Age-related macular degeneration; lutein; macular pigment;
   meso-zeaxanthin; randomized clinical trial; visual performance;
   zeaxanthin
ID MACULAR PIGMENT DENSITY; CONTRAST SENSITIVITY; CLINICAL-TRIAL; AGE;
   CAROTENOIDS; RELIABILITY; ZEAXANTHIN; LUTEIN; DEGENERATION; AUGMENTATION
AB Purpose: The Central Retinal Enrichment Supplementation Trials (CREST) aim to investigate the potential impact of macular pigment (MP) enrichment, following supplementation with a formulation containing 10mg lutein (L), 2mg zeaxanthin (Z) and 10mg meso-zeaxanthin (MZ), on visual function in normal subjects (Trial 1) and in subjects with early age-related macular degeneration (AMD; Trial 2).
   Methods: CREST is a single center, double-blind, randomized clinical trial. Trial 1 (12-month follow-up) subjects are randomly assigned to a formulation containing 10mgL, 10mg MZ and 2mg Z (n = 60) or placebo (n = 60). Trial 2 (24-month follow-up) subjects are randomly assigned to a formulation containing 10mgL, 10mg MZ, 2mg Z plus 500mg vitamin C, 400 IU vitamin E, 25mg zinc and 2mg copper (Intervention A; n = 75) or 10mgL and 2mg Z plus 500mg vitamin C, 400 IU vitamin E, 25mg zinc and 2mg copper (Intervention B; n = 75). Contrast sensitivity (CS) at 6 cycles per degree represents the primary outcome measure in each trial. Secondary outcomes include: CS at other spatial frequencies, MP, best-corrected visual acuity, glare disability, photostress recovery, light scatter, cognitive function, foveal architecture, serum carotenoid concentrations, and subjective visual function. For Trial 2, AMD morphology, reading speed and reading acuity are also being recorded.
   Conclusions: CREST is the first study to investigate the impact of supplementation with all three macular carotenoids in the context of a large, double-blind, randomized clinical trial.
C1 [Akuffo, Kwadwo Owusu; Beatty, Stephen; Stack, Jim; Dennison, Jessica; O'Regan, Sarah; Meagher, Katherine A.; Nolan, John] Waterford Inst Technol, Dept Chem & Life Sci, Macular Pigment Res Grp, Carriganore, Waterford, 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); University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   University of London; University College London
RP Akuffo, KO (通讯作者)，Waterford Inst Technol, Vis Res Ctr, Macular Pigment Res Grp, West Campus, Carriganore, Waterford, Ireland.
EM kakuffo@wit.ie
RI Dennison, Jessica/AAG-1199-2020; Akuffo, Kwadwo Owusu/J-2036-2019; Peto,
   Tunde/G-8812-2018; Nolan, John/N-4921-2014
OI Akuffo, Kwadwo Owusu/0000-0001-6683-249X; Peto,
   Tunde/0000-0001-6265-0381; Dennison, Jessica/0000-0001-8793-9237; Nolan,
   John/0000-0002-5503-7084
FU European Research Council (ERC) [281096]
FX This study was funded by the European Research Council (ERC); reference
   number: 281096.
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NR 67
TC 27
Z9 27
U1 1
U2 7
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 2014
VL 21
IS 2
BP 111
EP 123
DI 10.3109/09286586.2014.888085
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AC9RM
UT WOS:000332872000008
PM 24621122
OA hybrid, Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Galetovic, D
   Olujic, I
   Znaor, L
   Bucan, K
   Karlica, D
   Lesin, M
   Susac, T
AF Galetovic, Davor
   Olujic, Ivana
   Znaor, Ljubo
   Bucan, Kajo
   Karlica, Dobrila
   Lesin, Mladen
   Susac, Tihomir
TI THE ROLE OF DIABETIC RETINOPATHY IN BLINDNESS AND POOR SIGHT IN
   SPLIT-DALMATIA COUNTY 2000-2010
SO ACTA CLINICA CROATICA
LA English
DT Article
DE Blindness; Diabetes - complications; Diabetic retinopathy; Incidence;
   Croatia - epidemiology; Split-Dalmatia County
ID AGE
AB Diabetic retinopathy is the fifth leading cause of blindness in the world. The aim of this study was to determine the number of blind persons in the Split-Dalmatia County in the 2000-2010 period and how many of them are blind due to diabetic retinopathy. Records of 160 members of the Association of the Blind in the Split-Dalmatia County, enrolled from 2000 to 2010, were retrospectively analyzed. The leading causes of blindness were diabetic retinopathy (25.6%), glaucoma (13.1%), retinal dystrophy (16.2%), and age related macular degeneration (11.8%). The annual incidence of blindness was 8.4/100,000 inhabitants. The largest number of the blind were found in the 70-80 (21.2%) to >80 (24.3%) age group. Diabetic retinopathy was the cause of blindness in 24 (15%) men and 17 (10.6%) women. The annual incidence of diabetic retinopathy was 2.16 per 100,000. No case of blindness due to diabetic retinopathy was diagnosed in patients younger than 30 years of age, while the highest prevalence was found in the 70-80 age group (34%). Proliferative diabetic retinopathy was the cause of blindness in 92.7% and nonproliferative diabetic retinopathy in 7.3% of cases. Study results show that diabetic retinopathy remains the leading cause of blindness. Early identification of high-risk patients is the key factor in prevention and timely detection of ophthalmoscopic changes, thus enabling effective and duly treatment.
C1 [Galetovic, Davor; Olujic, Ivana; Znaor, Ljubo; Bucan, Kajo; Karlica, Dobrila; Lesin, Mladen; Susac, Tihomir] Split Univ, Dept Clin Ophthalmol, Ctr Hosp, HR-21000 Split, Croatia.
C3 University of Split
RP Galetovic, D (通讯作者)，Split Univ, Dept Clin Ophthalmol, Ctr Hosp, Spinciceva 1, HR-21000 Split, Croatia.
EM davor.galetovic@st.t-com.hr
RI Znaor, Ljubo/H-2445-2017; Bucan, Kajo/H-6144-2017; Karlica Utrobičić,
   Dobrila/H-2288-2017
OI Znaor, Ljubo/0000-0002-0569-0181; Bucan, Kajo/0000-0003-2684-3447; 
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NR 15
TC 5
Z9 5
U1 1
U2 2
PU SESTRE MILOSRDNICE UNIV HOSPITAL
PI ZAGREB
PA VINOGRADSKA C 29, ZAGREB, HR-10000, CROATIA
SN 0353-9466
EI 1333-9451
J9 ACTA CLIN CROAT
JI Acta Clin. Croat.
PD DEC
PY 2013
VL 52
IS 4
BP 448
EP 452
PG 5
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA AC5XI
UT WOS:000332593900005
PM 24696994
DA 2022-11-30
ER

PT J
AU Seo, SJ
   Krebs, MP
   Mao, HY
   Jones, K
   Conners, M
   Lewin, AS
AF Seo, Soo-jung
   Krebs, Mark P.
   Mao, Haoyu
   Jones, Kyle
   Conners, Mandy
   Lewin, Alfred S.
TI Pathological consequences of long-term mitochondrial oxidative stress in
   the mouse retinal pigment epithelium
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retinal pigment epithelium; oxidative stress; superoxide dismutase;
   mitochondria; mouse model; age related macular degeneration
ID SUBRETINAL DRUSENOID DEPOSITS; MACULAR DEGENERATION;
   SUPEROXIDE-DISMUTASE; RETICULAR PSEUDODRUSEN; GEOGRAPHIC ATROPHY;
   CIGARETTE-SMOKING; DAMAGE; MODEL; PREVALENCE; PROTECTION
AB Oxidative stress in the retinal pigment epithelium (RPE) is hypothesized to be a major contributor to the development of age-related macular degeneration (AMD). Mitochondrial manganese superoxide dismutase (MnSOD) is a critical antioxidant protein that scavenges the highly reactive superoxide radical. We speculated that specific reduction of MnSOD in the RPE will increase the level of reactive oxygen species in the retina/RPE/choroid complex leading to pathogenesis similar to geographic atrophy. To test this hypothesis, an Sod2-specific hammerhead ribozyme (Rz), delivered by AAV2/1 and driven by the human VMD2 promoter was injected subretinally into C57BL/6J mice. Dark-adapted full field electroretinogram (ERG) detected a decrease in the response to light. We investigated the age-dependent phenotypic and morphological changes of the outer retina using digital fundus imaging and SD-OCT measurement of ONL thickness. Fundus microscopy revealed pigmentary abnormalities in the retina and these corresponded to sub-retinal and sub-RPE deposits seen in SD-OCT B-scans. Light and electron microscopy documented the localization of apical deposits and thickening of the RPE. In RPE flat-mounts we observed abnormally displaced nuclei and regions of apparent fibrosis in the central retina of the oldest mice. This region was surrounded by enlarged and irregular RPE cells that have been observed in eyes donated by AMD patients and in other mouse models of AMD. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Seo, Soo-jung; Krebs, Mark P.; Mao, Haoyu; Jones, Kyle; Conners, Mandy; Lewin, Alfred S.] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
C3 State University System of Florida; University of Florida
RP Lewin, AS (通讯作者)，Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
EM lewin@ufl.edu
OI Krebs, Mark/0000-0001-9017-6066; Lewin, Alfred/0000-0002-4192-9727
FU Macula Vision Research Foundation; James and Esther King Biomedical
   Research Program [1KG08-33981]; National Eye Institute [5R01EY020825,
   P30-EY021721]; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
   [UL1TR000064] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [P30EY021721, R01EY020825] Funding Source: NIH RePORTER
FX This research was funded by grants from the Macula Vision Research
   Foundation, the James and Esther King Biomedical Research Program
   (1KG08-33981) and the National Eye Institute (5R01EY020825, and
   P30-EY021721).
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NR 48
TC 37
Z9 37
U1 0
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 2012
VL 101
BP 60
EP 71
DI 10.1016/j.exer.2012.05.013
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 984QE
UT WOS:000307205300009
PM 22687918
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Naeem, M
   Khan, A
   Khan, MZU
   Adil, M
   Abbas, SH
   Khan, MU
   Naz, SM
AF Naeem, Mohammad
   Khan, Ayasha
   Khan, Muhammad Zia-ul-Islam
   Adil, Muhammad
   Abbas, Syed Hussain
   Khan, Muhammad Usman
   Naz, Syeda Maria
TI Cataract: trends in surgical procedures and visual outcomes; a study in
   a tertiary care hospital
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Article
DE Cataract procedure; Visual outcome; Cataract complications
ID SURGERY; PREVALENCE
AB Objective: To determine the current procedures in practice and visual outcome following a cataract surgery.
   Methods: The study was conducted from January 7 to April 7, 2011 in the Eye Unit of the Lady Reading Hospital, Peshawar, involving 181 patients. Basic demographics of the patients as well as the type of cataract surgery were noted. Risk factors like diabetes mellitus and glaucoma were also noted for each patient. A pre-operative visual acuity was determined. The patient was examined after two months to determine the visual improvement.
   Results: Out of 181 patients, 117 were males and 64 were females. Age ranged from 5 years to 83 years with a median age of 60. Most common procedure performed (60.2%) was extra capsular cataract extraction with posterior chamber intraocular lense (ECCE), followed by Phacoemulsification (24.3%). Visual outcome was good in 88.3%, borderline in 8.3% and poor in 3.3% patients. The main reasons for poor visual outcomes were diabetic retinopathy 42.8%, glaucoma-related vision loss 19.0%, history of trauma with retinal detachment 9.5%, and age-related macular degeneration 9.5%. Poor visual outcome was found in diabetic and Glaucoma patients. Surgical complications (3.8%) were rare.
   Conclusion: Overall a good visual outcome was noted in cataract surgery, which was similar to World Health Organisation guidelines. Extra capsular cataract extraction was the most common procedure followed by Phacoemulsification.
C1 [Naeem, Mohammad] Khyber Med Coll, Dept Community Med, Peshawar, Pakistan.
   [Khan, Ayasha] Lady Reading Hosp, Peshawar, Pakistan.
   [Khan, Muhammad Usman; Naz, Syeda Maria] Khyber Teaching Hosp, Peshawar, Pakistan.
RP Naeem, M (通讯作者)，Khyber Med Coll, Dept Community Med, Peshawar, Pakistan.
CR Alain M, 2007, PAK J OPHTHALMOL, P2373
   [Anonymous], 2003, Community Eye Health, V16, P49
   [Anonymous], 2011, CAT REM
   Ashaye A O, 2009, West Afr J Med, V28, P102
   Cook C, 2000, Community Eye Health, V13, P37
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   Jadoon Z, 2007, BRIT J OPHTHALMOL, V91, P1269, DOI 10.1136/bjo.2006.106914
   Khan MT, 2010, PAKISTAN J OPHTHALMO, V26, P32
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   Pershing S, 2011, CURR OPIN OPHTHALMOL, V22, P37, DOI 10.1097/ICU.0b013e3283414fb3
   Qureshi MH, 2007, PAK J OPHTHALMOL, V23, P1
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NR 17
TC 5
Z9 6
U1 0
U2 2
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD MAR
PY 2012
VL 62
IS 3
BP 209
EP 212
PG 4
WC Medicine, General & Internal; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Research & Experimental Medicine
GA 892HJ
UT WOS:000300277000004
PM 22764449
DA 2022-11-30
ER

PT J
AU Shah, AR
   Del Priore, LV
AF Shah, A. R.
   Del Priore, L. V.
TI Duration of action of intravitreal ranibizumab and bevacizumab in
   exudative AMD eyes based on macular volume measurements
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID CHOROIDAL NEOVASCULARIZATION; BEVACKUMAB AVASTIN; DEGENERATION;
   PHARMACOKINETICS; EDEMA; LUCENTIS; RETINA
AB Background/aims: Sequential macular volume and central foveal point thickness (CFPT) measurements on optical coherence tomography (OCT) were used to determine the efficacy and duration of action of ranibizumab versus bevacizumab in wet age-related macular degeneration (AMD).
   Methods: Retrospective chart review of patients who received their first treatment of intravitreal ranibizumab or bevacizumab for exudative AMD. 316 patients (202 ranibizumab; 114 bevacizumab) who received 823 injections (313 ranibizumab; 510 bevacizumab) were identified. 74 patients had pre- and post-treatment OCTs performed to determine CFPT and macular volume changes.
   Results: Ranibizumab caused a significant reduction in CFPT (278 (SD 84) before treatment vs 227 (80) mm after treatment; p = 0.001) and macular volume (7.22 (0.96) vs 6.69 (0.74) mm(3); p = 0.002). Intravitreal bevacizumab caused a similar reduction in CFPT (288 (94) vs 220 (55) mm; p = 0.008) and macular volume (7.36 (1.08) vs 6.50 (0.42) mm(3); p<0.001). The mean duration of action was 74.0 (19.1) days for ranibizumab compared with 101.8 (16.6) days for bevacizumab (p = 0.036; t test). The ratio of the relative duration of action of bevacizumab versus ranibizumab was 1.40 (0.19).
   Conclusions: Both drugs are equally effective at reducing CFPT or macular volume. Bevacizumab appears to take longer to achieve the minimum macular volume, and its effects take longer to wear off, suggesting it can be given less often.
C1 [Shah, A. R.; Del Priore, L. V.] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
C3 Columbia University
RP Del Priore, LV (通讯作者)，635 W 165th St, New York, NY 10032 USA.
EM ldelpriore@yahoo.com
FU Eye Surgery Fund; Robert L. Burch III Fund; Foundation Fighting
   Blindness; Doris Duke Foundation
FX Supported by the Eye Surgery Fund, the Robert L. Burch III Fund, the
   Foundation Fighting Blindness, the Doris Duke Foundation and
   unrestricted funds from Research to Prevent Blindness.
CR Adan A, 2007, GRAEF ARCH CLIN EXP, V245, P1873, DOI 10.1007/s00417-007-0637-y
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NR 24
TC 26
Z9 27
U1 0
U2 5
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 2009
VL 93
IS 8
BP 1027
EP 1032
DI 10.1136/bjo.2008.149674
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 474RP
UT WOS:000268302000009
PM 19429594
DA 2022-11-30
ER

PT J
AU Elliot, S
   Catanuto, P
   Fernandez, P
   Espinosa-Heidmann, D
   Karl, M
   Korach, K
   Cousins, SW
AF Elliot, Sharon
   Catanuto, Paola
   Fernandez, Pedro
   Espinosa-Heidmann, Diego
   Karl, Michael
   Korach, Kenneth
   Cousins, Scott W.
TI Subtype specific estrogen receptor action protects against changes in
   MMP-2 activation in mouse retinal pigmented epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE estrogen receptor; age related macular degeneration; extracellular
   matrix; estrogen; matrix metalloproteinases; tissue inhibitors of
   metalloproteinases
ID FINGER TRANSCRIPTION FACTORS; NONLETHAL OXIDANT INJURY; MATRIX
   METALLOPROTEINASE-2; ER-ALPHA; EXTRACELLULAR-MATRIX; EXPRESSION;
   MT1-MMP; BETA; SP1; GLOMERULOSCLEROSIS
AB Eyes with age-related macular degeneration (AMD) demonstrate accumulation of specific deposits and extracellular matrix (ECM) molecules under the retinal pigment epithelium (RPE). AMD is about two times more prevalent in aging postmenopausal women. Therefore we studied whether 17 beta-estradiol (E-2) modulates the expression and activity of the trimolecular complex (MMP-2, TIMP-2 and MMP-14), molecules which are of major importance for ECM turnover in RPE. We used cell lines isolated from estrogen receptor knockout mice (ERKO) to determine which ER (estrogen receptor) subtype was important for ECM regulation in RPE cells.
   We found that mouse RPE sheets had higher baseline MMP-2 activity in the presence of ER beta. This correlated with higher MMP-2 activity in RPE cell lines isolated from ERKO alpha. mice. Exposure to E-2 increased MMP-2 activity in mouse RPE cell lines, In addition E-2 increased transcriptional activation of the MMP-2 promoter through a functional Sp1 site which required the presence of ER beta, but not ER alpha. E-2 also maintained levels of pro MMP-2, and MMP-14 and TIMP-2 activity after oxidant injury. Since the direct effects of E-2 on MMP-2 transcriptional activation and the regulation of the trimolecular complex after oxidant-induced injury requires ER beta, this receptor subtype may have a role as a potential therapeutic target to prevent changes in activation of MMP-2. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Elliot, Sharon; Catanuto, Paola; Fernandez, Pedro; Espinosa-Heidmann, Diego; Karl, Michael] Univ Miami, Miller Sch Med, Lab Sex & Gender Differences Hlth & Dis, Miami, FL 33136 USA.
   [Korach, Kenneth] Natl Inst Environm Hlth Sci, Receptor Biol Lab, Res Triangle Pk, NC 27709 USA.
   [Cousins, Scott W.] Duke Univ, Ctr Eye, Duke Ctr Mascula Dis, Durham, NC USA.
C3 University of Miami; National Institutes of Health (NIH) - USA; NIH
   National Institute of Environmental Health Sciences (NIEHS); Duke
   University
RP Elliot, S (通讯作者)，Univ Miami, Miller Sch Med, Lab Sex & Gender Differences Hlth & Dis, Rosensteil Med Bldg Room 1043,R104, Miami, FL 33136 USA.
EM selliot@med.miami.edu
OI Korach, Kenneth/0000-0002-7765-418X
FU NEI NIH HHS [P30 EY005722, P30 EY005722-22, R01 EY014477-01A1, R01
   EY014477-02, R01 EY014477, R01 EY14477-04, R01 EY014477-04, R01
   EY014477-03] Funding Source: Medline; NATIONAL EYE INSTITUTE
   [R01EY014477, P30EY005722] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [ZIAES070065] Funding Source:
   NIH RePORTER
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NR 47
TC 19
Z9 20
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 APR
PY 2008
VL 86
IS 4
BP 653
EP 660
DI 10.1016/j.exer.2008.01.010
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 295DB
UT WOS:000255454100012
PM 18313050
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Kolko, M
   Prause, JU
   Bazan, NG
   Heegaard, S
AF Kolko, Miriam
   Prause, Jan U.
   Bazan, Nicolas G.
   Heegaard, Steffen
TI Human secretory phospholipase A(2), group IB in normal eyes and in eye
   diseases
SO ACTA OPHTHALMOLOGICA SCANDINAVICA
LA English
DT Article
DE hGIB; human eye; retinal pigment epithelium migration; endothelial
   dystrophy
ID ROD OUTER SEGMENTS; MEMBRANE-RECEPTOR; RAT RETINA; CELL-DEATH;
   EXPRESSION; CLONING; BRAIN; GLUTAMATE; CHANNELS; MOUSE
AB Secretory phospholipases A(2) (sPLA(2)) are enzymes involved in lipid turnover. We recently identified sPLA(2) group IB (GIB) in the rat retina as well as in cerebral neurons and found upregulation to occur in response to light damage and seizures, respectively. The purpose of the present study was to identify human GIB (hGIB) in the normal human eye and investigate the pattern of expression in patients with eye diseases involving hGIB-rich cells.
   Human GIB mRNA was identified in the human retina by means of in situ hybridization and polymerase chain reaction. Antibodies against hGIB were obtained and immunohistochemical staining was performed on paraffin-embedded sections of normal and pathological eyes. Donor eyes from patients with descemetization of the cornea, Fuchs' corneal endothelial dystrophy, age-related macular degeneration, malignant choroidal melanoma, retinitis pigmentosa and glaucoma were evaluated.
   Expression of hGIB was found in various cells of the eye. The most abundant expression was found in retinal pigment epithelium (RPE) cells, the inner photoreceptor segments, ganglion cells and the corneal endothelium. We explored diseases involving hGIB-rich cells and found downregulation of hGIB in proliferating RPE cells as well as in diseased corneal endothelial cells.
   Human GIB is highly expressed in cells with neurodermal origin. The pattern of expression of hGIB in diseases involving hGIB-rich cells demonstrated a downregulation of hGIB in migrating RPE cells and in diseased corneal endothelium.
C1 Univ Copenhagen, Eye Pathol Inst, DK-2100 Copenhagen, Denmark.
   Louisiana State Univ, Hlth Sci Ctr, Neurosci Ctr Excellence, Sch Med, New Orleans, LA USA.
   Louisiana State Univ, Hlth Sci Ctr, Dept Ophthalmol, Sch Med, New Orleans, LA USA.
C3 University of Copenhagen; Louisiana State University System; Louisiana
   State University Health Sciences Center New Orleans; Louisiana State
   University System; Louisiana State University Health Sciences Center New
   Orleans
RP Kolko, M (通讯作者)，Univ Copenhagen, Eye Pathol Inst, Frederik D V Vej 11,1st Floor, DK-2100 Copenhagen, Denmark.
EM mkolko@dadlnet.dk
RI Bazan, Nicolas/AAN-4121-2020
OI Bazan, Nicolas/0000-0002-9243-5444; Kolko, Miriam/0000-0001-8697-0734
FU NATIONAL EYE INSTITUTE [R01EY005121] Funding Source: NIH RePORTER; NEI
   NIH HHS [EY05121] Funding Source: Medline
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NR 28
TC 13
Z9 14
U1 0
U2 0
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 MAY
PY 2007
VL 85
IS 3
BP 317
EP 323
DI 10.1111/j.1600-0420.2006.00809.x
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 163HM
UT WOS:000246150700013
PM 17488462
OA Bronze
DA 2022-11-30
ER

PT J
AU Foy, RC
   Foot, B
   Francis, J
   Chakravarthy, U
   Wormald, RPL
AF Foy, RC
   Foot, B
   Francis, J
   Chakravarthy, U
   Wormald, RPL
TI Trends in provision of photodynamic therapy and clinician attitudes: a
   tracker survey of a new health technology
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION;
   VERTEPORFIN
AB Background: There has been debate about the cost-effectiveness of photodynamic therapy (PDT), a treatment for neovascular age-related macular degeneration. We have been monitoring trends for the provision of PDT in the UK National Health Service. The fourth annual 'tracker' survey took place as definitive National Institute for Clinical Excellence ( NICE) guidance was issued. We assessed trends in PDT provision up to the point of release of the NICE guidance and identified likely sources of pressure on ophthalmologists to provide PDT.
   Methods: National postal questionnaire survey of clinicians with potential responsibility for PDT provision. The survey explored reported local provision, beliefs about the effectiveness of PDT and what sources of opinion might influence attitudes towards providing PDT.
   Results: The response rate was 73% (111/150). Almost half of the surveyed ophthalmology units routinely provided PDT, as part of a trend of steady growth in provision. The proportion of respondents who believed that further proof of effectiveness was required has also declined despite the absence of any new substantial evidence. Attitudes towards providing PDT were positive, on average, and were more strongly associated with perceived social pressure from local colleagues than from other sources. Local colleagues were seen as being most approving of PDT.
   Conclusion: Those responsible for implementing the NICE guidance need to address ophthalmologists' beliefs about the evidence of effectiveness for PDT and draw upon supportive local individuals or networks to enhance the credibility of the guidance.
C1 Royal Coll Ophthalmologists, London, England.
   Univ Newcastle Upon Tyne, Ctr Hlth Serv Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   Univ Aberdeen, Hlth Serv Res Unit, Aberdeen AB9 1FX, Scotland.
   Queens Univ Belfast, Belfast, Antrim, North Ireland.
   Royal Victoria Hosp, Belfast BT12 6BA, Antrim, North Ireland.
   Moorfields Eye Hosp, London, England.
C3 Newcastle University - UK; University of Aberdeen; Queens University
   Belfast; University of London; University College London; Moorfields Eye
   Hospital NHS Foundation Trust
RP Foot, B (通讯作者)，Royal Coll Ophthalmologists, London, England.
EM R.C.Foy@newcastle.ac.uk; bosu@msn.com; j.francis@abdn.ac.uk;
   U.Chakravarthy@queens-belfast.ac.uk; r.wormald@ucl.ac.uk
RI Francis, Jill/AHE-6998-2022
OI Foy, Robbie/0000-0003-0605-7713; Francis, Jill/0000-0001-5784-8895;
   Chakravarthy, Usha/0000-0002-2606-3734
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NR 18
TC 0
Z9 0
U1 0
U2 2
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD MAY 10
PY 2005
VL 5
AR 34
DI 10.1186/1472-6963-5-34
PG 5
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA 932HL
UT WOS:000229544700001
PM 15885142
OA Green Published, gold, Green Accepted
DA 2022-11-30
ER

PT J
AU Mueller-Buehl, AM
   Buehner, T
   Pfarrer, C
   Deppe, L
   Peters, L
   Dick, BH
   Joachim, SC
AF Mueller-Buehl, Ana M.
   Buehner, Torsten
   Pfarrer, Christiane
   Deppe, Leonie
   Peters, Laura
   Dick, Burkhard H.
   Joachim, Stephanie C.
TI Hypoxic Processes Induce Complement Activation via Classical Pathway in
   Porcine Neuroretinas
SO CELLS
LA English
DT Article
DE hypoxia; oxidative stress; complement system; microglia; inflammation
ID OXIDATIVE STRESS; OPTIC-NERVE; GLAUCOMA; RETINA; MODEL; DAMAGE;
   MECHANISMS; APOPTOSIS; NEURONS; MURINE
AB Considering the fact that many retinal diseases are yet to be cured, the pathomechanisms of these multifactorial diseases need to be investigated in more detail. Among others, oxidative stress and hypoxia are pathomechanisms that take place in retinal diseases, such as glaucoma, age-related macular degeneration, or diabetic retinopathy. In consideration of these diseases, it is also evidenced that the immune system, including the complement system and its activation, plays an important role. Suitable models to investigate neuroretinal diseases are organ cultures of porcine retina. Based on an established model, the role of the complement system was studied after the induction of oxidative stress or hypoxia. Both stressors led to a loss of retinal ganglion cells (RGCs) accompanied by apoptosis. Hypoxia activated the complement system as noted by higher C3(+) and MAC(+) cell numbers. In this model, activation of the complement cascade occurred via the classical pathway and the number of C1q(+) microglia was increased. In oxidative stressed retinas, the complement system had no consideration, but strong inflammation took place, with elevated TNF, IL6, and IL8 mRNA expression levels. Together, this study shows that hypoxia and oxidative stress induce different mechanisms in the porcine retina inducing either the immune response or an inflammation. Our findings support the thesis that the immune system is involved in the development of retinal diseases. Furthermore, this study is evidence that both approaches seem suitable models to investigate undergoing pathomechanisms of several neuroretinal diseases.
C1 [Mueller-Buehl, Ana M.; Buehner, Torsten; Deppe, Leonie; Peters, Laura; Dick, Burkhard H.; Joachim, Stephanie C.] Ruhr Univ Bochum, Univ Eye Hosp, Expt Eye Res Inst, D-44892 Bochum, Germany.
   [Buehner, Torsten; Pfarrer, Christiane] Univ Vet Med Hannover, Inst Anat, D-30559 Hannover, Germany.
C3 Ruhr University Bochum; University of Veterinary Medicine Hannover,
   Foundation
RP Joachim, SC (通讯作者)，Ruhr Univ Bochum, Univ Eye Hosp, Expt Eye Res Inst, D-44892 Bochum, Germany.
EM Ana.Mueller-Buehl@rub.de; tb@tierarzt-buehner.de;
   Christiane.Pfarrer@tiho-hannover.de; Leonie.Deppe@rub.de;
   Laura.Peters@rub.de; Burkhard.Dick@kk-bochum.de;
   stephanie.joachim@rub.de
OI Joachim, Stephanie/0000-0001-7056-0829; Dick,
   Burkhard/0000-0001-7551-7395
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NR 66
TC 1
Z9 1
U1 5
U2 9
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD DEC
PY 2021
VL 10
IS 12
AR 3575
DI 10.3390/cells10123575
PG 24
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA XX3WI
UT WOS:000736229900001
PM 34944083
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Cano, M
   Datta, S
   Wang, L
   Liu, TY
   Flores-Bellver, M
   Sachdeva, M
   Sinha, D
   Handa, JT
AF Cano, Marisol
   Datta, Sayantan
   Wang, Lei
   Liu, Tongyun
   Flores-Bellver, Miguel
   Sachdeva, Mira
   Sinha, Debasish
   Handa, James T.
TI Nrf2 deficiency decreases NADPH from impaired IDH shuttle and pentose
   phosphate pathway in retinal pigmented epithelial cells to magnify
   oxidative stress-induced mitochondrial dysfunction
SO AGING CELL
LA English
DT Article
DE aging; mitochondria; oxidative stress; reactive oxygen species
ID NICOTINAMIDE NUCLEOTIDE TRANSHYDROGENASE; HYDROGEN-PEROXIDE PRODUCTION;
   MACULAR DEGENERATION; PROGRESSIVE STAGES; POOLED FINDINGS; RISK-FACTORS;
   GLUTATHIONE; ACTIVATION; APOPTOSIS; SMOKING
AB The nuclear factor-erythroid 2-related factor-2 (Nrf2), a major antioxidant transcription factor, is decreased in several age-related diseases including age-related macular degeneration (AMD), the most common cause of blindness among the elderly in western society. Since Nrf2's mito-protective response is understudied, we investigated its antioxidant response on mitochondria. Control and Nrf2-deficient retinal pigmented epithelial (RPE) cells were compared after treating with cigarette smoke extract (CSE). Mitochondrial antioxidant abundance and reactive oxygen species (ROS) were quantified. Mitochondrial function was assessed by TMRM assay, NADPH, electron transport chain activity, and Seahorse. Results were corroborated in Nrf2(-/-) mice and relevance to AMD was provided by immunohistochemistry of human globes. CSE induced mitochondrial ROS to impair mitochondrial function. H2O2 increase in particular, was magnified by Nrf2 deficiency, and corresponded with exaggerated mitochondrial dysfunction. While Nrf2 did not affect mitochondrial antioxidant abundance, oxidized PRX3 was magnified by Nrf2 deficiency due to decreased NADPH from decreased expression of IDH2 and pentose phosphate pathway (PPP) genes. With severe CSE stress, intrinsic apoptosis was activated to increase cell death. PPP component TALDO1 immunolabeling was decreased in dysmorphic RPE of human AMD globes. Despite limited regulation of mitochondrial antioxidant expression, Nrf2 influences PPP and IDH shuttle activity that indirectly supplies NADPH for the TRX2 system. These results provide insight into how Nrf2 deficiency impacts the mitochondrial antioxidant response, and its role in AMD pathobiology.
C1 [Cano, Marisol; Datta, Sayantan; Wang, Lei; Liu, Tongyun; Flores-Bellver, Miguel; Sachdeva, Mira; Handa, James T.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD 21210 USA.
   [Sinha, Debasish] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Baltimore, MD 21210 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); University of
   Pittsburgh
RP Handa, JT (通讯作者)，400 N Broadway,Smith Bldg 3015, Baltimore, MD 21287 USA.
EM jthanda@jhmi.edu
OI Flores-Bellver, Miguel/0000-0003-3421-3699
FU NEI [EY R01EY027691, EY001765, K99 EY029010]; Macular Degeneration
   Foundation; Research to Prevent Blindness; Merlau family and Aleda
   Wright
FX NEI EY R01EY027691 (JTH), EY001765 (Core Grant, Wilmer Eye Institute),
   K99 EY029010 (SD), Macular Degeneration Foundation (JTH), Research to
   Prevent Blindness (Wilmer Eye Institute), and by the Merlau family and
   Aleda Wright. JTH is the Robert Bond Welch Professor
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NR 65
TC 12
Z9 12
U1 4
U2 10
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD AUG
PY 2021
VL 20
IS 8
AR e13444
DI 10.1111/acel.13444
EA JUL 2021
PG 15
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA UB5AD
UT WOS:000678548600001
PM 34313391
OA Green Published
DA 2022-11-30
ER

PT J
AU Arens-Arad, T
   Farah, N
   Lender, R
   Moshkovitz, A
   Flores, T
   Palanker, D
   Mandel, Y
AF Arens-Arad, Tamar
   Farah, Nairouz
   Lender, Rivkah
   Moshkovitz, Avital
   Flores, Thomas
   Palanker, Daniel
   Mandel, Yossi
TI Cortical Interactions between Prosthetic and Natural Vision
SO CURRENT BIOLOGY
LA English
DT Article
ID RECEPTIVE-FIELD PROPERTIES; VISUAL-CORTEX; FACILITATION; SUPPRESSION;
   ORGANIZATION; SENSITIVITY; ADAPTATION; PHYSIOLOGY; PARALLEL; ANIMALS
AB Outer retinal degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), are among the leading causes of incurable blindness in the Western world [1]. Retinal prostheses have been shown to restore some useful vision by electrically stimulating the remaining retinal neurons [2]. In contrast to inherited retinal degenerative diseases (e.g., RP), typically leading to a complete loss of the visual field, in AMD patients the disease is localized to the macula, leaving the peripheral vision intact. Implanting a retinal prosthesis in the central macula in AMD patients [3, 4] leads to an intriguing situation where the patient's central retina is stimulated electrically, whereas the peripheral healthy retina responds to natural light stimulation. An important question is whether the visual cortex responds to these two concurrent stimuli similarly to the interaction between two adjacent natural light stimuli projected onto healthy retina. Here, we investigated the cortical interactions between prosthetic and natural vision based on visually evoked potentials (VEPs) recorded in rats implanted with photovoltaic subretinal implants. Using this model, where prosthetic and natural vision information are combined in the visual cortex, we observed striking similarities in the interactions of natural and prosthetic vision, including similar effect of background illumination, linear summation of non patterned stimuli, and lateral inhibition with spatial patterns [5], which increased with target contrast. These results support the idea of combined prosthetic and natural vision in restoration of sight for AMD patients.
C1 [Arens-Arad, Tamar; Farah, Nairouz; Lender, Rivkah; Moshkovitz, Avital; Mandel, Yossi] Bar Ilan Univ, Sch Optometry & Vis Sci, Fac Life Sci, Max Ve Anna Webb St, IL-5290002 Ramat Gan, Israel.
   [Arens-Arad, Tamar; Farah, Nairouz; Lender, Rivkah; Moshkovitz, Avital; Mandel, Yossi] Bar Ilan Univ, Bar Ilan Inst Nanotechnol & Adv Mat BINA, Max Ve Anna Webb St, IL-5290002 Ramat Gan, Israel.
   [Flores, Thomas; Palanker, Daniel] Stanford Univ, Hansen Expt Phys Lab, 452 Lomita Mall, Stanford, CA 94305 USA.
   [Palanker, Daniel] Stanford Univ, Ophthalmol, 452 Lomita Mall, Stanford, CA 94305 USA.
C3 Bar Ilan University; Bar Ilan University; Stanford University; Stanford
   University
RP Mandel, Y (通讯作者)，Bar Ilan Univ, Sch Optometry & Vis Sci, Fac Life Sci, Max Ve Anna Webb St, IL-5290002 Ramat Gan, Israel.; Mandel, Y (通讯作者)，Bar Ilan Univ, Bar Ilan Inst Nanotechnol & Adv Mat BINA, Max Ve Anna Webb St, IL-5290002 Ramat Gan, Israel.
EM yossi.mandel@biu.ac.il
OI Palanker, Daniel/0000-0002-0480-3025
FU Israeli Science Foundation (ISF) [157/16]; ERC [755748]; Israeli
   Ministry of Defense; Israeli Ministry of Science and Technology
FX The project was supported by Israeli Science Foundation (ISF no.
   157/16), ERC starter grant 755748, Israeli Ministry of Defense, and
   Israeli Ministry of Science and Technology.
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NR 44
TC 6
Z9 7
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD JAN 6
PY 2020
VL 30
IS 1
BP 176
EP +
DI 10.1016/j.cub.2019.11.028
PG 9
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 KA3IK
UT WOS:000505692200034
PM 31883811
OA Bronze, Green Accepted
DA 2022-11-30
ER

PT J
AU Zhou, XZ
   Wei, YT
   Qiu, S
   Xu, Y
   Zhang, T
   Zhang, SC
AF Zhou, Xuezhi
   Wei, Yantao
   Qiu, Suo
   Xu, Yue
   Zhang, Ting
   Zhang, Shaochong
TI Propofol Decreases Endoplasmic Reticulum Stress-Mediated Apoptosis in
   Retinal Pigment Epithelial Cells
SO PLOS ONE
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; CEREBRAL-ISCHEMIA; ER STRESS; MITOCHONDRIAL
   DYSFUNCTION; MACULAR DEGENERATION; PROAPOPTOTIC BAX; UP-REGULATION;
   IN-VITRO; KAPPA-B; BCL-2
AB Age-related macular degeneration (AMD) is the major cause of loss of sight globally. There is currently no effective treatment available. Retinal pigment epithelial (RPE) cells are an important part of the outer blood-retina barrier and their death is a determinant of AMD. Propofol, a common clinically used intravenous anesthetic agent, has been shown to act as an efficacious neuroprotective agent with antioxidative and anti-inflammatory properties in vivo and in vitro. However, little is known about its effects on RPE cells. The purpose of our research was to investigate whether propofol could protect RPE cells from apoptosis through endoplasmic reticulum (ER) stress-dependent pathways. To this end, prior to stimulation with thapsigargin (TG), ARPE-19 cells were pretreated with varying concentrations of propofol. A protective effect of propofol in TG-treated ARPE-9 was apparent, TUNEL and flow cytometric assays showed decreased apoptosis. We further demonstrated that propofol pretreatment attenuated or inhibited the effects caused by TG, such as upregulation of Bax, BiP, C/EBP homologous protein (CHOP), active caspase 12, and cleaved caspase 3, and downregulation of Bcl2. It also decreased the TG-induced levels of ER stress-related molecules such as p-PERK, p-eIF2 alpha, and ATF4. Furthermore, it downregulated the expression of nuclear factor kappa B (NF-kappa B). This study elucidated novel propofol-induced cellular mechanisms for antiapoptotic activities in RPE cells undergoing ER stress and demonstrated the potential value of using propofol in the treatment of AMD.
C1 [Zhou, Xuezhi; Wei, Yantao; Qiu, Suo; Xu, Yue; Zhang, Ting; Zhang, Shaochong] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
C3 Sun Yat Sen University
RP Zhang, SC (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
EM zhshaochong@sohu.com
OI Zhou, Xuezhi/0000-0002-4501-1817
FU Fund for National Natural Science Foundation [81441025, 81170866]
FX This study was supported by the Fund for National Natural Science
   Foundation (81441025) and the Fund for National Natural Science
   Foundation (81170866).
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NR 54
TC 12
Z9 13
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 JUN 16
PY 2016
VL 11
IS 6
AR e0157590
DI 10.1371/journal.pone.0157590
PG 17
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DO8JO
UT WOS:000378029800103
PM 27311010
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Fan, RZ
   Wang, YF
   Yan, Q
   Ding, Y
   Weeks, DE
   Lu, ZH
   Ren, HB
   Cook, RJ
   Xiong, MM
   Swaroop, A
   Chew, EY
   Chen, W
AF Fan, Ruzong
   Wang, Yifan
   Yan, Qi
   Ding, Ying
   Weeks, Daniel E.
   Lu, Zhaohui
   Ren, Haobo
   Cook, Richard J.
   Xiong, Momiao
   Swaroop, Anand
   Chew, Emily Y.
   Chen, Wei
TI Gene-Based Association Analysis for Censored Traits Via Fixed Effect
   Functional Regressions
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE rare variants; common variants; association study; complex diseases;
   functional data analysis; Cox models
ID LINEAR-MODELS; QUANTITATIVE TRAITS; MACULAR DEGENERATION; VARIANTS;
   LEVEL
AB Genetic studies of survival outcomes have been proposed and conducted recently, but statistical methods for identifying genetic variants that affect disease progression are rarely developed. Motivated by our ongoing real studies, here we develop Cox proportional hazard models using functional regression (FR) to perform gene-based association analysis of survival traits while adjusting for covariates. The proposed Cox models are fixed effect models where the genetic effects of multiple genetic variants are assumed to be fixed. We introduce likelihood ratio test (LRT) statistics to test for associations between the survival traits and multiple genetic variants in a genetic region. Extensive simulation studies demonstrate that the proposed Cox RF LRT statistics have well-controlled type I error rates. To evaluate power, we compare the Cox FR LRT with the previously developed burden test (BT) in a Cox model and sequence kernel association test (SKAT), which is based on mixed effect Cox models. The Cox FR LRT statistics have higher power than or similar power as Cox SKAT LRT except when 50%/50% causal variants had negative/positive effects and all causal variants are rare. In addition, the Cox FR LRT statistics have higher power than Cox BT LRT. The models and related test statistics can be useful in the whole genome and whole exome association studies. An age-related macular degeneration dataset was analyzed as an example. Genet Epidemiol 40: 133-143, 2016. (C) 2016 Wiley Periodicals, Inc.
C1 [Fan, Ruzong; Wang, Yifan; Lu, Zhaohui] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Biostat & Bioinformat Branch, NIH, Bethesda, MD 20892 USA.
   [Yan, Qi; Chen, Wei] Univ Pittsburgh, Childrens Hosp Pittsburgh, Div Pulm Med Allergy & Immunol, Pittsburgh, PA 15224 USA.
   [Ding, Ying; Weeks, Daniel E.; Chen, Wei] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15224 USA.
   [Weeks, Daniel E.; Chen, Wei] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15224 USA.
   [Ren, Haobo] Regeneron Pharmaceut Inc, Basking Ridge, NJ USA.
   [Cook, Richard J.] Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada.
   [Xiong, Momiao] Univ Texas Houston, Human Genet Ctr, Houston, TX USA.
   [Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
   [Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver
   National Institute of Child Health & Human Development (NICHD);
   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; University of
   Waterloo; University of Texas System; University of Texas Health Science
   Center Houston; National Institutes of Health (NIH) - USA; NIH National
   Eye Institute (NEI); National Institutes of Health (NIH) - USA; NIH
   National Eye Institute (NEI)
RP Fan, RZ (通讯作者)，Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Biostat & Bioinformat Branch, NIH, Bethesda, MD 20892 USA.; Chen, W (通讯作者)，Univ Pittsburgh, Childrens Hosp Pittsburgh, Div Pulm Med Allergy & Immunol, Pittsburgh, PA 15224 USA.
EM fanr@mail.nih.gov; wei.chen@chp.edu
RI Chen, Wei/AAX-5994-2020; Weeks, Daniel E/B-2995-2012
OI Chen, Wei/0000-0001-7196-8703; Weeks, Daniel E/0000-0001-9410-7228;
   Swaroop, Anand/0000-0002-1975-1141; Ding, Ying/0000-0003-1352-1000;
   Cook, Richard/0000-0002-1414-4908
FU Intramural NIH HHS [Z99 HD999999, ZIA HD008918-02, ZIA HD008918-03]
   Funding Source: Medline; NEI NIH HHS [R01 EY024226, R01EY024226] Funding
   Source: Medline; NHGRI NIH HHS [R01HG007358, R01 HG007358] Funding
   Source: Medline; EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD
   HEALTH & HUMAN DEVELOPMENT [ZIAHD008918] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R01EY024226, ZIAEY000546] Funding Source: NIH
   RePORTER; NATIONAL HUMAN GENOME RESEARCH INSTITUTE [R01HG007358] Funding
   Source: NIH RePORTER
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NR 35
TC 11
Z9 11
U1 0
U2 7
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD FEB
PY 2016
VL 40
IS 2
BP 133
EP 143
DI 10.1002/gepi.21947
PG 11
WC Genetics & Heredity; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Mathematical & Computational Biology
GA DB7VS
UT WOS:000368725400005
PM 26782979
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Sun, JN
   Mandai, M
   Kamao, H
   Hashiguchi, T
   Shikamura, M
   Kawamata, S
   Sugita, S
   Takahashi, M
AF Sun, Jianan
   Mandai, Michiko
   Kamao, Hiroyuki
   Hashiguchi, Tomoyo
   Shikamura, Masayuki
   Kawamata, Shin
   Sugita, Sunao
   Takahashi, Masayo
TI Protective Effects of Human iPS-Derived Retinal Pigmented Epithelial
   Cells in Comparison with Human Mesenchymal Stromal Cells and Human
   Neural Stem Cells on the Degenerating Retina in rd1 Mice
SO STEM CELLS
LA English
DT Article
DE Transplantation; Cell-based therapy; Induced pluripotent stem cells;
   Retinal pigment epithelium cells; Retinal degeneration; Pigment
   epithelium-derived factor
ID NERVE GROWTH-FACTOR; PHOTORECEPTOR DEGENERATION; INTRAVITREAL
   BEVACIZUMAB; NEUROTROPHIC FACTOR; PROGENITOR CELLS; VISUAL FUNCTIONS;
   GENE-EXPRESSION; FACTOR DELAYS; FACTOR PEDF; RAT MODEL
AB Retinitis pigmentosa (RP) is a group of visual impairments characterized by progressive rod photoreceptor cell loss due to a genetic background. Pigment epithelium-derived factor (PEDF) predominantly secreted by the retinal pigmented epithelium (RPE) has been reported to protect photoreceptors in retinal degeneration models, including rd1. In addition, clinical trials are currently underway outside Japan using human mesenchymal stromal cells and human neural stem cells to protect photoreceptors in RP and dry age-related macular degeneration, respectively. Thus, this study aimed to investigate the rescue effects of induced pluripotent stem (iPS)-RPE cells in comparison with those types of cells used in clinical trials on photoreceptor degeneration in rd1 mice. Cells were injected into the subretinal space of immune-suppressed 2-week-old rd1 mice. The results demonstrated that human iPS-RPE cells significantly attenuated photoreceptor degeneration on postoperative days (PODs) 14 and 21 and survived longer up to at least 12 weeks after operation than the other two types of graft cells with less immune responses and apoptosis. The mean PEDF concentration in the intraocular fluid in RPE-transplanted eyes was more than 1 mu g/ml at PODs 14 and 21, and this may have contributed to the protective effect of RPE transplantation. Our findings suggest that iPS-RPE cells serve as a competent source to delay photoreceptor degeneration through stable survival in degenerating ocular environment and by releasing neuroprotective factors such as PEDF.
C1 [Sun, Jianan; Mandai, Michiko; Kamao, Hiroyuki; Hashiguchi, Tomoyo; Sugita, Sunao; Takahashi, Masayo] RIKEN Ctr Dev Biol CDB, Lab Retinal Regenerat, Kobe, Hyogo, Japan.
   [Sun, Jianan] Kyoto Univ, Grad Sch Med, Applicat Biol & Regenerat Med, Kyoto, Japan.
   [Kamao, Hiroyuki] Kawasaki Med Sch, Dept Ophthalmol, Kurashiki, Okayama, Japan.
   [Shikamura, Masayuki; Kawamata, Shin] Fdn Biomed Res & Innovat, Res & Dev Ctr Cell Therapy, Kobe, Hyogo, Japan.
C3 RIKEN; Kyoto University; Kawasaki Medical School; Institute for
   Biomedical Research & Innovation (IBRI)
RP Mandai, M (通讯作者)，RIKEN Ctr Dev Biol, Lab Retinal Regenerat, Chuo Ku, 2-2-3 Minatojima Minamimachi, Kobe, Hyogo 6500047, Japan.
EM mmandai@cdb.riken.jp
OI Kamao, Hiroyuki/0000-0002-2194-7063; kawamata, shin/0000-0001-5148-1949
FU Japanese Government (Monbukagakusho: MEXT) Scholarship Program; MEXT
FX We thank Tadao Maeda, Kyoko Iseki, Noriko Sakai, and Satoshi Okamoto for
   technical assistance and advice and all members of the Takahashi
   Laboratory for valuable discussion and comments. J.S. also thanks the
   Japanese Government (Monbukagakusho: MEXT) Scholarship Program. This
   study was supported by a grant from the Project for Realization of
   Regenerative Medicine, MEXT.
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NR 83
TC 45
Z9 48
U1 1
U2 33
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD MAY
PY 2015
VL 33
IS 5
BP 1543
EP 1553
DI 10.1002/stem.1960
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA CG4XM
UT WOS:000353292600016
PM 25728228
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Chan, CM
   Huang, CH
   Li, HJ
   Hsiao, CY
   Su, CC
   Lee, PL
   Hung, CF
AF Chan, Chi-Ming
   Huang, Cheng-Hua
   Li, Hsin-Ju
   Hsiao, Chien-Yu
   Su, Ching-Chieh
   Lee, Pei-Lan
   Hung, Chi-Feng
TI Protective Effects of Resveratrol against UVA-Induced Damage in ARPE19
   Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; ACTIVATED POTASSIUM CHANNELS; MACULAR
   DEGENERATION; TRANS-RESVERATROL; INDUCED APOPTOSIS; ULTRAVIOLET;
   CYCLOOXYGENASE-2; INHIBITION; KERATINOCYTES; EXPRESSION
AB Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE) cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS) and generate oxidative injury; oxidative injury to the retinal pigment epithelium has been implicated to play a contributory role in age-related macular degeneration (AMD). Studies showed that resveratrol, an abundant and active component of red grapes, can protect several cell types from oxidative stress. In this study, adult RPE cells being treated with different concentrations of resveratrol were used to evaluate the protective effect of resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through flow cytometry analysis, we found that the generation of intracellular H2O2 induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a concentration-dependent manner. Results of Western blot analysis demonstrated that resveratrol lowered the activation of UVA-induced extracellular signal-regulated kinase, c-jun-NH2 terminal kinase and p38 kinase in RPE cells. In addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2) expression in RPE cells pretreated with resveratrol. Our observations suggest that resveratrol is effective in preventing RPE cells from being damaged by UVA radiation, and is worth considering for further development as a chemoprotective agent for the prevention of early AMD.
C1 [Chan, Chi-Ming; Huang, Cheng-Hua; Su, Ching-Chieh; Hung, Chi-Feng] Fu Jen Catholic Univ, Sch Med, New Taipei City 24205, Taiwan.
   [Chan, Chi-Ming] Cardinal Tien Hosp, Dept Ophthalmol, New Taipei City 23148, Taiwan.
   [Huang, Cheng-Hua] Cathay Gen Hosp, Dept Internal Med, Taipei 10630, Taiwan.
   [Li, Hsin-Ju] Fu Jen Catholic Univ, Dept Chemstry, New Taipei City 24205, Taiwan.
   [Hsiao, Chien-Yu] Chang Gung Univ Sci & Technol, Dept Nutr & Hlth Sci, Taoyuan 33303, Taiwan.
   [Hsiao, Chien-Yu] Chang Gung Univ Sci & Technol, Res Ctr Ind Human Ecol, Taoyuan 33303, Taiwan.
   [Su, Ching-Chieh] Fu Jen Catholic Univ, Grad Inst Appl Sci & Engn, New Taipei City 24205, Taiwan.
   [Su, Ching-Chieh] Cardinal Tien Hosp, Dept Internal Med, New Taipei City 23148, Taiwan.
   [Lee, Pei-Lan] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
C3 Fu Jen Catholic University; Cardinal Tien Hospital; Cathay General
   Hospital; Fu Jen Catholic University; Chang Gung University of Science &
   Technology; Chang Gung University of Science & Technology; Fu Jen
   Catholic University; Cardinal Tien Hospital; Boston University
RP Hung, CF (通讯作者)，Fu Jen Catholic Univ, Sch Med, New Taipei City 24205, Taiwan.
EM m212092001@tmu.edu.tw; infection@cgh.org.tw; sakumanatsumi@gmail.com;
   mozart@gw.cgust.edu.tw; suk.ccsu@gmail.com; hlittlem@gmail.com;
   skin@mail.fju.edu.tw
RI Chan, Chi-Ming/GWZ-3612-2022; Hung, Chi-Feng/AAL-4977-2021
OI Hung, Chi-Feng/0000-0003-3478-5451
FU Cardinal Tien Hospital [FU 10008]; Cathay General Hospital
FX This work was supported by the grant from Cardinal Tien Hospital (FU
   10008) and Cathay General Hospital.
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NR 42
TC 45
Z9 47
U1 1
U2 21
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 MAR
PY 2015
VL 16
IS 3
BP 5789
EP 5802
DI 10.3390/ijms16035789
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA CG0KQ
UT WOS:000352955900005
PM 25775159
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Xu, XD
   Li, KR
   Li, XM
   Yao, J
   Qin, J
   Yan, B
AF Xu, Xue-Dong
   Li, Ke-Ran
   Li, Xiu-Miao
   Yao, Jin
   Qin, Jiang
   Yan, Biao
TI Long non-coding RNAs: new players in ocular neovascularization
SO MOLECULAR BIOLOGY REPORTS
LA English
DT Article
DE Long non-coding RNA; Ocular neovascularization; Microarray analysis;
   Age-related macular degeneration
ID LARGE-SCALE PREDICTION; TRANSCRIPTION FACTORS; MOLECULAR-MECHANISMS;
   ANGIOGENESIS; EXPRESSION
AB Pathological neovascularization are the most prevalent causes of moderate or severe vision loss. Long non-coding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules involved in numerous biological processes and complicated diseases. However, the role of lncRNAs in ocular neovascularization is still unclear. Here, we constructed a murine model of ocular neovascularization, and determined lncRNA expression profiles using microarray analysis. We identified 326 or 51 lncRNAs that were significantly either up-regulated or down-regulated in the vaso-obliteration or neovascularization phase, respectively. Based on Pearson correlation analysis, lncRNAs/mRNAs co-expression networks were constructed. GO enrichment analysis of lncRNAs-co-expressed mRNAs indicated that the biological modules were correlated with chromosome organization, extracellular region and guanylate cyclase activator activity in the vaso-obliteration phase, and correlated with cell proliferation, extracellular region and guanylate cyclase regulator activity in the neovascularization phase. KEGG pathway analysis indicated that MAPK signaling was the most significantly enriched pathway in both phases. Importantly, Vax2os1 and Vax2os2 were not only dynamically expressed in the vaso-obliteration and neovascularization phases, but also significantly altered in the aqueous humor of patients with neovascular age-related macular degeneration (AMD), suggesting a potential role of lncRNAs in the regulation of ocular neovascularization. Taken together, this study provided novel insights into the molecular pathogenesis of ocular neovascularization. The intervention of dysregulated lncRNA could become a potential target for the prevention and treatment of ocular vascular diseases.
C1 [Xu, Xue-Dong; Li, Ke-Ran; Li, Xiu-Miao; Yao, Jin; Qin, Jiang; Yan, Biao] Nanjing Med Univ, Hosp Eye, Nanjing 210029, Jiangsu, Peoples R China.
C3 Nanjing Medical University
RP Qin, J (通讯作者)，Nanjing Med Univ, Hosp Eye, 138 Han Zhong Rd, Nanjing 210029, Jiangsu, Peoples R China.
EM jqin710@vip.sina.com; yanbiao1982@hotmail.com
FU National Natural Science Foundation of China [81300241, 81371055];
   National clinical key construction project [(2012) 649]; Medical Science
   and Technology Development Project Fund of Nanjing [ZKX 12047, YKK12207,
   YKK12208]
FX This work was generously supported by grants from the National Natural
   Science Foundation of China (Grant No. 81300241 to B.Y. and Grant No.
   81371055 to Q.J.), grants from the National clinical key construction
   project [Grant No. (2012) 649 to Q.J.], and grants from the Medical
   Science and Technology Development Project Fund of Nanjing (Grant No.
   ZKX 12047 to Q.J., Grant No. YKK12207 to G.F.-C., and Grant No. YKK12208
   to J.Y.).
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NR 38
TC 47
Z9 48
U1 0
U2 13
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0301-4851
EI 1573-4978
J9 MOL BIOL REP
JI Mol. Biol. Rep.
PD JUL
PY 2014
VL 41
IS 7
BP 4493
EP 4505
DI 10.1007/s11033-014-3320-5
PG 13
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA AK2XH
UT WOS:000338283000034
PM 24623407
DA 2022-11-30
ER

PT J
AU Ablonczy, Z
   Dahrouj, M
   Marneros, AG
AF Ablonczy, Zsolt
   Dahrouj, Mohammad
   Marneros, Alexander G.
TI Progressive dysfunction of the retinal pigment epithelium and retina due
   to increased VEGF-A levels
SO FASEB JOURNAL
LA English
DT Article
DE age-related macular degeneration; visual cycle; retinoids; choroidal
   neovascularization
ID AGE-RELATED MACULOPATHY; SUBRETINAL DRUSENOID DEPOSITS; MACULAR
   DEGENERATION; RANIBIZUMAB; PREVALENCE; EXPRESSION; EYES; RPE
AB Patients with nonexudative (dry) age-related macular degeneration (AMD) frequently also develop neovascular (wet) AMD, suggesting a common pathomechanism. Increased vascular endothelial growth factor A (VEGF-A) has been implicated in the pathogenesis of choroidal neovascularization (CNV) in neovascular AMD, while its role in nonexudative AMD that manifests with progressive retinal pigment epithelium (RPE) and photoreceptor degeneration is not well defined. Mice with overall increased VEGF-A levels develop progressive morphological features of both forms of AMD, suggesting that an increase in VEGF-A has a direct age-dependent adverse effect on RPE and photoreceptor function independently of its CNV-promoting proangiogenic effect. Here we provide evidence for this hypothesis and show that morphological RPE abnormalities and retinal thinning in mice with increased VEGF-A levels correlate with progressive age-dependent attenuation of visual function with abnormal electroretinograms and reduced retinal rhodopsin levels. Retinoid profiling revealed a progressive reduction of 11-cis and all-trans retinal in the retinas of these mice, consistent with an impaired retinoid transport between the RPE and photoreceptors. These findings suggest that increased VEGF-A leads to an age-dependent RPE and retinal dysfunction that occurs also at sites where no CNV lesions form. The data support a central role of increased VEGF-A not only in the pathogenesis of neovascular but also of nonexudative AMD.Ablonczy, Z., Dahrouj, M., Marneros, A. G. Progressive dysfunction of the retinal pigment epithelium and retina due to increased VEGF-A levels.
C1 [Ablonczy, Zsolt; Dahrouj, Mohammad] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Marneros, Alexander G.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.
   [Marneros, Alexander G.] Harvard Univ, Sch Med, Dept Dermatol, Charlestown, MA USA.
C3 Medical University of South Carolina; Harvard University; Massachusetts
   General Hospital; Harvard University
RP Marneros, AG (通讯作者)，CNY 149,Room 3-216,CBRC,MGH East,13thSt, Charlestown, MA 02129 USA.
EM amarneros@mgh.harvard.edu
OI Marneros, Alexander/0000-0003-3866-020X
FU U.S. National Institutes of Health (NIH)/National Eye Institute (NEI)
   [NEI R01-EY019297]; NIH/NEI [NEI R01-EY019065]; Medical Scientist
   Training Program at the Medical University of South Carolina (MUSC);
   NIH/National Institute of General Medical Sciences [T32 GM008716];
   Research to Prevent Blindness; South Carolina Lions Association;
   NATIONAL EYE INSTITUTE [R01EY019065, R01EY019297] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008716]
   Funding Source: NIH RePORTER
FX The authors thank Drs. Andras Nagy, Lucile Miquerol, and Annette Damert
   (University of Toronto, Toronto, ON, Canada) for providing
   VEGF-A<SUP>hyper</SUP> mice and VEGF-A<SUP>hypo</SUP> mice, Patrice
   Goletz for technical help, and Drs. Rosalie Crouch and Jie Fan for
   helpful discussions. This work was supported by a U.S. National
   Institutes of Health (NIH)/National Eye Institute (NEI) grant to A.G.M.
   (NEI R01-EY019297), an NIH/NEI grant to Z.A. (NEI R01-EY019065), funding
   from the Medical Scientist Training Program at the Medical University of
   South Carolina (MUSC; NIH/National Institute of General Medical Sciences
   grant T32 GM008716) to M. D., an unrestricted grant of Research to
   Prevent Blindness to the Department of Ophthalmology at MUSC, and the
   South Carolina Lions Association.
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NR 27
TC 42
Z9 43
U1 1
U2 7
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 MAY
PY 2014
VL 28
IS 5
BP 2369
EP 2379
DI 10.1096/fj.13-248021
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 AG3RA
UT WOS:000335336000037
PM 24558195
OA Green Published
DA 2022-11-30
ER

PT J
AU Charvet, CD
   Laird, J
   Xu, YF
   Salomon, RG
   Pikuleva, IA
AF Charvet, Casey D.
   Laird, James
   Xu, Yunfeng
   Salomon, Robert G.
   Pikuleva, Irina A.
TI Posttranslational modification by an isolevuglandin diminishes activity
   of the mitochondrial cytochrome P450 27A1
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE oxidative stress; multiple reaction monitoring; lipid peroxidation;
   gamma-ketoaldehydes; age-related macular degeneration; cholesterol
   metabolism; oxidative injury
ID RAT-LIVER MITOCHONDRIA; PROTEIN ADDUCTS; MASS-SPECTROMETRY; BILE-ACID;
   CEREBROTENDINOUS-XANTHOMATOSIS; STEROL 27-HYDROXYLASE;
   GAMMA-KETOALDEHYDES; ISOPROSTANE PATHWAY; CHOLESTEROL HOMEOSTASIS;
   MACULAR DEGENERATION
AB Posttranslational modification by isolevuglandins (isoLGs), arachidonate oxidation products, is an important yet understudied process associated with altered protein properties. This type of modification is detected in cytochrome P450 27A1 (CYP27A1), a multifunction enzyme expressed in almost every cell and involved in the metabolism of cholesterol and other sterols. Previously, the CYP27A1 Lys(358)-isoLG adduct was found in human retina afflicted with age-related macular degeneration. Yet, the effect of Lys(358) modification on enzyme activity was not investigated. Herein, we characterized catalytic properties of Lys(358) as well as Lys(476) CYP27A1 mutants before and after isoLG treatment and quantified the extent of modification by multiple reaction monitoring. The K358R mutant was less susceptible to isoLG-induced loss of catalytic activity than the wild type (WT), whereas the K476R mutant was nearly as vulnerable as the WT. Both mutants showed less isoLG modification than WT. Thus, modification of Lys(358), a residue involved in redox partner interactions, is the major contributor to isoLG-associated loss of CYP27A1 activity. Our data show the specificity of isoLG modification, provide direct evidence that isoLG adduction impairs enzyme activity, and support our hypothesis that isoLG modification in the retina is detrimental to CYP27A1 enzyme activity, potentially disrupting cholesterol homeostasis.-Charvet, C. D., J. Laird, Y. Xu, R. G. Salomon, and I. A. Pikuleva. Posttranslational modification by an isolevuglandin diminishes activity of the mitochondrial cytochrome P450 27A1. J. Lipid Res. 2013. 54: 1421-1429.
C1 [Charvet, Casey D.; Pikuleva, Irina A.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
   [Laird, James; Xu, Yunfeng; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
C3 Case Western Reserve University; Case Western Reserve University
RP Pikuleva, IA (通讯作者)，Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
EM iap8@case.edu
OI Salomon, Robert/0000-0001-9456-3557; Pikuleva, Irina/0000-0001-9742-6232
FU National Institutes of Health [EY-018383, GM-21249]; National Institutes
   of Health Training Grant Fellowship [T32 EY-007157]; Case Visual
   Sciences Research Center National Institutes of Health Core Grant [P30
   EY-11373]; NATIONAL EYE INSTITUTE [R01EY018383, P30EY011373,
   T32EY007157] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL
   MEDICAL SCIENCES [R01GM021249] Funding Source: NIH RePORTER
FX This work was supported in part by grants from the National Institutes
   of Health (EY-018383 to I.A.P. and GM-21249 to R.G.S.), a National
   Institutes of Health Training Grant Fellowship (T32 EY-007157 to C.D.C),
   and the Case Visual Sciences Research Center National Institutes of
   Health Core Grant (P30 EY-11373). I.A.P is a recipient of the Jules and
   Doris Stein Professorship from the Research to Prevent Blindness
   Foundation.
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NR 60
TC 15
Z9 15
U1 0
U2 17
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD MAY
PY 2013
VL 54
IS 5
BP 1421
EP 1429
DI 10.1194/jlr.M035790
PG 9
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 123MO
UT WOS:000317394300026
PM 23479405
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Miller, JW
   Le Couter, J
   Strauss, EC
   Ferrara, N
AF Miller, Joan W.
   Le Couter, Jennifer
   Strauss, Erich C.
   Ferrara, Napoleone
TI Vascular Endothelial Growth Factor A in Intraocular Vascular Disease
SO OPHTHALMOLOGY
LA English
DT Article
ID RETINAL VEIN OCCLUSION; DIABETIC-RETINOPATHY; MACULAR DEGENERATION;
   CHOROIDAL NEOVASCULARIZATION; VEGF-A; OCULAR NEOVASCULARIZATION; IRIS
   NEOVASCULARIZATION; PERMEABILITY FACTOR; NONHUMAN PRIMATE; AQUEOUS-HUMOR
AB The vascular beds supplying the retina may sustain injury as a result of underlying disease such as diabetes, and/or the interaction of genetic predisposition, environmental insults, and age. The vascular pathologic features observed in different intraocular vascular diseases can be categorized broadly as proliferation, exemplified by proliferative diabetic retinopathy, leakage such as macular edema secondary to retinal vein occlusion, or a combination of proliferation and leakage, as seen in neovascular age-related macular degeneration (AMD). The World Health Organization has identified diabetic retinopathy and AMD as priority eye diseases for the prevention of vision loss in developed countries. The pathologic transformations of the retinal vasculature seen in intraocular vascular disease are associated with increased expression of vascular endothelial growth factor A (VEGF), a potent endothelial-specific mitogen. Furthermore, in model systems, VEGF alone is sufficient to trigger intraocular neovascularization, and its inhibition is associated with functional and anatomic improvements in the affected eye. Therapeutic interventions with effect on VEGF include intraocular capture and neutralization by engineered antibodies or chimeric receptors, downregulation of its expression with steroids, or alleviation of retinal ischemia, a major stimulus for VEGF expression, with retinal ablation by laser treatment. Data from prospective randomized clinical trials indicate that VEGF inhibition is a potent therapeutic strategy for intraocular vascular disease. These findings are changing clinical practice and are stimuli for further study of the basic mechanisms controlling intraocular angiogenesis.
C1 [Miller, Joan W.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
   [Le Couter, Jennifer; Strauss, Erich C.; Ferrara, Napoleone] Genentech Inc, San Francisco, CA 94080 USA.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Roche Holding; Genentech
RP Miller, JW (通讯作者)，Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM Joan_Miller@meei.harvard.edu
OI Miller, Joan/0000-0003-2046-3996
FU Genentech, Inc., South San Francisco, California
FX Support for third-party writing and formatting assistance for this
   manuscript was provided by Ivo Stoilov, MD, CMPP, and was funded by
   Genentech, Inc., South San Francisco, California.
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NR 60
TC 279
Z9 294
U1 5
U2 85
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 2013
VL 120
IS 1
BP 106
EP 114
DI 10.1016/j.ophtha.2012.07.038
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 063PI
UT WOS:000313011700017
PM 23031671
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Heussen, FM
   Tan, CS
   Sadda, SR
AF Heussen, Florian M.
   Tan, Colin S.
   Sadda, SriniVas R.
TI Prevalence of Peripheral Abnormalities on Ultra-Widefield Greenlight
   (532 nm) Autofluorescence Imaging at a Tertiary Care Center
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID FUNDUS AUTOFLUORESCENCE; MYOPIA
AB METHODS. We conducted a retrospective review of cases seen at the Doheny Eye Institute between November 2009 and May 2011, who had ultra-widefield FAF and pseudocolor imaging performed on new models of scanning laser ophthalmoscopes. Patients with a history of previous therapies that could alter the FAF findings, including vitrectomy, cryotherapy, laser photocoagulation, or photodynamic therapy, were excluded from the analysis. Based on their primary diagnosis the eyes were grouped into nine disease categories: age-related macular degeneration, central serous retinopathy, dystrophy, inflammatory disorders, ocular tumor, retinal vascular disorders, other, normal, and unknown. All FAF and accompanying pseudocolor images were reviewed independently by two reading center-certified graders.
   RESULTS. A total of 470 eyes of 248 patients were included for analysis of which 461 eyes had images of sufficient quality for grading. The prevalence of peripheral findings was 65.5% (n = 302) for FAF images and 68.5% (n = 316) for the pseudocolor images (P < 0.001). The prevalence of peripheral abnormalities differed significantly between the disease categories ranging from 18.5% to 82.2% for FAF and 18.5% to 82.4% for pseudocolor images.
   CONCLUSIONS. Peripheral FAF abnormalities are frequent and readily revealed by FAF imaging. Interestingly, even cases with presumably macular disease demonstrated a high prevalence of peripheral findings. Further investigation in prospective studies is warranted. (Invest Ophthalmol Vis Sci. 2012;53:6526-6531) DOI:10.1167/iovs.12-9909
C1 [Heussen, Florian M.; Tan, Colin S.; Sadda, SriniVas R.] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA.
   [Heussen, Florian M.; Tan, Colin S.; Sadda, SriniVas R.] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
   [Heussen, Florian M.] Charite, Dept Ophthalmol, Campus Virchow Klinikum, D-13353 Berlin, Germany.
   [Tan, Colin S.] Natl Healthcare Grp Eye Inst, Singapore, Singapore.
   [Tan, Colin S.] Tan Tock Seng Hosp, Dept Ophthalmol, Singapore, Singapore.
C3 Doheny Eye Institute; University of Southern California; University of
   Southern California; Free University of Berlin; Humboldt University of
   Berlin; Charite Universitatsmedizin Berlin; Tan Tock Seng Hospital
RP Sadda, SR (通讯作者)，Univ So Calif, Keck Sch Med, Doheny Eye Inst, 1450 San Pablo St, Los Angeles, CA 90033 USA.
EM ssadda@doheny.org
RI Tan, Colin S/K-8972-2012
OI Tan, Colin S/0000-0003-3088-5690; Heussen, Florian
   Moritz/0000-0003-0536-9870
FU National Eye Institute/National Institutes of Health [EY03040, R01
   EY014375]; Deutsche Forschungsgemeinschaft [He 6094/1-1]; NATIONAL EYE
   INSTITUTE [P30EY003040, R01EY014375] Funding Source: NIH RePORTER
FX Supported in part by National Eye Institute/National Institutes of
   Health Grants EY03040 and R01 EY014375 and Deutsche
   Forschungsgemeinschaft Grant He 6094/1-1.
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NR 17
TC 38
Z9 40
U1 1
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 SEP
PY 2012
VL 53
IS 10
BP 6526
EP 6531
DI 10.1167/iovs.12-9909
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 016NQ
UT WOS:000309526200070
PM 22871828
OA Green Published
DA 2022-11-30
ER

PT J
AU Castro, JJ
   Jimenez, JR
   Ortiz, C
   Alarcon, A
   Anera, RG
AF Castro, Jose J.
   Jimenez, Jose R.
   Ortiz, Carolina
   Alarcon, Aixa
   Anera, Rosario G.
TI New testing software for quantifying discrimination capacity in subjects
   with ocular pathologies
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE discrimination capacity; disturbance index; retinal-image quality;
   Strehl ratio; keratitis; age-related macular degeneration
ID RETINAL-IMAGE QUALITY; WAVE-FRONT SENSOR; MACULAR DEGENERATION; VISUAL
   PERFORMANCE; CONTRAST SENSITIVITY; OPTICAL-QUALITY; HUMAN EYE;
   ABERRATIONS; KERATITIS; LASIK
AB We develop a new visual test, designed as software for quantifying discrimination capacity under low-illumination conditions. This is an important task in the presence of visual disturbances, such as those perceived by subjects with some ocular pathologies. For this purpose, we propose a visual-disturbance index, checking the test with two groups of observers having different ocular pathologies: a group with unilateral keratitis and another group affected with age-related macular degeneration (ARMD). To compare the test results to objective data, we use a double-pass device to measure the Strehl ratio, a parameter that quantifies the retinal-image quality, taking into account aberrations, retinal reflection, and intraocular scattering working jointly. Diseased eyes present higher disturbance indexes and a lower Strehl ratio compared to their healthy fellow eyes, registering a significant descending correlation between the disturbance index and the Strehl ratio. The lower the Strehl ratio is, the higher the disturbance index for the eyes studied. Therefore, in keratitis and ARMD eyes, our results demonstrate a deterioration in the retinal-image quality and a lower discrimination capacity to peripheral stimuli, reducing visual performance. The test presented here could be useful for the study and time course in different eye diseases, especially those involving an increase in scattered light or alterations in the ocular media, as shown in this work. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3526702]
C1 [Castro, Jose J.] Univ Granada, Fac Ciencias, Dept Opt, Lab Vis Sci & Applicat, E-18071 Granada, Spain.
C3 University of Granada
RP Castro, JJ (通讯作者)，Univ Granada, Fac Ciencias, Dept Opt, Lab Vis Sci & Applicat, Edificio Mecenas,Ave Fuentenueva S-N, E-18071 Granada, Spain.
EM jjcastro@ugr.es
RI Jimenez, Jose R/C-9362-2017; ORTIZ, CAROLINA/B-1280-2016; Ortiz,
   Carolina/ABE-8963-2020; Anera, Rosario G./L-4692-2017; Castro-Torres,
   José J./D-3828-2013
OI Jimenez, Jose R/0000-0002-0333-6883; ORTIZ,
   CAROLINA/0000-0003-0248-1699; Ortiz, Carolina/0000-0003-0248-1699;
   Anera, Rosario G./0000-0003-3614-2142; Castro-Torres, José
   J./0000-0003-0461-925X
FU Ministerio de Educacion y Ciencia (Spain) [FIS2009-07482]; Junta de
   Andalucia (Spain) [P06-FQM-01359]
FX We thank David Nesbitt for translating the text into English. This
   research was supported by the Ministerio de Educacion y Ciencia (Spain)
   Grant No. FIS2009-07482 and Junta de Andalucia (Spain) Grant No.
   P06-FQM-01359.
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NR 23
TC 37
Z9 38
U1 0
U2 5
PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD JAN
PY 2011
VL 16
IS 1
AR 015001
DI 10.1117/1.3526702
PG 7
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 725HW
UT WOS:000287636800015
PM 21280903
OA Bronze
DA 2022-11-30
ER

PT J
AU Krohne, TU
   Stratmann, NK
   Kopitz, J
   Holz, FG
AF Krohne, Tim U.
   Stratmann, Nina K.
   Kopitz, Juergen
   Holz, Frank G.
TI Effects of lipid peroxidation products on lipofuscinogenesis and
   autophagy in human retinal pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; retinal pigment epithelium;
   lipofuscin, autophagy; lysosome; outer segments; oxidative damage; lipid
   peroxidation
ID FUNDUS AUTOFLUORESCENCE PATTERNS; PHOTORECEPTOR OUTER SEGMENTS; HUMAN
   RPE CELLS; MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; LYSOSOMAL FUNCTION;
   VISUAL IMPAIRMENT; UNITED-STATES; PATHOGENESIS; DISEASE
AB Several lines of evidence suggest that progressive dysfunction of the retinal pigment epithelium (RPE) is central to the pathogenesis of age-related macular degeneration (AMD). We previously demonstrated that protein modifications with lipid peroxidation products, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), induce lysosomal dysfunction in RPE cells in vitro. Here, we investigated whether phagocytosis of modified photoreceptor outer segments (POS) affects lipofuscinogenesis and autophagy, two interrelated processes directly connected to lysosomal function. Incubation of human RPE cells with HNE- and MDA-modified POS resulted in pronounced intracellular accumulation of granular material with lipofuscin-like autofluorescence. After daily treatment with modified POS for 7 days, cellular autofluorescence increased 8.2-fold as quantified by flow cytometry. In the presence of the lysosomal inhibitor ammonium chloride, unmodified POS likewise induced an 8.0-fold increase in autofluorescence. Spectral profiles of cellular autofluorescence after incubation with modified POS were unchanged compared to incubation with native POS. Autophagy activity, measured as turnover of metabolically radiolabeled endogenous proteins, was reduced by both HNE- and MDA-modified POS by 40%. Autophagy inhibition by 3-methyladenine and lysosomal inhibition by ammonium chloride induced lipofuscinogenesis even in the absence of POS. In summary, our results demonstrate that induction of lysosomal dysfunction by lipid peroxidation-derived protein modifications results in increased lipofuscinogenesis and reduced autophagy activity in RPE cells in vitro. These mechanisms may contribute to RPE cell dysfunction and degeneration in AMD. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Krohne, Tim U.; Stratmann, Nina K.; Holz, Frank G.] Univ Bonn, Dept Ophthalmol, D-5300 Bonn, Germany.
   [Kopitz, Juergen] Univ Heidelberg, Dept Mol Pathol, Heidelberg, Germany.
C3 University of Bonn; Ruprecht Karls University Heidelberg
RP Krohne, TU (通讯作者)，Univ Eye Hosp, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM krohne@uni-bonn.de
RI Krohne, Tim/D-1497-2013; Krohne, Tim/AAG-4412-2020
OI Krohne, Tim/0000-0003-2280-925X; 
FU German Research Foundation (DFG) [KR 2863/6-1, SPP 1088, HO 1926/2-1
   UK]; University of Bonn BONFOR Program; Gerok Fellowship; German
   Ophthalmological Society (DOG); Alcon Retina Scholarship; Dr. Eberhard
   and Hilde Rudiger Foundation
FX The authors thank Claudine Strack, BTA, and Sigrun Himmelsbach, MTA, for
   expert technical assistance.; This study was supported by the German
   Research Foundation (DFG), grant KR 2863/6-1 (TUK); DFG Priority Program
   "Age-related macular degeneration" (SPP 1088), grant HO 1926/2-1 UK,
   FGH); University of Bonn BONFOR Program, Gerok Fellowship (TUK); the
   German Ophthalmological Society (DOG), Alcon Retina Scholarship (TUK);
   and the Dr. Eberhard and Hilde Rudiger Foundation (TUK).
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NR 54
TC 107
Z9 111
U1 0
U2 15
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAR
PY 2010
VL 90
IS 3
BP 465
EP 471
DI 10.1016/j.exer.2009.12.011
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 572QO
UT WOS:000275848100014
PM 20059996
DA 2022-11-30
ER

PT J
AU Mandal, NA
   Ayyagari, R
AF Mandal, Nawajes A.
   Ayyagari, Radha
TI Complement factor H: Spatial and temporal expression and localization in
   the eye
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; HOMOZYGOUS FACTOR-H; MACULAR DEGENERATION;
   MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; DEPOSIT DISEASE; PROTEIN
   BETA-1H; C3B INACTIVATOR; GENE MUTATION; DEFICIENCY; DRUSEN
AB PURPOSE. Complement factor H (CFH) is a component of the mammalian complement system, which regulates the alternative pathway of complement activation and protects the host cell from inappropriate complement activation. CFH is a key regulator of innate immunity, and CFH deficiency leads to membranoproliferative glomerulonephritis type II. A variation in human CFH, Y402H, has been shown to be associated with an increased risk for age-related macular degeneration. The authors describe studies on the spatial and temporal expression of the CFH gene and localization of this protein in ocular tissues to gain insight into its role in the eye.
   METHODS. CFH expression in human and mouse tissues was studied by quantitative RT-PCR and Western blot analysis, and localization of CFH was studied by immunohistochemical analysis followed by fluorescence microscopy.
   RESULTS. In human and mouse, CFH expression was found to be similar to the highest level of expression in the liver. In ocular tissue, CFH was detected in the distalmost optic nerve (3 mm) cut from the scleral surface of the eyeball, sclera, RPE-choroid, retina, lens, and ciliary body. In mouse, Cfh expression was observed from early embryonic stages, and in the eye its expression increased with age.
   CONCLUSIONS. A significant level of CFH expression is maintained in different ocular tissues during development and aging. Sustained high levels of CFH expression in eye tissues suggest that this protein may play a role in protecting these tissues from indiscriminate complement activation and inflammatory insult.
C1 Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
C3 University of Michigan System; University of Michigan
RP Ayyagari, R (通讯作者)，Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM ayyagari@umich.edu
FU NATIONAL EYE INSTITUTE [R01EY013198] Funding Source: NIH RePORTER; NEI
   NIH HHS [EY07003, EY07060, EY13198] Funding Source: Medline
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NR 47
TC 62
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
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD SEP
PY 2006
VL 47
IS 9
BP 4091
EP 4097
DI 10.1167/iovs.05-1655
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 077SP
UT WOS:000240050700056
PM 16936129
DA 2022-11-30
ER

PT J
AU Kymes, SM
   Walline, JJ
   Zadnik, K
   Gordon, MO
AF Kymes, SM
   Walline, JJ
   Zadnik, K
   Gordon, MO
CA CLEK Study Grp
TI Quality of life in Keratoconus
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID VISUAL FUNCTION QUESTIONNAIRE; HEALTH-STATUS; DISEASE
AB PURPOSE: Keratoconus is a chronic, noninflammatory disease of the cornea with onset in early adulthood. As these years are important to financial and social health, keratoconus may have more severe impact on quality of life than would be expected given its clinical severity. We examined the vision-related quality of life of patients in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study.
   DESIGN: Cross-sectional study.
   METHODS: The National Eye Institute,Visual Function Questionnaire (NEI-VFQ) was administered to 1166 CLEK Study patients at their first annual follow,up examination. Associations between clinical and demographic factors and NEI-VFQ scale scores were evaluated.
   RESULTS: Binocular entrance visual acuity worse than 20/40 was associated with lower quality of life scores on all scales except General Health and Ocular Pain. A steep keratometric reading (average of both eyes) >52 diopters (D) was associated with lower scores on the Mental Health, Role Difficulty, Driving, Dependency, and Ocular Pain scales. Scores for CLEK patients on all scales were between patients with category 3 and category 4 age-related macular degeneration (AMD) except General Health, which was better than AMD patients, and Ocular Pain, which was worse than AMD patients.
   CONCLUSIONS: Keratoconus is a disease of relatively low prevalence that rarely results in blindness, but because it affects young adults, the magnitude of its public health impact is disproportionate to its prevalence and clinical severity. (C) 2004 by Elsevier Inc. All rights reserved.
C1 Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
   Ohio State Univ, Coll Optometry, Columbus, OH 43210 USA.
C3 Washington University (WUSTL); University System of Ohio; Ohio State
   University
RP Kymes, SM (通讯作者)，Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, Campus Box 8096,660 S Euclid Ave, St Louis, MO 63110 USA.
EM kymes@vrcc.wustl.edu
RI , Jeff/AAE-1426-2022
OI , Jeff/0000-0002-9503-6094
FU NATIONAL EYE INSTITUTE [P30EY002687, U10EY010077, U10EY010069,
   U10EY010419, U10EY012656] Funding Source: NIH RePORTER; NEI NIH HHS
   [EY02687, EY10069, EY10419, EY12656, EY10077] Funding Source: Medline
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NR 27
TC 153
Z9 157
U1 2
U2 19
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 OCT
PY 2004
VL 138
IS 4
BP 527
EP 535
DI 10.1016/j.ajo.2004.04.031
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 864UO
UT WOS:000224658600002
PM 15488776
DA 2022-11-30
ER

PT J
AU Gu, XR
   Sun, MJ
   Gugiu, B
   Hazen, S
   Crabb, JW
   Salomon, RG
AF Gu, XR
   Sun, MJ
   Gugiu, B
   Hazen, S
   Crabb, JW
   Salomon, RG
TI Oxidatively truncated docosahexaenoate phospholipids: Total synthesis,
   generation, and peptide adduction chemistry
SO JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; SCAVENGER RECEPTOR CD36; OXIDIZED
   PHOSPHOLIPIDS; MACULAR DEGENERATION; 2-LYSOPHOSPHATIDYLCHOLINE;
   IDENTIFICATION; PRODUCTS; ESTERS; LIPIDS; FAMILY
AB The recent immunological detection of extraordinarily high levels of carboxyethylpyrrole (CEP) modifications of proteins from the retinas of individuals with age-related macular degeneration provided presumptive evidence for the involvement of docosahexaenoate-derived oxidatively truncated phospholipids in retinal pathology. To facilitate the in vivo detection and characterization of the chemistry and biological activities of these postulated naturally occurring molecules, a family of oxidatively truncated phospholipids was prepared by total syntheses. Their formation in oxidation reactions of a docosahexaenoate ester of 2-lysophosphatidylcholine (DHA-PC) was also demonstrated. Free radical-induced oxidative cleavage of DHA-PC promoted by myeloperoxidase or copper ions generates similar mixtures of these phospholipids. The most abundant products were 1-palmitoyl-2-succinoyl-sn-glycero-3-phosphatidylcholine (4.7%) and 2-(6-carboxy-4-oxohex-5-enoyl)-1-palmitoylsn-glycero-3-phosphatidylcholine (1.7%). Both of these oxidatively truncated phospholipids are homologues of biologically active arachidonate-derived phospholipids. A minor product from DHA-PC, 2-(4-hydroxy-7-oxohept-5-enoyl)-1-palmitoyl-sn-glycero-3-phosphatidylcholine (0.4% yield), reacted with the 6-amino group of a peptide lysyl residue to produce a CEP derivative in 0.7% yield. These observations support the previous conclusion, based on immunological evidence, that CEPs are generated by the reaction of an oxidatively truncated phospholipid with proteins in the retina and further indicate that CEP protein modifications probably represent only a tiny fraction of the products generated upon oxidative damage of DHA-PC in photoreceptor disk membranes.
C1 Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
   Cleveland Clin Fdn, Dept Cell Biol, Cleveland, OH 44195 USA.
   Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA.
C3 Cleveland Clinic Foundation; Cleveland Clinic Foundation; Cleveland
   Clinic Foundation
RP Salomon, RG (通讯作者)，Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
EM rgs@po.cwru.edu
RI Hazen, Stanley L/ABD-5845-2021; Salomon, Robert G/C-3463-2008
OI Salomon, Robert/0000-0001-9456-3557
FU NEI NIH HHS [EY014239, EY06603] Funding Source: Medline; NHLBI NIH HHS
   [HL70621] Funding Source: Medline; NIGMS NIH HHS [GM21249] Funding
   Source: Medline; NATIONAL EYE INSTITUTE [R01EY014239] Funding Source:
   NIH RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL070621]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL
   SCIENCES [R01GM021249] Funding Source: NIH RePORTER
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NR 37
TC 64
Z9 67
U1 0
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-3263
J9 J ORG CHEM
JI J. Org. Chem.
PD MAY 16
PY 2003
VL 68
IS 10
BP 3749
EP 3761
DI 10.1021/jo026721t
PG 13
WC Chemistry, Organic
WE Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)
SC Chemistry
GA 677UA
UT WOS:000182825000002
PM 12737551
DA 2022-11-30
ER

PT J
AU Uemura, A
   Fruttiger, M
   D'Amore, PA
   De Falco, S
   Joussen, AM
   Sennlaub, F
   Brunck, LR
   Johnson, KT
   Lambrou, GN
   Rittenhouse, KD
   Langmann, T
AF Uemura, Akiyoshi
   Fruttiger, Marcus
   D'Amore, Patricia A.
   De Falco, Sandro
   Joussen, Antonia M.
   Sennlaub, Florian
   Brunck, Lynne R.
   Johnson, Kristian T.
   Lambrou, George N.
   Rittenhouse, Kay D.
   Langmann, Thomas
TI VEGFR1 signaling in retinal angiogenesis and microinflammation
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Angiogenesis; Microinflammation; Placental growth factor (PlGF);
   Vascular endothelial growth factor-A (VEGF-A); Vascular endothelial
   growth factor receptor 1; (VEGFR1)
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC MACULAR EDEMA; VASCULAR-PERMEABILITY
   FACTOR; NITRIC-OXIDE SYNTHASE; SINGLE INTRAVITREAL INJECTION;
   OXYGEN-INDUCED RETINOPATHY; MESSENGER-RNA STABILITY; BRANCH VEIN
   OCCLUSION; HIGH-AFFINITY BINDING; AQUEOUS-HUMOR LEVELS
AB Five vascular endothelial growth factor receptor (VEGFR) ligands (VEGF-A, -B, -C, -D, and placental growth factor [PlGF]) constitute the VEGF family. VEGF-A binds VEGF receptors 1 and 2 (VEGFR1/2), whereas VEGF-B and PlGF only bind VEGFR1. Although much research has been conducted on VEGFR2 to elucidate its key role in retinal diseases, recent efforts have shown the importance and involvement of VEGFR1 and its family of ligands in angiogenesis, vascular permeability, and microinflammatory cascades within the retina. Expression of VEGFR1 depends on the microenvironment, is differentially regulated under hypoxic and inflammatory conditions, and it has been detected in retinal and choroidal endothelial cells, pericytes, retinal and choroidal mononuclear phagocytes (including microglia), Muller cells, photoreceptor cells, and the retinal pigment epithelium. Whilst the VEGF-A decoy function of VEGFR1 is well established, consequences of its direct signaling are less clear. VEGFR1 activation can affect vascular permeability and induce macrophage and microglia production of proinflammatory and proangiogenic mediators. However the ability of the VEGFR1 ligands (VEGF-A, PlGF, and VEGF-B) to compete against each other for receptor binding and to heterodimerize complicates our understanding of the relative contribution of VEGFR1 signaling alone toward the pathologic processes seen in diabetic retinopathy, retinal vascular occlusions, retinopathy of prematurity, and age-related macular degeneration. Clinically, anti-VEGF drugs have proven transformational in these pathologies and their impact on modulation of VEGFR1 signaling is still an opportunity-rich field for further research.
C1 [Uemura, Akiyoshi] Nagoya City Univ, Grad Sch Med Sci, Dept Retinal Vasc Biol, Mizuho Ku, 1 Kawasumi Mizuho Cho, Nagoya, Aichi 4678601, Japan.
   [Fruttiger, Marcus] UCL, UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
   [D'Amore, Patricia A.] Massachusetts Eye & Ear, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
   [De Falco, Sandro] Inst Genet & Biophys Adriano Buzzati Traverso, Angiogenesis Lab, Via Pietro Castellino 111, I-80131 Naples, Italy.
   [De Falco, Sandro] ANBITION Srl, Via Manzoni 1, I-80123 Naples, Italy.
   [Joussen, Antonia M.] Charite Univ Med Berlin, Dept Ophthalmol, Hindenburgdamm 30, D-12200 Berlin, Germany.
   [Joussen, Antonia M.] Augustenburger Pl 1, D-13353 Berlin, Germany.
   [Sennlaub, Florian] Sorbonne Univ, INSERM, CNRS, Inst Vis, 17 Rue Moreau, F-75012 Paris, France.
   [Brunck, Lynne R.; Johnson, Kristian T.; Lambrou, George N.; Rittenhouse, Kay D.] Bayer Consumer Care AG, Pharmaceut, Peter Merian Str 84, CH-4052 Basel, Switzerland.
   [Langmann, Thomas] Univ Cologne, Lab Expt Immunol Eye, Dept Ophthalmol, Fac Med, Joseph Stelzmann Str 9, D-50931 Cologne, Germany.
   [Langmann, Thomas] Univ Cologne, Univ Hosp Cologne, Joseph Stelzmann Str 9, D-50931 Cologne, Germany.
C3 Nagoya City University; University of London; University College London;
   Harvard University; Massachusetts Eye & Ear Infirmary; Schepens Eye
   Research Institute; Consiglio Nazionale delle Ricerche (CNR); Istituto
   di Genetica e Biofisica "Adriano Buzzati-Traverso" (IGB-CNR); Free
   University of Berlin; Humboldt University of Berlin; Charite
   Universitatsmedizin Berlin; Centre National de la Recherche Scientifique
   (CNRS); Institut National de la Sante et de la Recherche Medicale
   (Inserm); UDICE-French Research Universities; Sorbonne Universite;
   Universite Paris Cite; Bayer AG; University of Cologne; University of
   Cologne
RP Fruttiger, M (通讯作者)，UCL, UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
EM uemura@med.nagoya-cu.ac.jp; m.fruttiger@ucl.ac.uk;
   patricia_damore@meei.harvard.edu; sandro.defalco@igb.cnr.it;
   antonia.Joussen@charite.de; florian.sennlaub@gmail.com;
   lynne.brunck@bayer.com; kristian.johnson@bayer.com;
   george.lambrou@bayer.com; kay.rittenhouse@bayer.com;
   thomas.langmann@uk-koeln.de
RI Joussen, Antonia/AAA-6901-2022; Uemura, Akiyoshi/I-7510-2017
OI Fruttiger, Marcus/0000-0002-6962-5485; Uemura,
   Akiyoshi/0000-0001-5574-5470; De Falco, Sandro/0000-0002-6501-1697
FU Bayer Consumer Care AG (Switzerland)
FX Medical writing, illustration, and editorial assistance (under the
   direction of the authors) was provided by Apothecom, UK, and funded by
   Bayer Consumer Care AG (Switzerland) .
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NR 400
TC 27
Z9 28
U1 9
U2 25
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 2021
VL 84
AR 100954
DI 10.1016/j.preteyeres.2021.100954
EA SEP 2021
PG 24
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UR8XL
UT WOS:000697024800002
PM 33640465
OA Green Accepted, Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Ma, N
   Yang, XL
   Qi, C
   Yu, QL
   Zhu, C
   Ren, H
AF Ma, Ning
   Yang, Xiaolin
   Qi, Chong
   Yu, Qinlei
   Zhu, Chao
   Ren, Hua
TI Farrerol Enhances Nrf2-Mediated Defense Mechanisms against Hydrogen
   Peroxide-Induced Oxidative Damage in Human Retinal Pigment Epithelial
   Cells by Activating Akt and MAPK
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
AB Oxidative stress of the retinal pigment epithelium (RPE) is an essential element contributing to the progression of age-related macular degeneration (AMD). Notably, the activation of Nrf2 is regarded as an effective strategy for controlling oxidation. The novel 2,3-dihydroflavonoid compound farrerol, which is extracted from Rhododendron, possesses antioxidant properties. In this study, we investigated the mechanism by which farrerol protects against oxidative damage mediated by hydrogen peroxide (H2O2) in adult retinal pigment epithelial cell line 19 (ARPE-19) cells. Farrerol supplementation conspicuously reversed H2O2-related cell damage through declining the generation of intracellular reactive oxygen species (ROS) and MDA and increasing the concentrations of GSH and SOD. According to the results of the apoptosis assay, a farrerol pretreatment decreased the protein expression of the Bax/Bcl-2, cleaved caspase-3, PARP, caspase-8, and caspase-9 proteins. Furthermore, farrerol markedly activated Nrf2, thereby increasing the levels of antioxidant enzymes downstream of Nrf2, such as HO-1, NQO1, and GCLM. Knockdown of Nrf2 with a specific siRNA successfully suppressed farrerol-mediated HO-1 transcription and partially abolished the cytoprotective effect on ARPE-19 cells. Meanwhile, farrerol induced Akt and MAPK phosphorylation in a dose-related way. However, inhibiting Akt and MAPK substantially blocked the cytoprotective functions of farrerol. Therefore, farrerol enhanced Nrf2-mediated cytoprotection of oxidative damage caused by H2O2, which may be inseparable from the activation of Akt and MAPK.
C1 [Ma, Ning; Ren, Hua] First Hosp Jilin Univ, Dept Ophthalmol, Changchun 130001, Peoples R China.
   [Yang, Xiaolin] First Hosp Jilin Univ, Dept Geriatr, Changchun, Peoples R China.
   [Qi, Chong] First Hosp Jilin Univ, Inst Translat Med, Changchun, Peoples R China.
   [Yu, Qinlei] Jilin Prov Anim Dis Control Ctr, 4510 Xian Rd, Changchun 130062, Peoples R China.
   [Zhu, Chao] Second Hosp Jilin Univ, Dept Ophthalmol, Changchun 130041, Peoples R China.
C3 Jilin University; Jilin University; Jilin University; Jilin University
RP Ren, H (通讯作者)，First Hosp Jilin Univ, Dept Ophthalmol, Changchun 130001, Peoples R China.
EM 839991212@qq.com; 359673426@qq.com; 15450773@qq.com; 158703012@qq.com;
   cz3531@163.com; 2530548289@qq.com
OI Yang, Xiaolin/0000-0002-4110-4805; Qi, Chong/0000-0003-1152-9746; Ma,
   Ning/0000-0002-0196-988X; yu, qinlei/0000-0003-2194-3043; Zhu,
   Chao/0000-0002-1271-5500; Ren, Hua/0000-0002-6712-4556
FU National Science Foundation of China [81700860]; Natural Science
   Foundation of Jilin Province [20180101288JC]
FX This work was in part supported by the National Science Foundation of
   China (Grant No. 81700860) and the Natural Science Foundation of Jilin
   Province (Grant No. 20180101288JC).
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NR 38
TC 5
Z9 6
U1 4
U2 7
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 MAR 4
PY 2021
VL 2021
AR 8847844
DI 10.1155/2021/8847844
PG 13
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA QX5CL
UT WOS:000629364100005
PM 33763175
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Xu, Y
   Cui, KX
   Li, J
   Tang, XY
   Lin, JQ
   Lu, X
   Huang, R
   Yang, BY
   Shi, YX
   Ye, D
   Huang, JJ
   Yu, SS
   Liang, XL
AF Xu, Yue
   Cui, Kaixuan
   Li, Jia
   Tang, Xiaoyu
   Lin, Jianqiang
   Lu, Xi
   Huang, Rong
   Yang, Boyu
   Shi, Yuxun
   Ye, Dan
   Huang, Jingjing
   Yu, Shanshan
   Liang, Xiaoling
TI Melatonin attenuates choroidal neovascularization by regulating
   macrophage/microglia polarization via inhibition of RhoA/ROCK signaling
   pathway
SO JOURNAL OF PINEAL RESEARCH
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization;
   macrophage; melatonin; microglia; polarization; RhoA; ROCK signaling
   pathway
ID MACULAR DEGENERATION; OXIDATIVE STRESS; MACROPHAGES; PHYSIOLOGY; MODEL;
   ANGIOGENESIS; INFLAMMATION; EXPRESSION; DYNAMICS; RETINA
AB Choroidal neovascularization (CNV) is an important characteristic of advanced wet age-related macular degeneration (AMD) and leads to severe visual impairment among elderly patients. Previous studies have demonstrated that melatonin induces several biological effects related to antioxidation, anti-inflammation, and anti-angiogenesis. However, the role of melatonin in CNV, and its underlying mechanisms, has not been investigated thus far. In this study, we found that melatonin administration significantly reduced the scale and volume of CNV lesions, suppressed vascular leakage, and inhibited the capacity of vascular proliferation in the laser-induced mouse CNV model. Additionally, the results also show that the melatonin-treated retinal microglia in the laser-induced mice exhibited enhanced expression of M1-type markers, such as iNOS, CCL-3, CCL-5, and TNF-alpha, as well as decreased production of M2-type markers, such as Arg-1, Fizz-1, IL-10, YM-1, and CD206, indicating that melatonin switched the macrophage/microglia polarization from pro-angiogenic M2 phenotype to anti-angiogenic M1 phenotype. Furthermore, the RhoA/ROCK signaling pathway was activated during CNV formation, yet was suppressed after an intraperitoneal injection of melatonin. In conclusion, melatonin attenuated CNV, reduced vascular leakage, and inhibited vascular proliferation by switching the macrophage/microglia polarization from M2 phenotype to M1 phenotype via inhibition of RhoA/ROCK signaling pathway in CNV. This suggests that melatonin could be a novel agent for the treatment of AMD.
C1 [Xu, Yue; Cui, Kaixuan; Li, Jia; Tang, Xiaoyu; Lin, Jianqiang; Lu, Xi; Huang, Rong; Yang, Boyu; Shi, Yuxun; Ye, Dan; Huang, Jingjing; Yu, Shanshan; Liang, Xiaoling] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou, Guangdong, Peoples R China.
C3 Sun Yat Sen University
RP Yu, SS; Liang, XL (通讯作者)，Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou, Guangdong, Peoples R China.
EM sherior_yu@163.com; liangxlsums@qq.com
RI yu, shanshan/AIC-2220-2022
OI yu, shanshan/0000-0001-6182-8328; Lin, Jianqiang/0000-0001-5651-1932
FU National Natural Science Foundation of China [81870668]; Young
   Scientists Fund of the National Natural Science Foundation of China
   [81900864]
FX National Natural Science Foundation of China, Grant/Award Number: No.
   81870668; Young Scientists Fund of the National Natural Science
   Foundation of China, Grant/Award Number: No. 81900864
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NR 59
TC 50
Z9 55
U1 6
U2 31
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0742-3098
EI 1600-079X
J9 J PINEAL RES
JI J. Pineal Res.
PD AUG
PY 2020
VL 69
IS 1
AR e12660
DI 10.1111/jpi.12660
EA MAY 2020
PG 20
WC Endocrinology & Metabolism; Neurosciences; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Endocrinology & Metabolism; Neurosciences & Neurology; Physiology
GA MU8YU
UT WOS:000532850800001
PM 32323368
DA 2022-11-30
ER

PT J
AU Liu, JX
   Li, S
   Li, G
   Li, X
   Yu, CH
   Fu, ZJ
   Li, XY
   Teng, LS
   Li, YX
   Sun, FY
AF Liu, Jiaxin
   Li, Shuang
   Li, Ge
   Li, Xiang
   Yu, Changhui
   Fu, Zhijiang
   Li, Xiangyu
   Teng, Lesheng
   Li, Youxin
   Sun, Fengying
TI Highly bioactive, bevacizumab-loaded, sustained-release PLGA/PCADK
   microspheres for intravitreal therapy in ocular diseases
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE Microspheres; PCADK; PLGA; Bevacizumab; AMD
ID MACULAR DEGENERATION; PLGA NANOPARTICLES; STABILITY; AVASTIN
AB Bevacizumab, a vascular endothelial growth factor (VEGF)-targeting drug, is widely used as an off-label therapeutic for age-related macular degeneration (AMD). To reduce the monthly administration frequency, this study investigated microspheres comprising a poly(D, L-lactide-co-glycolide)/poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PLGA/PCADK) blend that could be loaded with bevacizumab-dextran particles using solid-in-oil-in-water (S/O/W) emulsification. Control microspheres were also prepared through water-in-oil-in-water (W/O/W) emulsification. The structural stability of bevacizumab in the polymer monomers was analyzed using dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size exclusion chromatography (SEC-HPLC), circular dichroism (CD) and fluorescence spectroscopy. Subsequently, microspheres were prepared and evaluated in terms of their morphology, encapsulation efficiency and release behavior. PLGA/PCADK microspheres prepared by the S/O/W method with < 20% PCADK showed a smooth spherical structure with a uniform distribution of bevacizumab. The microspheres exhibited a release behavior comprising a slight initial burst and an increasing total release over 50 days both in vitro and in vivo. Additionally, the microspheres were well tolerated by ocular tissue. Finally, a chorioallantoic membrane (CAM) assay revealed that the bioactivity of bevacizumab was retained by PCADK. In conclusion, these results suggest the potential for bevacizumab-loaded PLGA/PCADK microspheres prepared by the S/O/W method as a means of intravitreal therapy for ocular diseases.
C1 [Liu, Jiaxin; Li, Shuang; Li, Ge; Yu, Changhui; Fu, Zhijiang; Li, Xiangyu; Teng, Lesheng; Li, Youxin; Sun, Fengying] Jilin Univ, Sch Life Sci, Changchun 130012, Jilin, Peoples R China.
   [Li, Xiang; Li, Youxin] Shandong Luye Pharmaceut Co Ltd, State Key Lab Long Acting & Targeting Drug Delive, Yantai 264003, Shandong, Peoples R China.
C3 Jilin University
RP Li, YX; Sun, FY (通讯作者)，Jilin Univ, Sch Life Sci, Changchun 130012, Jilin, Peoples R China.; Li, YX (通讯作者)，Shandong Luye Pharmaceut Co Ltd, State Key Lab Long Acting & Targeting Drug Delive, Yantai 264003, Shandong, Peoples R China.
EM liyouxin@jlu.edu.cn; sunfengying@jlu.edu.cn
RI Fu, Zhijiang/Y-4287-2019; Li, Xiangyu/GXG-4002-2022
OI Liu, Jiaxin/0000-0002-8770-2093; Li, Shuang/0000-0001-9853-5035; Teng,
   Lesheng/0000-0003-1623-5384
FU Jilin Province Science and Technology Development Program
   [20180101269JC]; State Key Laboratory of Long-Acting and Targeting Drug
   Delivery System; Shandong Luye Pharmaceutical Co., Ltd.
FX This research was supported by the Jilin Province Science and Technology
   Development Program (No. 20180101269JC) and the State Key Laboratory of
   Long-Acting and Targeting Drug Delivery System and Shandong Luye
   Pharmaceutical Co., Ltd.
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NR 27
TC 18
Z9 18
U1 2
U2 56
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5173
EI 1873-3476
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD MAY 30
PY 2019
VL 563
BP 228
EP 236
DI 10.1016/j.ijpharm.2019.04.012
PG 9
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA HV7FH
UT WOS:000466146400022
PM 30959236
OA hybrid
DA 2022-11-30
ER

PT J
AU Farjood, F
   Vargis, E
AF Farjood, Farhad
   Vargis, Elizabeth
TI Novel devices for studying acute and chronic mechanical stress in
   retinal pigment epithelial cells
SO LAB ON A CHIP
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; OPTICAL COHERENCE TOMOGRAPHY; AGE-RELATED
   MACULOPATHY; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; FACTOR
   VEGF; DIFFERENTIAL EXPRESSION; VASCULAR-PERMEABILITY; BEVACIZUMAB
   TREATMENT; OXIDATIVE STRESS
AB Choroidal neovascularization (CNV) is a major cause of blindness in patients with age-related macular degeneration (AMD). Overexpression of vascular endothelial growth factor (VEGF), a potent angiogenic protein, by retinal pigment epithelial (RPE) cells is a key stimulator of CNV. Mechanical stress occurs during different stages of AMD and is a possible inducer of VEGF expression in RPE cells. However, robust and realistic approaches to studying acute and chronic mechanical stress under various AMD stages do not exist. The majority of previous work has studied cyclic stretching of RPE cells grown on flexible substrates, but an ideal model must be able to mimic localized and continuous stretching of the RPE as would occur in AMD in vivo. To bridge this gap, we developed two in vitro devices to model chronic and acute mechanical stress on RPE cells during different stages of AMD. In one device, high levels of continuous mechanical stress were applied to focal regions of the RPE monolayer by stretching the underlying silicon substrate to study the role of chronic mechanical stimulation. In the second device, RPE cells were grown on porous plastic substrates and acute stress was studied by stretching small areas. Using these devices, we studied the effect of mechanical stress on VEGF expression in RPE cells. Our results suggest that mechanical stress in RPE cells induces VEGF expression and promotes in vitro angiogenesis. These results confirm the hypothesis that mechanical stress is involved in the initiation and progression of CNV.
C1 [Farjood, Farhad; Vargis, Elizabeth] Utah State Univ, Dept Biol Engn, 4105 Old Main Hill, Logan, UT 84322 USA.
C3 Utah System of Higher Education; Utah State University
RP Vargis, E (通讯作者)，Utah State Univ, Dept Biol Engn, 4105 Old Main Hill, Logan, UT 84322 USA.
EM vargis@usu.edu
FU Knights Templar Eye Foundation; Ralph E. Powe Junior Faculty Award from
   the Oak Ridge Associated Universities (ORAU); Utah State University's
   Office of Research and Graduate Studies; Utah State University's College
   of Engineering
FX The authors thank Lori Caldwell, Cynthia Hanson and Charles Harding for
   their assistance in editing the manuscript. This work was supported by a
   Career Starter Grant from the Knights Templar Eye Foundation, a Ralph E.
   Powe Junior Faculty Award from the Oak Ridge Associated Universities
   (ORAU), Utah State University's Office of Research and Graduate Studies,
   and Utah State University's College of Engineering.
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NR 84
TC 10
Z9 10
U1 0
U2 10
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
   ENGLAND
SN 1473-0197
EI 1473-0189
J9 LAB CHIP
JI Lab Chip
PD NOV 21
PY 2018
VL 18
IS 22
BP 3413
EP 3424
DI 10.1039/c8lc00659h
PG 12
WC Biochemical Research Methods; Chemistry, Multidisciplinary; Chemistry,
   Analytical; Nanoscience & Nanotechnology; Instruments & Instrumentation
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry; Science & Technology -
   Other Topics; Instruments & Instrumentation
GA GZ4WX
UT WOS:000449411200008
PM 30328441
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Sesar, A
   Cavar, I
   Sesar, AP
   Geber, MZ
   Sesar, I
   Laus, KN
   Vatavuk, Z
   Mandic, Z
AF Sesar, Antonio
   Cavar, Ivan
   Sesar, Anita Pusic
   Geber, Mia Zoric
   Sesar, Irena
   Laus, Katia Novak
   Vatavuk, Zoran
   Mandic, Zdravko
TI Macular Thickness after Glaucoma Filtration Surgery
SO COLLEGIUM ANTROPOLOGICUM
LA English
DT Article
DE macular thickness; glaucoma; trabeculectomy; optical coherence
   tomography; intaocular pressure; starling forces
ID OPTICAL COHERENCE TOMOGRAPHY; BLOOD-AQUEOUS BARRIER; EXTRACAPSULAR
   CATARACT-EXTRACTION; HYPOTONY MACULOPATHY; UNCOMPLICATED
   PHACOEMULSIFICATION; POSTOPERATIVE HYPOTONY; INTRAOCULAR-PRESSURE;
   VISUAL-ACUITY; EDEMA; OCT
AB The aim of present study was to analyze early postoperative changes in the macular area using optical coherence tomography (OCT) after uncomplicated glaucoma filtration surgery. This prospective study included 32 patients (34 eyes) with open-angle glaucoma, which underwent trabeculectomy with or without use of mitomycin C. Exclusion criteria were macular edema, uveitis, age-related macular degeneration, blurred optical media, secondary glaucoma and angle-closure glaucoma. All standard clinical examinations were made before surgery, at the 2nd day, 1 week and 1 month after surgery. Tomography of the macula was performed during every examination using Cirrus HD OCT for the analysis of central subfield thickness. Results show that thickening of the macula was slightly higher 1 week and 1 month after operation in comparison with baseline end 2nd day postoperativelly. There was no significant difference in the change of macular thickness in patients who have used topical prostaglandins compared with those who have used other topical medications. Also, there was no difference in macular changes between patients treated with or without mitomycin C. In conclusion, we found a slight subclinical increase in macular thickness after uncomplicated trabeculectomy, for which we considered that was the result in reduction of intraocular pressure after glaucoma surgery. Macular thickening after glaucoma filtering surgery could be a physiological reaction to the stress of the retina caused by a sudden reduction of intraocular pressure and it is the consequence of altered relationship between capillary pressure and interstitial fluid pressure.
C1 [Sesar, Antonio; Cavar, Ivan; Sesar, Anita Pusic; Sesar, Irena] Clin Hosp Mostar, Dept Ophthalmol, Mostar 88000, Bosnia & Herceg.
   [Geber, Mia Zoric; Laus, Katia Novak; Vatavuk, Zoran; Mandic, Zdravko] Univ Zagreb, Univ Hosp Ctr Sestre Milosrdnice, Dept Ophthalmol, Zagreb 41000, Croatia.
C3 University of Mostar; University of Zagreb; University of Zagreb, School
   of Dental Medicine
RP Sesar, A (通讯作者)，Clin Hosp Mostar, Dept Ophthalmol, Bijeli Brijeg Bb, Mostar 88000, Bosnia & Herceg.
EM antoniosesar@yahoo.com
RI Cavar, Ivan/HCI-4973-2022
OI Cavar, Ivan/0000-0002-0685-3982
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NR 35
TC 10
Z9 12
U1 0
U2 4
PU COLLEGIUM ANTROPOLOGICUM
PI ZAGREB
PA INST ANTHROPOLOGICAL RESEARCH, GAJEVA 32, PO BOX 290, HR-10000 ZAGREB,
   CROATIA
SN 0350-6134
J9 COLLEGIUM ANTROPOL
JI Coll. Anthropol.
PD SEP
PY 2013
VL 37
IS 3
BP 841
EP 845
PG 5
WC Anthropology
WE Social Science Citation Index (SSCI)
SC Anthropology
GA 245SK
UT WOS:000326483900025
PM 24308226
DA 2022-11-30
ER

PT J
AU Bhargava, M
   Ikram, MK
   Wong, TY
AF Bhargava, M.
   Ikram, M. K.
   Wong, T. Y.
TI How does hypertension affect your eyes?
SO JOURNAL OF HUMAN HYPERTENSION
LA English
DT Review
DE blood pressure; retinopathy; cardiovascular disease; retinal vascular
   conditions
ID RETINAL-VEIN-OCCLUSION; ISCHEMIC OPTIC NEUROPATHIES; CARDIOVASCULAR
   RISK-FACTORS; MACULAR EDEMA SECONDARY; BLOOD-PRESSURE CONTROL; TARGET
   ORGAN DAMAGE; BLUE MOUNTAINS EYE; ATHEROSCLEROSIS RISK; MICROVASCULAR
   ABNORMALITIES; DIABETIC-RETINOPATHY
AB Hypertension has profound effects on various parts of the eye. Classically, elevated blood pressure results in a series of retinal microvascular changes called hypertensive retinopathy, comprising of generalized and focal retinal arteriolar narrowing, arteriovenous nicking, retinal hemorrhages, microaneurysms and, in severe cases, optic disc and macular edema. Studies have shown that mild hypertensive retinopathy signs are common and seen in nearly 10% of the general adult non-diabetic population. Hypertensive retinopathy signs are associated with other indicators of end-organ damage (for example, left ventricular hypertrophy, renal impairment) and may be a risk marker of future clinical events, such as stroke, congestive heart failure and cardiovascular mortality. Furthermore, hypertension is one of the major risk factors for development and progression of diabetic retinopathy, and control of blood pressure has been shown in large clinical trials to prevent visual loss from diabetic retinopathy. In addition, several retinal diseases such as retinal vascular occlusion (artery and vein occlusion), retinal arteriolar emboli, macroaneurysm, ischemic optic neuropathy and age-related macular degeneration may also be related to hypertension; however, there is as yet no evidence that treatment of hypertension prevents vision loss from these conditions. In management of patients with hypertension, physicians should be aware of the full spectrum of the relationship of blood pressure and the eye. Journal of Human Hypertension (2012) 26, 71-83; doi:10.1038/jhh.2011.37; published online 21 April 2011
C1 [Wong, T. Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore 168751, Singapore.
   [Ikram, M. K.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
   [Wong, T. Y.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia.
C3 National University of Singapore; Singapore National Eye Center; Erasmus
   University Rotterdam; Erasmus MC; Centre for Eye Research Australia;
   University of Melbourne
RP Wong, TY (通讯作者)，Natl Univ Singapore, Singapore Eye Res Inst, Singapore Natl Eye Ctr, 11 3rd Hosp Ave, Singapore 168751, Singapore.
EM ophwty@nus.edu.sg
RI Wong, Tien Yin/AAC-9724-2020
OI Wong, Tien Yin/0000-0002-8448-1264; Ikram, Mohammad
   Kamran/0000-0003-0173-9571
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NR 104
TC 78
Z9 80
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9240
EI 1476-5527
J9 J HUM HYPERTENS
JI J. Hum. Hypertens.
PD FEB
PY 2012
VL 26
IS 2
BP 71
EP 83
DI 10.1038/jhh.2011.37
PG 13
WC Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA 879DK
UT WOS:000299309700001
PM 21509040
DA 2022-11-30
ER

PT J
AU Chen, J
   Lee, L
AF Chen, Jennifer
   Lee, Lawrence
TI Clinical applications and new developments of optical coherence
   tomography: an evidence-based review
SO CLINICAL AND EXPERIMENTAL OPTOMETRY
LA English
DT Review
DE diagnostic imaging; macula; optical coherence tomography; optic nerve;
   retina
ID NERVE-FIBER LAYER; DIABETIC MACULAR EDEMA; SCANNING LASER POLARIMETRY;
   INTRAVITREAL BEVACIZUMAB AVASTIN; VITREOMACULAR TRACTION SYNDROME;
   FUNDUS FLUORESCEIN ANGIOGRAPHY; MONITOR PHOTODYNAMIC THERAPY; RETINAL
   THICKNESS ANALYSIS; IN-SITU KERATOMILEUSIS; ULTRAHIGH-RESOLUTION
AB Optical coherence tomography (OCT) is a new imaging modality that has increasingly become an indispensable tool in clinical practice for the diagnosis and management of ocular diseases involving the macula, optic nerve and anterior segment. The instrument is an advanced imaging technique that provides unprecedented high resolution and cross-sectional tomographic images of the ocular microstructure in situ, and in real time. Since its introduction about four years ago, a multitude of advantages has made OCT an essential instrument in ophthalmic imaging. The technique has fast image acquisition speed and non-contact, non-invasive applicability, allowing a non-excisional 'optical biopsy' to be performed. The purpose of this paper is to provide an evidence-based review of the increasing role of OCT in the diagnosis and management of ocular disorders, particularly in age-related macular degeneration, diabetic macular oedema, macular hole, epiretinal membrane and glaucoma. Being one of the first users of OCT in Australia, our clinical experiences will be highlighted and clinical examples of various conditions will be presented to provide an overview of the immense implications of OCT in practice. The latest developments of the OCT revolution, in relation to combining OCT with fundus photography and scanning laser ophthalmoscopy, will also be described. New developments of three-dimensional visualisation of tissue morphology with future models of ultra-high speed, ultra-high resolution OCT may further enhance the early diagnosis, monitoring of disease progression and assessment of treatment efficacy, facilitated by this powerful technology.
C1 City Eye Ctr, Brisbane, Qld, Australia.
   Univ Queensland, Royal Brisbane Hosp, Dept Ophthalmol, Brisbane, Qld, Australia.
   Queensland Univ Technol, Inst Hlth Biomed Innovat, Sch Optometry, Brisbane, Qld, Australia.
C3 Royal Brisbane & Women's Hospital; University of Queensland; Queensland
   University of Technology (QUT)
RP Chen, J (通讯作者)，City Eye Ctr, Brisbane, Qld, Australia.
EM eye@cityeye.com.au
RI Lee, Lawrence/D-9590-2011
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NR 139
TC 61
Z9 63
U1 1
U2 12
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 SEP
PY 2007
VL 90
IS 5
BP 317
EP 335
DI 10.1111/j.1444-0938.2007.00151.x
PG 19
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 203IE
UT WOS:000248967500002
PM 17697178
OA Bronze
DA 2022-11-30
ER

PT J
AU Peate, WF
AF Peate, W. F.
TI Work-related eye injuries and illnesses
SO AMERICAN FAMILY PHYSICIAN
LA English
DT Article
ID CORNEAL; RHINOCONJUNCTIVITIS; ALLERGY; UPDATE; ASTHMA
AB More than 65,000 work-related eye injuries and illnesses, causing significant morbidity and disability, are reported in the United States annually. A well-equipped eye tray includes fluorescein dye, materials for irrigation and foreign body removal, a short-acting mydriatic agent, and topical anesthetics and antibiotics. The tray should be prepared in advance in case of an eye injury. Eye patching does not improve cornea reepithelialization or discomfort from corneal abrasions. Blunt trauma to the eye from a heavy object can cause a blow-out fracture. Sudden eye pain after working with a chisel, hammer, grinding wheel, or saw suggests a penetrating globe injury. Chemical eye burns require immediate copious irrigation. Nontraumatic causes of ocular illness are underreported; work-related allergic conjunctivitis increasingly has been recognized among food handlers and agriculture workers who are exposed to common spices, fruits, and vegetables. The patient's history of eye injury guides the diagnosis. Primary prevention and patient counseling on proper eye protection is essential because over 90 percent of injuries can be avoided with the use of eye protection. As laser use increases in industry and medical settings, adequate personal protection is needed to prevent cataracts. Outdoor workers exposed to significant ultraviolet rays need sun protection and safety counseling to prevent age-related macular degeneration. Contact lenses do not provide eye protection, and physicians should be familiar with guidelines for the use of contacts in the workplace.
C1 Univ Arizona, Coll Publ Hlth, Tucson, AZ 85724 USA.
   Univ Arizona, Coll Med, Tucson, AZ USA.
C3 University of Arizona; University of Arizona
RP Peate, WF (通讯作者)，Univ Arizona, Coll Publ Hlth, 1295 N Martin Ave,POB 245210, Tucson, AZ 85724 USA.
EM peate@email.arizona.edu
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NR 29
TC 35
Z9 42
U1 0
U2 7
PU AMER ACAD FAMILY PHYSICIANS
PI KANSAS CITY
PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA
SN 0002-838X
EI 1532-0650
J9 AM FAM PHYSICIAN
JI Am. Fam. Physician
PD APR 1
PY 2007
VL 75
IS 7
BP 1017
EP 1022
PG 6
WC Primary Health Care; Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 154WO
UT WOS:000245538800010
PM 17427615
DA 2022-11-30
ER

PT J
AU Jurklies, B
   Bornfeld, N
   Schilling, H
AF Jurklies, Bernhard
   Bornfeld, Norbert
   Schilling, Harald
TI Photodynamic therapy using verteporfin for choroidal neovascularization
   associated with angioid streaks - Long-term effects
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE photodynamic therapy, long-term effects; angioid streaks; choroidal
   neovascularization
ID MEMBRANES; MYOPIA
AB Aim: To investigate the safety and efficacy of photodynamic therapy with verteporfin (PDT) in patients with choroidal neovascularization associated with angioid streaks (CNVAS). Methods: A nonrandomized, prospective clinical investigation of 12 patients with CNVAS was performed. PDT was based on the criteria concerning the treatment of age-related macular degeneration. Results: The mean follow-up was 41.75 months (range 24-60). The mean number of (re)treatments was 3.3 (range 2-7). Visual acuity improved by at least 1 line in 42%, was stable within 2 lines in 33%, decreased by at least 1 line in 58% and by > 3 lines in 25% of the patients. The mean visual acuity was 0.30 (range 0.2-0.5) prior to and 0.17 (range 0.03-0.6) after the final PDT. The mean visual acuity of the contralateral eye was 0.1. 75% of contralateral eyes and 25% of the treated eyes had a final visual acuity of <= 0.1 (20/200). At the final follow-up, a significant enlargement of the lesion size was noted in 92% of the cases. Conclusion: Using the current (re)treatment criteria, PDT does not appear to limit the growth of CNVAS. Com- pared to the aggressive natural course and to the limited treatment options, PDT may at least in part help to stabilize macular function over a limited period of time. Copyright (c) 2006 S. Karger AG, Basel.
C1 Univ Klinikum Essen, Zentrum Augenheilkunde, Dept Ophthalmol, DE-45122 Essen, Germany.
C3 University of Duisburg Essen
RP Jurklies, B (通讯作者)，Univ Klinikum Essen, Zentrum Augenheilkunde, Dept Ophthalmol, Hufelandstr 55, DE-45122 Essen, Germany.
EM bernhard.jurklies@uni-essen.de
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NR 22
TC 21
Z9 25
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2006
VL 38
IS 4
BP 209
EP 217
DI 10.1159/000093071
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 073SA
UT WOS:000239761700007
PM 16679809
DA 2022-11-30
ER

PT J
AU Yatsenko, AN
   Wiszniewski, W
   Zaremba, CM
   Jamrich, M
   Lupski, JR
AF Yatsenko, AN
   Wiszniewski, W
   Zaremba, CM
   Jamrich, M
   Lupski, JR
TI Evolution of ABCA4 proteins in vertebrates
SO JOURNAL OF MOLECULAR EVOLUTION
LA English
DT Article
DE ABCA4; photoreceptor; phylogenetic tree; conserved regions; selection
ID DISEASE GENE ABCR; STARGARDT MACULAR DYSTROPHY; CONE-ROD DYSTROPHY; RIM
   PROTEIN; TRANSPORTER SUPERFAMILY; RETINITIS-PIGMENTOSA; BIOCHEMICAL
   DEFECTS; FUNCTIONAL-ANALYSIS; VISUAL PIGMENTS; MUTATIONS
AB The ABCA4 (ABCR) gene encodes a retinal-specific ATP-binding cassette transporter. Mutations in ABCA4 are responsible for several recessive macular dystrophies and susceptibility to age related macular degeneration (AMD). The protein appears to function as a flippase of all-trans-retinal-dehyde and/or its derivatives across the membrane of outer segment disks and is a potentially important element in recycling visual cycle metabolites. However, the understanding of ABCA4's role in the visual cycle is limited due to the lack of a direct functional assay. An evolutionary analysis of ABCA4 may aid in the identification of conserved elements, the preservation of which implies functional importance. To date, only human, murine, and bovine ABCA4 genes are described. We have identified ABCA4 genes from African (Xenopus laevis) and Western (Silurana tropicalis) clawed frogs. A comparative analysis describing the evolutionary relationships between the frog ABCA4s, annotated T. rubripes ABCA4, and mammalian ABCA4 proteins was carried out. Several segments are conserved in both intradiscal loop (IL) domains, in addition to the transmembrane and ATP-binding domains. Nonconserved segments were found in the IL and cytoplasmic linker domains. Maximum likelihood analyses of the aligned sequences strongly suggest that ABCA4 was Subject to purifying selection. Collectively, these data corroborate the current evolutionary model where two distinct ABCA half-transporter progenitors were combined to form a full ABCA4 progenitor in ancestral chordates. We speculate that evolutionary alterations may increase the retinoid metabolite recycling capacity of ABCA4 and may improve dark adaptation.
C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   Baylor Coll Med, Program Cell & Mol Biol, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College
   of Medicine
RP Lupski, JR (通讯作者)，Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
EM jlupski@bcm.tmc.edu
OI Yatsenko, Alexander/0000-0002-1690-0172
FU NEI NIH HHS [EY12505, EY13255, EY12163] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [R01EY013255, R01EY012505, R01EY012163] Funding
   Source: NIH RePORTER
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NR 45
TC 9
Z9 10
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0022-2844
EI 1432-1432
J9 J MOL EVOL
JI J. Mol. Evol.
PD JAN
PY 2005
VL 60
IS 1
BP 72
EP 80
DI 10.1007/s00239-004-0118-4
PG 9
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
   Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
   Heredity
GA 885DI
UT WOS:000226136900006
PM 15696369
DA 2022-11-30
ER

PT J
AU Hanschmann, EM
   Wilms, C
   Falk, L
   Holubiec, MI
   Mennel, S
   Lillig, CH
   Godoy, JR
AF Hanschmann, Eva -Maria
   Wilms, Christina
   Falk, Lisa
   Holubiec, Mariana Ines
   Mennel, Stefan
   Lillig, Christopher Horst
   Godoy, Jose Rodrigo
TI Cytosolic glutaredoxin 1 is upregulated in AMD and controls retinal
   pigment epithelial cells proliferation via ?-catenin
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Age -related macular degeneration; Glutaredoxin; ARPE-19; Hypoxia;
   fi-catenin
ID MOLECULAR-MECHANISMS; OXIDATIVE STRESS; BETA-CATENIN; THIOREDOXIN;
   DAMAGE; APOPTOSIS; MIGRATION; HEALTH
AB Thioredoxin (Trx) family proteins are key players in redox signaling. Here, we have analyzed glutaredoxin (Grx) 1 and Grx2 in age-related macular degeneration (AMD) and in retinal pigment epithelial (ARPE-19) cells. We hypothesized that these redoxins regulate cellular functions and signaling circuits such as cell proliferation, Wnt signaling and VEGF release that have been correlated to the pathophysiology of AMD. ARPE-19 cells were transfected with specific siRNAs to silence the expression of Grx1 and Grx2 and were analyzed for proliferation/viability, migration capacity, fi-catenin activation, and VEGF release. An active site-mutated C-X-X-S Grx1 was utilized to trap interacting proteins present in ARPE-19 cell extracts. In both, AMD retinas and in ARPE-19 cells incubated under hypoxia/reoxygenation conditions, Grx1 showed an increased nuclear localization. Grx1-silenced ARPE-19 cells showed a significantly reduced prolifer-ation and migration rate. Our trapping approach showed that Grx1 interacts with fi-catenin in a dithiol-disulfide exchange reaction. Knock-down of Grx1 led to a reduction in both total and active fi-catenin levels. These findings add redox control to the regulatory mechanisms of fi-catenin signaling in the retinal pigment epithelium and open the door to novel therapeutic approaches in AMD that is currently treated with VEGF-inhibitors.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
C1 [Hanschmann, Eva -Maria; Wilms, Christina] Heinrich Heine Univ, Med Fac, Dept Neurol, Dusseldorf, Germany.
   [Hanschmann, Eva -Maria; Falk, Lisa; Lillig, Christopher Horst] Univ Greifswald, Univ Med, Inst Med Biochem & Mol Biol, Greifswald, Germany.
   [Holubiec, Mariana Ines] Univ Buenos Aires, Fac Med, Inst Biol Celular & Neurociencia, Buenos Aires, Argentina.
   [Mennel, Stefan] Hosp Feldkirch, Feldkirch, Austria.
   [Godoy, Jose Rodrigo] Long Isl Univ, Coll Vet Med, Dept Vet Biomed Sci, Brookville, NY 11201 USA.
   [Godoy, Jose Rodrigo] Long Isl Univ, Coll Vet Med, Dept Vet Biomed Sci, 720 Northern Blvd, Brookville, NY 11548 USA.
C3 Heinrich Heine University Dusseldorf; Ernst Moritz Arndt Universitat
   Greifswald; University of Buenos Aires
RP Godoy, JR (通讯作者)，Long Isl Univ, Coll Vet Med, Dept Vet Biomed Sci, 720 Northern Blvd, Brookville, NY 11548 USA.
EM Jose.Godoy@liu.edu
FU Deutsche Forschungsgemeinschaft [Ha 8334/2-2, Li984/3-1, Li984/3-2,
   Li984/4-1, SPP1710]; Research Office of Long Island University's College
   of Veterinary Medicine
FX The authors gratefully acknowledge the financial support by the Deutsche
   Forschungsgemeinschaft (SPP1710-Dynamics of thiol-based redox switches
   in cellular physiology, Ha 8334/2-2, Li984/3-1, Li984/3-2, Li984/4-1)
   and the Research Office of Long Island University's College of
   Veterinary Medicine.
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NR 30
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD AUG 27
PY 2022
VL 618
BP 24
EP 29
DI 10.1016/j.bbrc.2022.06.030
PG 6
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 3B1BW
UT WOS:000827684400004
PM 35714567
OA hybrid
DA 2022-11-30
ER

PT J
AU Hassan, JW
   Bhatwadekar, AD
AF Hassan, Jannah Waled
   Bhatwadekar, Ashay D.
TI Senolytics in the treatment of diabetic retinopathy
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Review
DE diabetic retinopathy; senolytics; diabetes; inflammation;
   pharmacological agents
ID CELLULAR SENESCENCE; BCL-XL; CELLS; DAMAGE
AB Diabetic retinopathy (DR) is the most common complication of diabetes. DR is characterized by damage to retinal vasculature resulting in vision impairment and, if untreated, could eventually lead to blindness. The pathogenic mechanism of DR is complex; emerging studies suggest that premature senescence of retinal cells and subsequent secretion of inflammatory cytokines exacerbate DR disease state by stimulating paracrine senescence, pathological angiogenesis, and reparative vascular regeneration. Senolytics are a new class of drugs that can selectively clear out senescent cells from the retina, thus holding a significant promise in DR treatment and prevention. In this review, we discuss the critical role of cellular senescence in DR's pathogenesis; A literature review was conducted in September of 2021 to explore the therapeutic potential of senolytics in the treatment of DR. Studies that were relevant to the research topic were selected through multiple keyword searches in the search engine, PubMed and thoroughly reviewed using abstracts and full-text articles. We present evidence from animal models for studying cellular senescence in DR and discuss multiple pathogenic mechanisms in cellular senescence and its involvement in DR. We also discuss the current state of pharmaceutical development at preclinical and clinical stages focusing on the senolytic drugs navitoclax, 17-DMAG, piperlongumine, UBX-1325, dasatinib quercetin, and fisetin. In particular, UBX-1325 holds a promising prospect for DR treatment based on the positive outcome of early clinical studies in individuals with diabetic macular edema (DME) and wet age-related macular degeneration.
C1 [Hassan, Jannah Waled; Bhatwadekar, Ashay D.] Indiana Univ, Dept Ophthalmol, Indianapolis, IN 47405 USA.
C3 Indiana University System; Indiana University-Purdue University
   Indianapolis
RP Bhatwadekar, AD (通讯作者)，Indiana Univ, Dept Ophthalmol, Indianapolis, IN 47405 USA.
EM abhatwad@iupui.edu
FU National Institute of Health (NIH)'s-National Eye Institute (NEI)
   [R01EY027779, R01EY032080]; Research to Prevent Blindness; Life in
   Health Science Internship (LHSI) program of Indiana University; Purdue
   University at Indianapolis (IUPUI)
FX The research in AB's lab is supported by funding from the National
   Institute of Health (NIH)'s-National Eye Institute (NEI) grants,
   R01EY027779 and R01EY032080 and a challenge grant from Research to
   Prevent Blindness to the Department of Ophthalmology. JH's internship is
   supported by funding from Life in Health Science Internship (LHSI)
   program of Indiana University and Purdue University at Indianapolis
   (IUPUI).
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NR 51
TC 1
Z9 1
U1 1
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD AUG 26
PY 2022
VL 13
AR 896907
DI 10.3389/fphar.2022.896907
PG 9
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 6D9IZ
UT WOS:000882998900001
PM 36091769
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Yamaguchi, Y
   Zampino, M
   Tanaka, T
   Bandinelli, S
   Moaddel, R
   Fantoni, G
   Candia, J
   Ferrucci, L
   Semba, RD
AF Yamaguchi, Yuko
   Zampino, Marta
   Tanaka, Toshiko
   Bandinelli, Stefania
   Moaddel, Ruin
   Fantoni, Giovanna
   Candia, Julian
   Ferrucci, Luigi
   Semba, Richard D.
TI The Plasma Proteome Fingerprint Associated with Circulating Carotenoids
   and Retinol in Older Adults
SO JOURNAL OF NUTRITION
LA English
DT Article
DE carotene; carotenoid; cryptoxanthin; lutein; lycopene; protein;
   proteomics; zeaxanthin; retinol
ID CARDIOVASCULAR-DISEASE; BLOOD-CONCENTRATIONS; DIETARY-INTAKE; ALL-CAUSE;
   RISK; SERUM; MORTALITY; CANCER; THROMBOSPONDIN-2; METAANALYSIS
AB Background: Although diets rich in carotenoids are associated with reduced risks of cardiovascular disease, age-related macular degeneration, disability, and other adverse aging outcomes, the underlying biological mechanisms are not fully elucidated.
   Objectives: To characterize the plasma proteome fingerprint associated with circulating carotenoid and retinol concentrations in older adults.
   Methods: In 728 adults >= 65 y participating in the lnvecchiare in Chianti (InCHIANTI) Study, plasma a-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene were measured using HPLC. The SOMAscan assay was used to measure 1301 plasma proteins. Multivariable linear regression models were used to examine the relationship of individual carotenoids and retinol with plasma proteins. A false discovery rate approach was used to deal with multiple comparisons using a q-value < 0.05.
   Results: Plasma beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene were associated with 85, 39, 4, 2, and 5 plasma proteins, respectively, in multivariable linear regression models adjusting for potential confounders (q < 0.05). No proteins were associated with alpha-carotene or retinol. Two or more carotenoids were positively associated with ferritin, 6-phosphogluconate dehydrogenase (decarboxylating), hepcidin, thrombospondin-2, and choline/ethanolamine kinase. The proteins associated with circulating carotenoids were related to energy metabolism, sirtuin signaling, inflammation and oxidative stress, iron metabolism, proteostasis, innate immunity, and longevity.
   Conclusions: The plasma proteomic fingerprint associated with elevated circulating carotenoids in older adults provides insight into the mechanisms underlying the protective role of carotenoids on health.
C1 [Yamaguchi, Yuko; Semba, Richard D.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
   [Yamaguchi, Yuko] Kobe Univ, Grad Sch Hlth Sci, Kobe, Hyogo, Japan.
   [Zampino, Marta; Tanaka, Toshiko; Moaddel, Ruin; Fantoni, Giovanna; Candia, Julian; Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA.
   [Bandinelli, Stefania] Azienda USL TOSCANA Ctr, Geriatr Unit, Florence, Italy.
   [Semba, Richard D.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Livable Future, Baltimore, MD USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Kobe University;
   National Institutes of Health (NIH) - USA; NIH National Institute on
   Aging (NIA); Johns Hopkins University; Johns Hopkins Bloomberg School of
   Public Health
RP Yamaguchi, Y (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.; Yamaguchi, Y (通讯作者)，Kobe Univ, Grad Sch Hlth Sci, Kobe, Hyogo, Japan.
EM y.yuko@port.kobe-u.ac.jp
RI bandinelli, stefania/AAL-4570-2020
OI Bandinelli, Stefania/0000-0002-6491-0850; Ferrucci,
   Luigi/0000-0002-6273-1613
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NR 59
TC 1
Z9 1
U1 0
U2 3
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 JAN
PY 2022
VL 152
IS 1
BP 40
EP 48
DI 10.1093/jn/nxab340
EA SEP 2021
PG 9
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA YK2GK
UT WOS:000745037900006
PM 34550359
OA Green Published
DA 2022-11-30
ER

PT J
AU Ahmed, I
   Johnston, RJ
   Singh, MS
AF Ahmed, Ishrat
   Johnston, Robert J., Jr.
   Singh, Mandeep S.
TI Pluripotent stem cell therapy for retinal diseases
SO ANNALS OF TRANSLATIONAL MEDICINE
LA English
DT Review
DE Retinitis pigmentosa (RP); age-related macular degeneration (AMD);
   embryonic stem cell (ESC); induced pluripotent stem cell (iPSC); retinal
   organoid
ID PIGMENT EPITHELIUM; MACULAR DEGENERATION; STARGARDT DISEASE;
   GENE-THERAPY; AUTOLOGOUS TRANSLOCATION; CHOROID TRANSLOCATION; EFFICIENT
   GENERATION; CLINICAL-TRIALS; VISUAL FUNCTION; TRANSPLANTATION
AB Pluripotent stem cells (PSCs), which include human embryonic stem cells (hESCs) and induced pluripotent stem cell (iPSC), have been used to study development of disease processes, and as potential therapies in multiple organ systems. In recent years, there has been increasing interest in the use of PSC-based transplantation to treat disorders of the retina in which retinal cells have been functionally damaged or lost through degeneration. The retina, which consists of neuronal tissue, provides an excellent system to test the therapeutic utility of PSC-based transplantation due to its accessibility and the availability of high -resolution imaging technology to evaluate effects. Preclinical trials in animal models of retinal diseases have shown improvement in visual outcomes following subretinal transplantation of PSC-derived photoreceptors or retinal pigment epithelium (RPE) cells. This review focuses on preclinical studies and clinical trials exploring the use of PSCs for retinal diseases. To date, several phase I/II clinical trials in patients with age-related macular degeneration (AMD) and Stargardt disease (STGD1) have demonstrated the safety and feasibility of PSC-derived RPE transplantation. Additional phase I/II clinical trials using PSC-derived RPE or photoreceptor cells for the treatment of AMD, STGD1, and also retinitis pigmentosa (RP) are currently in the pipeline. As this field continues to evolve, additional technologies may enhance PSC-derived cell transplantation through gene-editing of autologous cells, transplantation of more complex cellular structures such as organoids, and monitoring of transplanted cells through novel imaging technologies.
C1 [Ahmed, Ishrat; Singh, Mandeep S.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
   [Johnston, Robert J., Jr.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins
   University
RP Singh, MS (通讯作者)，Johns Hopkins Univ Hosp, Wilmer Eye Inst, 600 N Wolfe St, Baltimore, MD 21287 USA.
EM mandeep@jhmi.edu
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NR 118
TC 4
Z9 4
U1 1
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 AUG
PY 2021
VL 9
IS 15
AR 1279
DI 10.21037/atm-20-4747
PG 17
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA UA6LY
UT WOS:000685272900024
PM 34532416
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Roberts, SB
   Silver, RE
   Das, SK
   Fielding, RA
   Gilhooly, CH
   Jacques, PF
   Kelly, JM
   Mason, JB
   McKeown, NM
   Reardon, MA
   Rowan, S
   Saltzman, E
   Shukitt-Hale, B
   Smith, CE
   Taylor, AA
   Wu, DY
   Zhang, FF
   Panetta, K
   Booth, S
AF Roberts, Susan B.
   Silver, Rachel E.
   Das, Sai Krupa
   Fielding, Roger A.
   Gilhooly, Cheryl H.
   Jacques, Paul F.
   Kelly, Jennifer M.
   Mason, Joel B.
   McKeown, Nicola M.
   Reardon, Meaghan A.
   Rowan, Sheldon
   Saltzman, Edward
   Shukitt-Hale, Barbara
   Smith, Caren E.
   Taylor, Allen A.
   Wu, Dayong
   Zhang, Fang Fang
   Panetta, Karen
   Booth, Sarah
TI Healthy Aging-Nutrition Matters: Start Early and Screen Often
SO ADVANCES IN NUTRITION
LA English
DT Review
DE aging; nutrition; noncommunicable diseases; sarcopenia; cognition;
   age-related macular degeneration; diabetic retinopathy; obstructive
   sleep apnea; urinary incontinence; constipation
ID LIFE-STYLE INTERVENTION; MEDITERRANEAN DIET; OLDER-ADULTS;
   PROTEIN-INTAKE; UNITED-STATES; CALORIC RESTRICTION; COGNITIVE FUNCTION;
   GLYCEMIC-INDEX; DOUBLE-BLIND; CANCER-RISK
AB The amount of time spent in poor health at the end of life is increasing. This narrative review summarizes consistent evidence indicating that healthy dietary patterns and maintenance of a healthy weight in the years leading to old age are associated with broad prevention of all the archetypal diseases and impairments associated with aging including: noncommunicable diseases, sarcopenia, cognitive decline and dementia, osteoporosis, age-related macular degeneration, diabetic retinopathy, hearing loss, obstructive sleep apnea, urinary incontinence, and constipation. In addition, randomized clinical trials show that disease-specific nutrition interventions can attenuate progression-and in some cases effectively treat-many established aging-associated conditions. However, middle-aged and older adults are vulnerable to unhealthy dietary patterns, and typically consume diets with inadequate servings of healthy food groups and essential nutrients, along with an abundance of energy-dense but nutrient-weak foods that contribute to obesity. However, based on menu examples, diets that are nutrient-dense, plant-based, and with a moderately low glycemic load are better equipped to meet the nutritional needs of many older adults than current recommendations in US Dietary Guidelines. These summary findings indicate that healthy nutrition is more important for healthy aging than generally recognized. Improved public health messaging about nutrition and aging, combined with routine screening and medical referrals for age-related conditions that can be treated with a nutrition prescription, should form core components of a national nutrition roadmap to reduce the epidemic of unhealthy aging.
C1 [Roberts, Susan B.; Silver, Rachel E.; Das, Sai Krupa; Fielding, Roger A.; Gilhooly, Cheryl H.; Jacques, Paul F.; Kelly, Jennifer M.; Mason, Joel B.; McKeown, Nicola M.; Reardon, Meaghan A.; Rowan, Sheldon; Shukitt-Hale, Barbara; Smith, Caren E.; Taylor, Allen A.; Wu, Dayong; Booth, Sarah] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   [Saltzman, Edward; Zhang, Fang Fang] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
   [Panetta, Karen] Tufts Univ, Sch Engn, Medford, MA 02155 USA.
C3 Tufts University; United States Department of Agriculture (USDA); Tufts
   University; Tufts University
RP Roberts, SB (通讯作者)，Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
EM susan.roberts@tufts.edu
OI Mason, Joel/0000-0003-0307-9378; Jacques, Paul/0000-0001-5567-3147
FU AARP Foundation; USDA, Agricultural Research Service [58-8050-7-005]
FX Supported by the AARP Foundation, and the USDA, Agricultural Research
   Service under Cooperative Agreement No. 58-8050-7-005. Any opinions,
   findings, conclusions, or recommendations expressed in this publication
   are those of the authors and do not necessarily reflect the views of the
   USDA.
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NR 174
TC 16
Z9 16
U1 8
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2161-8313
EI 2156-5376
J9 ADV NUTR
JI Adv. Nutr.
PD JUL
PY 2021
VL 12
IS 4
BP 1438
EP 1448
DI 10.1093/advances/nmab032
EA APR 2021
PG 11
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Nutrition & Dietetics
GA WW8OT
UT WOS:000718169400024
PM 33838032
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Arias, JER
   Economopoulou, M
   Lopez, DAJ
   Kurzbach, A
   Yeung, KHA
   Englmaier, V
   Merdausl, M
   Schaarschmidt, M
   Ader, M
   Morawietz, H
   Funk, RHW
   Jaszai, J
AF Rojo Arias, Jesus E.
   Economopoulou, Matina
   Juarez Lopez, David A.
   Kurzbach, Anica
   Au Yeung, Kwan H.
   Englmaier, Vanessa
   Merdausl, Marie
   Schaarschmidt, Martin
   Ader, Marius
   Morawietz, Henning
   Funk, Richard H. W.
   Jaszai, Jozsef
TI VEGF-Trap is a potent modulator of vasoregenerative responses and
   protects dopaminergic amacrine network integrity in degenerative
   ischemic neovascular retinopathy
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE aflibercept; dopaminergic amacrine cells; endothelial tip cells;
   neovascularization; oxygen-induced retinopathy; vegf-trap
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL BARRIER BREAKDOWN;
   DIABETIC-RETINOPATHY; ANTI-VEGF; OSCILLATORY POTENTIALS; VISUAL
   DYSFUNCTION; CELL; MODEL; OXYGEN; ANGIOGENESIS
AB Retinal hypoxia triggers abnormal vessel growth and microvascular hyper-permeability in ischemic retinopathies. Whereas vascular endothelial growth factor A (VEGF-A) inhibitors significantly hinder disease progression, their benefits to retinal neurons remain poorly understood. Similar to humans, oxygen-induced retinopathy (OIR) mice exhibit severe retinal microvascular malformations and profound neuronal dysfunction. OIR mice are thus a phenocopy of human retinopathy of prematurity, and a proxy for investigating advanced stages of proliferative diabetic retinopathy. Hence, the OIR model offers an excellent platform for assessing morpho-functional responses of the ischemic retina to anti-angiogenic therapies. Using this model, we investigated the retinal responses to VEGF-Trap (Aflibercept), an anti-angiogenic agent recognizing ligands of VEGF receptors 1 and 2 that possesses regulatory approval for the treatment of neovascular age-related macular degeneration, macular edema secondary to retinal vein occlusion and diabetic macular edema. Our results indicate that Aflibercept not only reduces the severity of retinal microvascular aberrations but also significantly improves neuroretinal function. Aflibercept administration significantly enhanced light-responsiveness, as revealed by electroretinographic examinations, and led to increased numbers of dopaminergic amacrine cells. Additionally, retinal transcriptional profiling revealed the concerted regulation of both angiogenic and neuronal targets, including transcripts encoding subunits of transmitter receptors relevant to amacrine cell function. Thus, Aflibercept represents a promising therapeutic alternative for the treatment of further progressive ischemic retinal neurovasculopathies beyond the set of disease conditions for which it has regulatory approval.
C1 [Rojo Arias, Jesus E.; Juarez Lopez, David A.; Au Yeung, Kwan H.; Englmaier, Vanessa; Merdausl, Marie; Schaarschmidt, Martin; Funk, Richard H. W.; Jaszai, Jozsef] Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Anat, Dresden, Saxony, Germany.
   [Economopoulou, Matina] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Ophthalmol, Dresden, Saxony, Germany.
   [Kurzbach, Anica] Tech Univ Dresden, Univ Klinikum Carl Gustav Carus, Med Klin 3, Dresden, Saxony, Germany.
   [Kurzbach, Anica] German Ctr Diabet Res DZD eV, Munich, Germany.
   [Rojo Arias, Jesus E.; Ader, Marius] DFG Ctr Regenerat Therapies Dresden, Cluster Excellence, Dresden, Saxony, Germany.
   [Morawietz, Henning] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Div Vasc Endothelium & Microcirculat, Dept Med 3, Dresden, Saxony, Germany.
C3 Technische Universitat Dresden; Carl Gustav Carus University Hospital;
   Technische Universitat Dresden; Carl Gustav Carus University Hospital;
   Technische Universitat Dresden; Carl Gustav Carus University Hospital;
   German Research Foundation (DFG); Technische Universitat Dresden;
   Technische Universitat Dresden; Carl Gustav Carus University Hospital
RP Jaszai, J (通讯作者)，Tech Univ Dresden, Fac Med, Dept Anat, Fiedlerstr 42, D-01307 Dresden, Saxony, Germany.
EM jozsef.jaszai@tu-dresden.de
RI Ader, Marius/E-7535-2010
OI Ader, Marius/0000-0001-9467-7677; Kwan Ho, Au Yeung/0000-0003-2953-7955;
   Kurzbach, Anica/0000-0003-1531-3088
FU Bayer Vital GmbH; Excellence Initiative of the German Federal State
   Government (Institutional Strategy "Support the Best") [3-2,
   F03661-553-41B-1250000]
FX This work was supported by Bayer Vital GmbH and the Excellence
   Initiative of the German Federal State Government (Institutional
   Strategy "Support the Best", grant 3-2, F03661-553-41B-1250000). This
   study is investigator-initiated and investigator-driven. The authors are
   grateful to Dr. Tiago Santos-Ferreira, Jan Dudeck, and Martina Pinkert
   for technical assistance. The authors have no conflict of interest to
   declare.
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NR 114
TC 9
Z9 9
U1 3
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD MAY
PY 2020
VL 153
IS 3
BP 390
EP 412
DI 10.1111/jnc.14875
EA OCT 2019
PG 23
WC Biochemistry & Molecular Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA LH6AD
UT WOS:000492394800001
PM 31550048
OA hybrid
DA 2022-11-30
ER

PT J
AU Ehlken, C
   Guichard, MM
   Schlunck, G
   Buhler, AD
   Martin, G
   Agostini, HT
AF Ehlken, Christoph
   Guichard, Maria-Magdalena
   Schlunck, Guenther
   Buehler, Anima D.
   Martin, Gottfried
   Agostini, Hansjurgen T.
TI Expression of Angiogenic and Inflammatory Factors in Choroidal
   Neovascularisation-Derived Retinal Pigment Epithelium
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium;
   Inflammation; Choroidal neovascularisation; angiogenesis
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; VEGF; CELLS; MODEL;
   NEUROPILIN-1; PATHOGENESIS; INHIBITION; MECHANISMS; CYTOKINES
AB Purpose: Anti-angiogenic treatment is well established in the management of exudative age-related macular degeneration (AMD), but not sufficient in all patients. The characterisation of factors driving this chronic disease could serve to identify additional treatment options. The purpose of this study was to assess gene expression patterns and distinct changes in cells derived from surgically extracted choroidal neovascularisation (CNV) membranes. Materials and Methods: The expression of > 11,000 genes was analysed by means of a microarray in cells cultured from 2 late-stage CNV membranes compared to primary human retinal pigment epithelium (RPE) and ARPE-19 cells. A pathway analysis was performed to identify gene expression patterns associated with exudative AMD. Results: The analysis revealed significant alterations in gene sets associated with inflammatory processes in CNV-derived cells, involving the upregulation of pro-inflammatory factors IL6, C3, and C5, and downregulation of anti-inflammatory complement factor B and complement factor I. Factors associated with angiogenesis, such as VEGFA or ANGPT2, were not significantly regulated in the 2 RPE-derived cell lines. Conclusion: In late-stage CNV membrane-derived RPE, gene expression was shifted towards a pro-inflammatory state. Angiogenesis-associated factors were regulated differently in the 2 CNV-derived RPE membranes. While inflammation seems to be continuously stimulated by RPE associated with late exudative AMD, this appears not to be the case with regard to angioregulatory mechanisms. (C) 2017 S. Karger AG, Basel
C1 [Ehlken, Christoph; Guichard, Maria-Magdalena] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Ophthalmol, Fac Med, Campus Kiel, Kiel, Germany.
   [Ehlken, Christoph] Univ Freiburg, Fac Med, Med Ctr, Eye Ctr, Freiburg, Germany.
   [Buehler, Anima D.] Hannover Med Sch, Univ Eye Hosp, Hannover, Germany.
   [Guichard, Maria-Magdalena; Schlunck, Guenther; Buehler, Anima D.; Martin, Gottfried; Agostini, Hansjurgen T.] Univ Hosp Basel, Dept Ophthalmol, Basel, Switzerland.
C3 University of Kiel; Schleswig Holstein University Hospital; University
   of Freiburg; Hannover Medical School; University of Basel
RP Ehlken, C (通讯作者)，Univ Hosp Schleswig Holstein, Dept Ophthalmol, Campus Kiel,Arnold Heller Str 3, DE-24105 Kiel, Germany.
EM christoph.ehlken@uksh.de
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NR 39
TC 7
Z9 7
U1 0
U2 2
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2019
VL 61
IS 3
BP 174
EP 182
DI 10.1159/000481260
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HS0EZ
UT WOS:000463534900007
PM 29050001
DA 2022-11-30
ER

PT J
AU Maugeri, A
   Barchitta, M
   Mazzone, MG
   Giuliano, F
   Basile, G
   Agodi, A
AF Maugeri, Andrea
   Barchitta, Martina
   Mazzone, Maria Grazia
   Giuliano, Francesco
   Basile, Guido
   Agodi, Antonella
TI Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1
   Methylation Levels in ARPE-19 Cells under Oxidative Stress and
   Inflammation
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE retinal degeneration; DNA methylation; epigenetics; oxidative stress;
   inflammation
ID PIGMENT EPITHELIAL-CELLS; NF-KAPPA-B; AGE-RELATED MACULOPATHY; BEAVER
   DAM EYE; MACULAR DEGENERATION; 10-YEAR INCIDENCE; DNA METHYLATION;
   OCULAR DISEASES; GENE-EXPRESSION; IL17RC PROMOTER
AB The role of epigenetic alterations in the pathogenesis of retinal degenerative diseases, including age-related macular degeneration (AMD), has been pending so far. Our study investigated the effect of oxidative stress and inflammation on DNA methyltransferases (DNMTs) and Sirtuin 1 (SIRT1) functions, as well as on long interspersed nuclear element-1 (LINE-1) methylation, in human retinal pigment epithelial (ARPE-19) cells. Therefore, we evaluated whether treatment with resveratrol may modulate DNMT and SIRT1 functions and restore changes in LINE-1 methylation. Cells were treated with 25 mU/mL glucose oxidase (GOx) or 10 mu g/mL lipopolysaccharide (LPS) to mimic oxidative or inflammatory conditions, respectively. Oxidative stress decreased DNMT1, DNMT3a, DNMT3b, and SIRT1 expression (p-values < 0.05), as well as total DNMTs (28.5%; p < 0.0001) and SIRT1 (29.0%; p < 0.0001) activities. Similarly, inflammatory condition decreased DNMT1 and SIRT1 expression (p-values < 0.05), as well as total DNMTs (14.9%; p = 0.007) and SIRT1 (20.1%; p < 0.002) activities. Interestingly, GOx- and LPS-treated cells exhibited lower LINE-1 methylation compared to controls (p-values < 0.001). We also demonstrated that treatment with 10 mu M resveratrol for 24 h counteracted the detrimental effect on DNMT and SIRT1 functions, and LINE-1 methylation, in cells under oxidative and inflammatory conditions. However, further studies should explore the perspectives of resveratrol as a suitable strategy for the prevention and/or treatment of retinal degenerative diseases.
C1 [Maugeri, Andrea; Barchitta, Martina; Agodi, Antonella] Univ Catania, Dept Med & Surg Sci & Adv Technol GF Ingrassia, Via S Sofia 87, I-95123 Catania, Italy.
   [Mazzone, Maria Grazia; Giuliano, Francesco] SIFI SpA, Dept Res & Dev, Via Ercole Patti 36, I-95025 Catania, Italy.
   [Basile, Guido] Univ Catania, Dept Gen Surg & Med Surg Specialties, Via Plebiscito 628, I-95124 Catania, Italy.
C3 University of Catania; University of Catania
RP Agodi, A (通讯作者)，Univ Catania, Dept Med & Surg Sci & Adv Technol GF Ingrassia, Via S Sofia 87, I-95123 Catania, Italy.
EM andreamaugeri88@gmail.com; martina.barchitta@unict.it;
   mariagrazia.mazzone@sifigroup.com; francesco.giuliano@sifigroup.com;
   gbasile@unict.it; agodia@unict.it
RI Agodi, Antonella/B-3501-2011; Maugeri, Andrea/K-1018-2017; Barchitta,
   Martina/A-1362-2015; Agodi, Antonella/AIF-3938-2022
OI Agodi, Antonella/0000-0002-4405-8162; Maugeri,
   Andrea/0000-0003-2655-8574; Barchitta, Martina/0000-0002-0905-5003;
   Agodi, Antonella/0000-0002-4405-8162; BASILE, Guido/0000-0002-7171-7637
FU Department of Medical and Surgical Sciences and Advanced Technologies
   "GF Ingrassia", Universita di Catania (Piano Triennale di Sviluppo delle
   Attivita di Ricerca Scientifica del Dipartimento)
FX Andrea Maugeri, Martina Barchitta, and Antonella Agodi are supported by
   the Department of Medical and Surgical Sciences and Advanced
   Technologies "GF Ingrassia", Universita di Catania (Piano Triennale di
   Sviluppo delle Attivita di Ricerca Scientifica del Dipartimento
   2016-18).
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NR 59
TC 59
Z9 60
U1 3
U2 10
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 JUL
PY 2018
VL 19
IS 7
AR 2118
DI 10.3390/ijms19072118
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA GR6UX
UT WOS:000442807400297
PM 30037017
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Martins, A
   Farinha, C
   Raimundo, M
   Lopes, M
   Santos, AR
   Melo, P
   Marques, M
   Marques, JP
   Barreto, P
   Cachulo, ML
   Neves, C
   Cunha-Vaz, J
   Silva, R
AF Martins, Amelia
   Farinha, Claudia
   Raimundo, Miguel
   Lopes, Marta
   Santos, Ana Rita
   Melo, Pedro
   Marques, Marco
   Marques, Joao Pedro
   Barreto, Patricia
   Cachulo, Maria Luz
   Neves, Catarina
   Cunha-Vaz, Jose
   Silva, Rufino
TI Multimodal Evaluation of the Fellow Eye of Patients with Retinal
   Angiomatous Proliferation
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Fellow eye; Imaging markers; Optical coherence tomography angiography;
   Retinal angiomatous proliferation; Spectral-domain optical coherence
   tomography
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; TYPE-3
   NEOVASCULARIZATION; GEOGRAPHIC ATROPHY; FEATURES
AB Introduction: We conducted a multimodal, cross-sectional evaluation. Methods: Eyes were divided into 4 study groups: controls, early/intermediate age-related macular degeneration (AMD), fellow eyes of retinal angiomatous proliferation (RAP), and RAP eyes. Patients were evaluated with spectral-domain optical coherence tomography (OCT), enhanced depth imaging-OCT, and OCT angiography (OCTA). OCTA images were processed to generate maps of the vessel density and perfusion density of the superficial and deep retinal layers (SRL and DRL) and the choriocapillaris level (CL). The thickness of the outer nuclear layer and choroid was manually assessed. Results: We included 135 eyes of 100 patients ( 51 controls, 30 AMD, 42 RAP, and 12 fellow eyes). The fellow eyes showed a significantly lower vascular perfusion of the SRL, DRL, and CL (p < 0.02) than the early/intermediate AMD and control eyes did. Similarly, RAP eyes presented a lower vascular perfusion of the DRL and CL (p < 0.05). Besides, structural analyses of the fellow eyes and RAP eyes revealed a significantly higher prevalence of macular pigmentary changes, atrophy of the retinal pigment epithelium, hyper-reflective "clumps" above flat drusen, amongst others, than early/intermediate AMD and control eyes (p < 0.05). Conclusion: We present the first report on the OCTA analysis of the fellow eye of patients with RAP. The reduced perfusion density and vessel density observed contributes, in association with clearly defined structural changes, to a wider characterization of RAP as a distinctive phenotype. (C) 2017 S. Karger AG, Basel
C1 [Martins, Amelia; Farinha, Claudia; Raimundo, Miguel; Marques, Marco; Marques, Joao Pedro; Cachulo, Maria Luz; Silva, Rufino] Ctr Hosp & Univ Coimbra, Ophthalmol Dept, P-3049 Coimbra, Portugal.
   [Farinha, Claudia; Lopes, Marta; Santos, Ana Rita; Melo, Pedro; Marques, Joao Pedro; Barreto, Patricia; Cachulo, Maria Luz; Neves, Catarina; Cunha-Vaz, Jose; Silva, Rufino] Univ Coimbra, Assoc Innovat & Biomed Res Light & Image, Coimbra, Portugal.
   [Farinha, Claudia; Marques, Joao Pedro; Cachulo, Maria Luz; Cunha-Vaz, Jose; Silva, Rufino] Univ Coimbra, Fac Med, Inst Biomed Imaging & Life Sci FMUC IBILI, Coimbra, Portugal.
C3 Universidade de Coimbra; Centro Hospitalar e Universitario de Coimbra
   (CHUC); Universidade de Coimbra; Universidade de Coimbra
RP Martins, A (通讯作者)，Ctr Hosp & Univ Coimbra, Ophthalmol Dept, P-3049 Coimbra, Portugal.
EM martins.amelia9@gmail.com
RI santos, ana/GWV-5678-2022; Marques, João Pedro/J-3584-2012; Silva,
   Rufino M/J-2817-2012; Farinha, Claudia/R-1392-2017
OI Marques, João Pedro/0000-0002-1014-0483; Silva, Rufino
   M/0000-0001-8676-0833; Farinha, Claudia/0000-0003-4596-0913; Cachulo,
   Maria Luz/0000-0002-0900-4548; B M Santos, Ana Rita/0000-0003-3761-3292;
   Cunha-Vaz, Jose/0000-0002-0947-9850
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NR 30
TC 5
Z9 5
U1 0
U2 3
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 2
BP 88
EP 97
DI 10.1159/000481262
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FV9NN
UT WOS:000424915200005
PM 29065425
DA 2022-11-30
ER

PT J
AU Datta, S
   Cano, M
   Ebrahimi, K
   Wang, L
   Handa, JT
AF Datta, Sayantan
   Cano, Marisol
   Ebrahimi, Katayoon
   Wang, Lei
   Handa, James T.
TI The impact of oxidative stress and inflammation on RPE degeneration in
   non-neovascular AMD
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Complement; Inflammation;
   Mitochondrial dynamics; Nrf2; Oxidative stress; Retinal pigment
   epithelium
ID RETINAL-PIGMENT EPITHELIUM; COMPLEMENT FACTOR-H; REQUIRES MITOCHONDRIAL
   ROS; MEMBRANE ATTACK COMPLEX; HEPARIN-BINDING DOMAIN; C-REACTIVE
   PROTEIN; MACULAR-DEGENERATION; NLRP3 INFLAMMASOME; BRUCHS MEMBRANE;
   RETICULAR PSEUDODRUSEN
AB The retinal pigment epithelium (RPE) is a highly specialized, unique epithelial cell that interacts with photoreceptors on its apical side and with Bruch's membrane and the choriocapillaris on its basal side. Due to vital functions that keep photoreceptors healthy, the RPE is essential for maintaining vision. With aging and the accumulated effects of environmental stresses, the RPE can become dysfunctional and die. This degeneration plays a central role in age-related macular degeneration (AMD) pathobiology, the leading cause of blindness among the elderly in western societies. Oxidative stress and inflammation have both physiological and potentially pathological roles in RPE degeneration. Given the central role of the RPE, this review will focus on the impact of oxidative stress and inflammation on the RPE with AMD pathobiology. Physiological sources of oxidative stress as well as unique sources from photo-oxidative stress, the phagocytosis of photoreceptor outer segments, and modifiable factors such as cigarette smoking and high fat diet ingestion that can convert oxidative stress into a pathological role, and the negative impact of impairing the cytoprotective roles of mitochondrial dynamics and the Nrf2 signaling system on RPE health in AMD will be discussed. Likewise, the response by the innate immune system to an inciting trigger, and the potential role of local RPE production of inflammation, as well as a potential role for damage by inflammation with chronicity if the inciting trigger is not neutralized, will be debated. (C) 2017 Elsevier Ltd. All rights reserved.
C1 [Datta, Sayantan; Cano, Marisol; Ebrahimi, Katayoon; Wang, Lei; Handa, James T.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
   [Ebrahimi, Katayoon] Univ Missouri, Mason Eye Inst, Columbia, MO USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; University of Missouri
   System; University of Missouri Columbia
RP Handa, JT (通讯作者)，MD 400 N Broadway,Smith Bldg Room 3015, Baltimore, MD 21287 USA.
EM jthanda@jhmi.edu
RI Wang, Lei/C-1902-2015
OI Wang, Lei/0000-0002-7957-1003
FU National Institutes of Health [EY14005, EY019044]; RPB; Wilmer Core
   Grant [EY001765]; Merlau family and Aleda Wright; NATIONAL EYE INSTITUTE
   [P30EY001765, R01EY019904, R01EY014005, R01EY027691] Funding Source: NIH
   RePORTER
FX The authors acknowledge the funding support from the National Institutes
   of Health (EY14005 (JTH), EY019044 (JTH)), RPB Senior Scientist Award
   (JTH), Wilmer Core Grant EY001765, Unrestricted Grant from RPB, and by
   the Merlau family and Aleda Wright. Dr. Handa is the Robert Bond Welch
   Professor.
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NR 284
TC 330
Z9 343
U1 8
U2 84
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 2017
VL 60
BP 201
EP 218
DI 10.1016/j.preteyeres.2017.03.002
PG 18
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FJ3HN
UT WOS:000412621500009
PM 28336424
OA Green Accepted
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Bee, YS
   Tu, LL
   Sheu, SJ
   Lin, HC
   Tang, JH
   Wang, JH
   Prea, SM
   Dusting, GJ
   Wu, DC
   Zhong, JX
   Bui, BV
   Tai, MH
   Liu, GS
AF Bee, Youn-Shen
   Tu, Leilei
   Sheu, Shwu-Jiuan
   Lin, Hsiu-Chen
   Tang, Jia-Hua
   Wang, Jiang-Hui
   Prea, Selwyn M.
   Dusting, Gregory J.
   Wu, Deng-Chyang
   Zhong, Jingxiang
   Bui, Bang V.
   Tai, Ming-Hong
   Liu, Guei-Sheung
TI Gene Delivery of Calreticulin Anti-Angiogenic Domain Attenuates the
   Development of Choroidal Neovascularization in Rats
SO HUMAN GENE THERAPY
LA English
DT Review
DE choroidal neovascularization; gene delivery; CAD; adenovirus
ID INHIBITS ANGIOGENESIS; TOPICAL APPLICATION; MEDIATED DELIVERY;
   VASOSTATIN; ADENOVIRUS; EXPRESSION; THERAPY; BIODISTRIBUTION;
   SUPPRESSION; METASTASIS
AB Choroidal neovascularization (CNV) is a common pathological feature in neovascular age-related macular degeneration, which is the leading cause of vision loss among elderly populations in developed countries. This study evaluated the effect of a novel endogenous inhibitor of angiogenesis, calreticulin antiangiogenic domain (CAD), subconjunctivally delivered by an adenoviral vector (Ad-CAD) in a rat model of laser-induced CNV. CAD was expressed in Ad-CAD-infected cells and inhibited the angiogenic activity in human umbilical vein endothelial cells in vitro. CAD expression was also found in various ocular tissues after in vivo subconjunctival Ad-CAD injection. Via bioluminescence imaging it is shown that a single subconjunctival injection of Ad-luciferase induced the expression of the transgene in the injected eyes within 24 h, which lasted for at least 112 days. Forty-two days after subconjunctival injection of Ad-CAD, retinal structure and function were unaffected, as measured using optical coherence tomography and electroretinography, respectively. After laser injury, subconjunctival Ad-CAD gene delivery significantly inhibited CNV lesions as measured via choroid flat-mounts (51% reduction at 21 days; p < 0.001), as well as by fundus fluorescein angiography (19.3%, 28.2%, 31%, and 27.5% reductions at days 21, 28, 35, and 42, respectively; p< 0.05) in rats. The data suggest that subconjunctival Ad-CAD gene therapy could effectively inhibit laser-induced CNV and might be an attractive therapeutic approach for the management of choroidal neovascularization.
C1 [Bee, Youn-Shen; Sheu, Shwu-Jiuan; Lin, Hsiu-Chen] Kaohsiung Vet Gen Hosp, Dept Ophthalmol, Kaohsiung, Taiwan.
   [Tang, Jia-Hua] Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung, Taiwan.
   [Bee, Youn-Shen] Yuh Ing Jr Coll Hlth Care & Management, Kaohsiung, Taiwan.
   [Bee, Youn-Shen] Natl Def Med Ctr, Taipei, Taiwan.
   [Tu, Leilei; Wang, Jiang-Hui; Dusting, Gregory J.; Liu, Guei-Sheung] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Australia.
   [Tu, Leilei; Zhong, Jingxiang] Jinan Univ, Affiliated Hosp 1, Dept Ophthalmol, Guangzhou, Guangdong, Peoples R China.
   [Sheu, Shwu-Jiuan] Natl Yang Ming Univ, Sch Med, Taipei, Taiwan.
   [Wang, Jiang-Hui; Dusting, Gregory J.; Liu, Guei-Sheung] Univ Melbourne, Dept Surg, Ophthalmol, East Melbourne, Australia.
   [Prea, Selwyn M.; Bui, Bang V.] Univ Melbourne, Dept Optometry & Vis Sci, East Melbourne, Australia.
   [Wu, Deng-Chyang; Tai, Ming-Hong] Kaohsiung Med Univ, Ctr Stem Cell Res, Kaohsiung, Taiwan.
   [Wu, Deng-Chyang] Kaohsiung Med Univ, Dept Internal Med, Div Gastroenterol, Kaohsiung, Taiwan.
   [Tai, Ming-Hong] Natl Sun Yat Sen Univ, Inst Biomed Sci, 70 Lien Hai Rd, Kaohsiung 804, Taiwan.
   [Tai, Ming-Hong] Natl Sun Yat Sen Univ, Ctr Neurosci, Kaohsiung, Taiwan.
C3 Kaohsiung Veterans General Hospital; Kaohsiung Veterans General
   Hospital; National Defense Medical Center; Centre for Eye Research
   Australia; Royal Victorian Eye & Ear Hospital; Jinan University;
   National Yang Ming Chiao Tung University; University of Melbourne;
   University of Melbourne; Kaohsiung Medical University; Kaohsiung Medical
   University; National Sun Yat Sen University; National Sun Yat Sen
   University
RP Tai, MH (通讯作者)，Natl Sun Yat Sen Univ, Inst Biomed Sci, 70 Lien Hai Rd, Kaohsiung 804, Taiwan.
EM minghongtai@gmail.com
RI Bui, Bang/AAD-2679-2021; Liu, Guei-Sheung/Q-6472-2018; Wang,
   Jiang-Hui/AAW-4653-2020
OI Bui, Bang/0000-0001-7298-1352; Liu, Guei-Sheung/0000-0003-3379-724X;
   Wang, Jiang-Hui/0000-0002-1551-9660
FU Kaohsiung Veterans General Hospital [VGHKS 97-106, 98-062, 99-062,
   100-066]; Kaohsiung Medical University [KMU-TP104G00, KMU-TP104G03,
   KMU-TP104G04]; NSYSU-MKU [102-P035]; Ministry of Science and Technology
   of Taiwan [MOST 103-2325-B-110-002]; National Health and Medical
   Research Council of Australia (NHMRC) [1061912]; Ophthalmic Research
   Institute of Australia; Angior Family Foundation; NHMRC; Victorian
   Government
FX This work was supported by grants from Kaohsiung Veterans General
   Hospital (VGHKS 97-106, 98-062, 99-062, and 100-066), Kaohsiung Medical
   University (KMU-TP104G00, KMU-TP104G03 and KMU-TP104G04), NSYSU-MKU
   Joint Project (102-P035), the Ministry of Science and Technology of
   Taiwan (MOST 103-2325-B-110-002), and the National Health and Medical
   Research Council of Australia (NHMRC#1061912), the Ophthalmic Research
   Institute of Australia, and the Angior Family Foundation. G.J.D.
   receives a Principal Research Fellowship from NHMRC. The Centre for Eye
   Research Australia receives Operational Infrastructure Support from the
   Victorian Government.
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NR 49
TC 1
Z9 1
U1 1
U2 18
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 MAY
PY 2017
VL 28
IS 5
BP 403
EP 414
DI 10.1089/hum.2016.035
PG 12
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 EU6PI
UT WOS:000401155500007
PM 28363247
DA 2022-11-30
ER

PT J
AU Silva, RLE
   Kanan, Y
   Mirando, AC
   Kim, J
   Shmueli, RB
   Lorenc, VE
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   Green, JJ
   Popel, AS
   Campochiaro, PA
AF Lima e Silva, Raquel
   Kanan, Yogita
   Mirando, Adam C.
   Kim, Jayoung
   Shmueli, Ron B.
   Lorenc, Valeria E.
   Fortmann, Seth D.
   Sciamanna, Jason
   Pandey, Niranjan B.
   Green, Jordan J.
   Popel, Aleksander S.
   Campochiaro, Peter A.
TI Tyrosine kinase blocking collagen IV-derived peptide suppresses ocular
   neovascularization and vascular leakage
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC MACULAR EDEMA; PRO-PERMEABILITY
   FACTORS; RETINAL VEIN OCCLUSION; CHOROIDAL NEOVASCULARIZATION;
   TUMOR-GROWTH; SUBRETINAL NEOVASCULARIZATION; FACTOR RECEPTOR-2; FACTOR
   THERAPY; VEGF
AB Vascular endothelial growth factor (VEGF)-neutralizing proteins provide benefit in several retinal and choroidal vascular diseases, but some patients still experience suboptimal outcomes, and the need for frequent intraocular injections is a barrier to good outcomes. A mimetic peptide derived from collagen IV, AXT107, suppressed subretinal neovascularization (NV) in two mouse models predictive of effects in neovascular age-related macular degeneration (NVAMD) and inhibited retinal NV in a model predictive of effects in ischemic retinopathies. A combination of AXT107 and the current treatment aflibercept suppressed subretinal NV better than either agent alone. Furthermore, AXT107 caused regression of choroidal NV. AXT107 reduced the VEGF-induced vascular leakage that underlies macular edema in ischemic retinopathies and NVAMD. In rabbit eyes, which are closer to the size of human eyes, intraocular injection of AXT107 significantly reduced VEGF-induced vascular leakage by 86% at 1 month and 70% at 2 months; aflibercept significantly reduced leakage by 69% at 1 month and did not reduce leakage at 2 months, demonstrating the longer effectiveness of AXT107. AXT107 reduced ligand-induced phosphorylation of multiple receptors: VEGFR2, c-Met, and PDGFR beta. Optimal signaling through these receptors requires complex formation with beta(3) integrin, which was reduced by AXT107 binding to alpha(v)beta(3). AXT107 also reduced total VEGFR2 levels by increasing internalization, ubiquitination, and degradation. This biomimetic peptide is a sustained, multitargeted therapy that may provide advantages over intraocular injections of specific VEGF-neutralizing proteins.
C1 [Lima e Silva, Raquel; Kanan, Yogita; Lorenc, Valeria E.; Fortmann, Seth D.; Sciamanna, Jason; Green, Jordan J.; Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
   [Lima e Silva, Raquel; Kanan, Yogita; Lorenc, Valeria E.; Fortmann, Seth D.; Sciamanna, Jason; Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
   [Mirando, Adam C.; Kim, Jayoung; Shmueli, Ron B.; Pandey, Niranjan B.; Green, Jordan J.; Popel, Aleksander S.] Johns Hopkins Univ, Dept Biomed Engn, Dept Neurosci, Baltimore, MD 21205 USA.
   [Kim, Jayoung; Shmueli, Ron B.; Green, Jordan J.] Johns Hopkins Univ, Sch Med, Translat Tissue Engn Ctr, Baltimore, MD 21205 USA.
   [Pandey, Niranjan B.] AsclepiX Therapeut LLC, Baltimore, MD 21211 USA.
   [Green, Jordan J.] Johns Hopkins Univ, Sch Med, Inst Nanobiotechnol, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins
   University; Johns Hopkins University; Johns Hopkins University
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.; Campochiaro, PA (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
EM pcampo@jhmi.edu
RI Popel, Aleksander S/A-6724-2009; Green, Jordan/B-9001-2009
OI Green, Jordan/0000-0003-4176-3808; Fortmann, Seth/0000-0002-9554-8751;
   Popel, Aleksander/0000-0002-6706-9235
FU Edward N. and Della L. Thome Memorial Foundation (Cambridge, MA); NIH
   NEI [R21EY022986, R21EY026148, 1R43EY024495, 1R43EY025903]; Maryland
   Biotechnology Award; TEDCO Maryland Innovation Initiative; Johns
   Hopkins-Coulter Translational Partnership; NATIONAL EYE INSTITUTE
   [R43EY024495, R21EY026148, R43EY025903, R21EY022986] Funding Source: NIH
   RePORTER
FX This work was supported by a grant from the Edward N. and Della L. Thome
   Memorial Foundation (Cambridge, MA); NIH NEI grants R21EY022986,
   R21EY026148, 1R43EY024495, and 1R43EY025903; Maryland Biotechnology
   Award and TEDCO Maryland Innovation Initiative Phases 1 and 3; and the
   Johns Hopkins-Coulter Translational Partnership.
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NR 57
TC 33
Z9 35
U1 3
U2 17
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JAN 18
PY 2017
VL 9
IS 373
AR eaai8030
DI 10.1126/scitranslmed.aai8030
PG 11
WC Cell Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA EL2JX
UT WOS:000394447000005
PM 28100839
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Li, FL
   Zeng, YX
   Xu, HW
   Yin, ZQ
AF Li, Fuliang
   Zeng, Yuxiao
   Xu, Haiwei
   Yin, Zheng Qin
TI Subretinal transplantation of retinal pigment epithelium overexpressing
   fibulin-5 inhibits laser-induced choroidal neovascularization in rats
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Choroidal neovascularization;
   Fibulin-5; Retinal pigment epithelium; Transplantation
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; ROYAL-COLLEGE; FACTOR
   VEGF; STEM-CELLS; IN-VIVO; RPE; EXPRESSION; PROLIFERATION; ANGIOGENESIS
AB Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Choroidal neovascularization (CNV) is the abnormal angiogenesis that causes severe visual loss in AMD. Fibulin-5 (Fbln5), which functions as an angiogenesis inhibitor, plays an important role in the pathogenesis of AMD. Here, we investigated whether subretinal transplantation of Fbln5-overexpressing retinal pigment epithelial (RPE) cells can inhibit CNV in vivo. Adult Long-Evans rats were used in this study. CNV was induced by laser photocoagulation. One week after laser-induced CNV, RPE cells expressing pZlen-Fbln5-IRES-GFP or the control pZlen-IRES-GFP vectors were transplanted into the subretinal space of the right and left eyes, respectively. CNV was evaluated using fundus photography, fundus fluorescein angiography (FFA), and hematoxylin and eosin staining. We found that CNV occurred at 1 week after photocoagulation, reaching peak activity at 3 weeks and remaining at a high level at 4-5 weeks after photocoagulation. Transplanted RPE cells survived for at least 4 weeks and migrated toward the retina. Subretinal transplantation of Fbln5-overexpressing RPE cells resulted in a significant reduction in the total area of leakage and the number of leakage spots compared with transplantation of RPE cells expressing only green fluorescent protein. Our findings suggest that subretinal transplantation of Fbln5-overexpressing RPE cells inhibits laser-induced CNV in rats and thus represents a promising therapy for the treatment of AMD. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Li, Fuliang; Zeng, Yuxiao; Xu, Haiwei; Yin, Zheng Qin] Third Mil Med Univ, Southwest Hosp, Southwest Eye Hosp, Chongqing, Peoples R China.
   [Li, Fuliang; Zeng, Yuxiao; Xu, Haiwei; Yin, Zheng Qin] Key Lab Visual Damage & Regenerat & Restorat Chon, Chongqing, Peoples R China.
C3 Army Medical University
RP Xu, HW (通讯作者)，Southwest Eye Hosp, 30 Gaotanyan St, Chongqing 400038, Peoples R China.
EM haiweixu2001@163.com; qinzyin@aliyun.com
OI Li, Fuliang/0000-0001-8002-1298
FU National Basic Research Program of China [2013CB967002]; National
   Natural Science Foundation of China [30801270]
FX We thank Shujia Huo, Jing Xie, Yaochen Li, Chuanhuang Weng, and Jianrong
   He for their excellent technical support. This work was supported by
   National Basic Research Program of China (No. 2013CB967002).and National
   Natural Science Foundation of China (No. 30801270).
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NR 36
TC 10
Z9 11
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 JUL
PY 2015
VL 136
BP 78
EP 85
DI 10.1016/j.exer.2015.05.004
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CK9LR
UT WOS:000356562100010
PM 25983185
DA 2022-11-30
ER

PT J
AU Krohne, TU
   Kaemmerer, E
   Holz, FG
   Kopitz, J
AF Krohne, Tim U.
   Kaemmerer, Elke
   Holz, Frank G.
   Kopitz, Juergen
TI Lipid peroxidation products reduce lysosomal protease activities in
   human retinal pigment epithelial cells via two different mechanisms of
   action
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; retinal pigment epithelium; lysosome;
   cathepsin; outer segments; oxidative stress; lipid peroxidation; cell
   culture
ID HUMAN GASTRIC LIPASE; CATHEPSIN-D; MACULAR DEGENERATION; OXIDATIVE
   STRESS; ESTER HYDROLASE; OUTER SEGMENTS; RPE; PATHOGENESIS; LIPOFUSCIN;
   PROTEINS
AB In age-related macular degeneration (AMD), reduced lysosomal capacity may contribute to lipofuscinogenesis and progressive dysfunction of the retinal pigment epithelium (RPE). We previously demonstrated that lipid peroxidation-related protein modifications inhibit lysosomal degradation of photoreceptor outer segment (POS) proteins in RPE cells. Herein, we investigate the effects of lipid peroxidation products on activities of key RPE lysosomal proteases. In lysosomes isolated from primary human RPE cells, lipid peroxidation products 4-hydroxynonenal (HNE) and malondialdehyde (MDA) exerted a dose-dependent inhibitory effect on cysteine proteases cathepsin B and L, with biologically relevant concentrations of I AM resulting in a reduction of enzyme activities by 88-94%. This effect was confirmed in cultured RPE cells. Using mass spectrometry, covalent HNE and MDA adducts were detected in the active center region of inactivated cathepsins. POS previously modified with HNE and MDA likewise caused a dose-dependent reduction of cathepsin B and L activities in isolated lysosomes and, in addition, inhibited the aspartic protease cathepsin D. Our results indicate that lipid peroxidation products in vitro interfere with RPE lysosomal protease activities by two different mechanisms of action: (i) HNE and MDA directly inactivate lysosomal cysteine proteases by covalent binding to the active center; (ii) HNE- and MDA-mediated protein modifications convert proteolytic substrates into competitive inhibitors of lysosomal proteases. Via these mechanisms, lipid peroxidation products may induce lysosomal dysfunction and lipofuscinogenesis in the aging RPE and thus contribute to the pathogenesis of AMD. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Krohne, Tim U.; Holz, Frank G.] Univ Bonn, Dept Ophthalmol, D-5300 Bonn, Germany.
   [Kaemmerer, Elke; Kopitz, Juergen] Univ Heidelberg, Dept Mol Pathol, Heidelberg, Germany.
C3 University of Bonn; Ruprecht Karls University Heidelberg
RP Krohne, TU (通讯作者)，Univ Eye Hosp, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM krohne@uni-bonn.de
RI Krohne, Tim/D-1497-2013; Krohne, Tim/AAG-4412-2020
OI Krohne, Tim/0000-0003-2280-925X; 
FU German Research Foundation [2863/6-1]; DFG Priority Program "Age-related
   macular degeneration" [KO 1663/2-3 UK, HO 1926/2-1 UK]; University of
   Bonn BONFOR Program; Dr. Eberhard und Hilde Rbdiger Foundation;  [1088]
FX This study was supported by the German Research Foundation (DFG), grant
   KR 2863/6-1 (TUK); DFG Priority Program "Age-related macular
   degeneration" (SPP 1088), grants KO 1663/2-3 UK) and HO 1926/2-1 UK,
   FGH); the University of Bonn BONFOR Program, Gerok Fellowship (TUK); and
   the Dr. Eberhard und Hilde Rbdiger Foundation (TUK).
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NR 36
TC 71
Z9 75
U1 1
U2 10
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2010
VL 90
IS 2
BP 261
EP 266
DI 10.1016/j.exer.2009.10.014
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 557AG
UT WOS:000274639100011
PM 19895809
DA 2022-11-30
ER

PT J
AU Artunay, O
   Yuzbasioglu, E
   Rasier, R
   Sengul, A
   Bahcecioglu, H
AF Artunay, O.
   Yuzbasioglu, E.
   Rasier, R.
   Sengul, A.
   Bahcecioglu, H.
TI Incidence and management of acute endophthalmitis after intravitreal
   bevacizumab (Avastin) injection
SO EYE
LA English
DT Article
DE intravitreal injection; bevacizumab; endophthalmitis
ID COHERENCE TOMOGRAPHY FINDINGS; POSTOPERATIVE ENDOPHTHALMITIS;
   MOXIFLOXACIN 0.5-PERCENT; OPHTHALMIC SOLUTION; SAFETY; INFLAMMATION;
   RANIBIZUMAB; PENETRATION; VANCOMYCIN; VITRECTOMY
AB Introduction The aim of this study was to report the incidence and management of acute endophthalmitis after intravitreal injection of Avastin (bevacizumab), and visual acuity outcomes of three eyes of three patients who developed acute endophthalmitis following intravitreal injection of Avastin.
   Methods This clinical retrospective, non-comparative study included 3022 intravitreal injections of 1.25 mg bevacizumab consecutively performed for 1822 eyes with exudative age-related macular degeneration and other retinal diseases. Of 3022 injections, 1200 were reinjections. After clinical appearance of post-injection endophthalmitis, immediate intervention was performed, including injection of intravitreal antibiotics and early pars plana vitrectomy.
   Results Three eyes of three patients with acute postoperative endophthalmitis were identified in the first week following intravitreal injections of 1.25 mg bevacizumab. Among of these patients, two cases were culture-positive and one case was culture-negative. Compared with presenting visual acuities, all of three patients improved at the end of follow-up time. The overall incidence rate of post-injection culture-proven endophthalmitis was 0.066%.
   Discussion Acute culture-proven endophthalmitis is still a potential complication of intravitreal bevacizumab injection (approximately 0.066%) despite using maximal sterile techniques. Acute post-injection endophthalmitis following intravitreal bevacizumab occurs rapidly and can result in severe loss of vision. Prompt recognition and treatment are key in maximizing outcomes in patients who developed endophthalmitis after intravitreal injection of bevacizumab. Eye (2009) 23, 2187-2193; doi:10.1038/eye.2009.7; published online 13 February 2009
C1 [Artunay, O.; Yuzbasioglu, E.; Rasier, R.; Sengul, A.; Bahcecioglu, H.] Istanbul Bilim Univ, Dept Ophthalmol, Istanbul, Turkey.
C3 Demiroglu Bilim University
RP Artunay, O (通讯作者)，Sisli Florence Nightingale Hastanesi, Abidei Hurriyet Sok 1, Istanbul, Turkey.
EM artunay@gmail.com
RI Rasier, Rifat/AHB-8857-2022; Rasier, Rifat/AAK-4259-2021
OI Rasier, Rifat/0000-0003-0963-7991; 
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NR 39
TC 55
Z9 59
U1 2
U2 7
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 DEC
PY 2009
VL 23
IS 12
BP 2187
EP 2193
DI 10.1038/eye.2009.7
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 530JK
UT WOS:000272585500007
PM 19218994
OA Bronze
DA 2022-11-30
ER

PT J
AU Wirostko, B
   Wong, TY
   Simo, R
AF Wirostko, Barbara
   Wong, Tien Y.
   Simo, Rafael
TI Vascular endothelial growth factor and diabetic complications
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Vascular endothelial growth factor; Diabetes mellitus; Diabetic
   retinopathy; Diabetic angiopathies; Vascular endothelial growth factor;
   receptors; Angiogenesis inhibitors; Microvascular disease;
   Cardiovascular disease; Stroke
ID RETINAL MICROVASCULAR ABNORMALITIES; FACTOR GENE-EXPRESSION; NEONATAL
   FC-RECEPTOR; PROGENITOR CELLS; NITRIC-OXIDE; FACTOR VEGF;
   ATHEROSCLEROSIS RISK; VITREOUS LEVELS; OCULAR NEOVASCULARIZATION;
   INTRAMYOCARDIAL INJECTION
AB Intraocular delivery of anti-vascular endothelial growth factor (VEGF) therapies is now used widely to treat age-related macular degeneration, and is currently undergoing evaluation in clinical trials for treatment of diabetic retinopathy. An important aspect of anti-VEGF treatment is that while the agents are injected into the vitreous cavity, they may be absorbed systemically, thus potentially affecting systemic VEGF levels. Systemic VEGF-A and the interplay between membrane-bound VEGF receptors and the soluble form of VEGF-RI are key to angiogenesis, vasculogenesis, neurogenesis and hemodynamics. These cellular processes are regulated by complicated negative and positive feedback loops, many of which are disrupted and altered in diabetes. The VEGF protein, mRNA, as well as the actual VEGF receptor levels, appear to be impaired in diabetes in microvascular and macrovascular vessel beds. What is not clear is the exact role and influence that these levels have on an organ's function. In some organ systems, elevated VEGF levels act as a pathologic angiogenic stimulus (i.e., ocular neovascularization) whereas in others, low levels of VEGF activity leads to pathology (i.e., cardiomyopathy, wound healing and peripheral neuropathy). Diabetic patients have a higher risk of hypertension and proteinuria, two surrogate markers of systemic VEGF inhibition. Certain intraocular anti-VEGF treatments could therefore have an adverse effect in this population by possibly affecting circulating and organ-specific VEGF and VEGF receptor levels. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Wong, Tien Y.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.
   [Wirostko, Barbara] Pfizer Inc, New York, NY USA.
   [Simo, Rafael] Univ Autonoma Barcelona, CIBERDEM ISCIII, E-08193 Barcelona, Spain.
   [Simo, Rafael] Univ Autonoma Barcelona, Inst Recerca, Hosp Univ Vall Hebron, Diabet & Metab Res Unit, E-08193 Barcelona, Spain.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; Pfizer; Autonomous University of Barcelona;
   CIBER - Centro de Investigacion Biomedica en Red; CIBERDEM; Autonomous
   University of Barcelona; Hospital Universitari Vall d'Hebron; Vall
   d'Hebron Institut de Recerca (VHIR)
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 Wong, Tien Yin/AAC-9724-2020
OI Wong, Tien Yin/0000-0002-8448-1264; Simo Canonge,
   Rafael/0000-0003-0475-3096
FU KRF Research; Xtec Media, Inc; Pfizer Inc, New York, New York
FX Editorial assistance including literature search and evaluation,
   contributing to the first draft of the manuscript, revision of the paper
   based on author feedback, and styling the paper for journal submission
   was provided by Pat Ray Reese, PhD of Reese Associates Consulting LLC.
   Kelley R. Friel, MA of KRF Research, Writing and Editing Services
   assisted with copy editing. Christopher Yee, of Xtec Media, Inc.,
   assisted with the figures. Editorial support was funded by Pfizer Inc,
   New York, New York.
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NR 157
TC 156
Z9 163
U1 2
U2 30
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 NOV
PY 2008
VL 27
IS 6
BP 608
EP 621
DI 10.1016/j.preteyeres.2008.09.002
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 382RS
UT WOS:000261623700003
PM 18929676
DA 2022-11-30
ER

PT J
AU Theogarajan, LS
AF Theogarajan, Luke S.
TI A Low-Power Fully Implantable 15-Channel Retinal Stimulator Chip
SO IEEE JOURNAL OF SOLID-STATE CIRCUITS
LA English
DT Article
DE Adaptive bandwidth; amplitude shift keyed (ASK); delay-locked loop
   (DLL); retinal prosthesis; self-biased; single-differential
ID IRIDIUM OXIDE; CMOS; CIRCUIT; CHARGE
AB Retinal prostheses are being developed around the world in hopes of restoring useful vision for patients suffering from certain types of diseases like age-related macular degeneration (AMD) and retinitis pigmentosa. The central component of an electrical retinal prosthesis is a wirelessly powered and driven stimulator chip. The chip receives commands from the outside and outputs biphasic current pulses to an electrode array placed in the retina that stimulate the remaining retinal neurons. The chip contains 30 000 transistors in a 0.5 mu m technology (two-poly three-metal, 2P3M), occupies an area of 2.3 mm x 2.3 mm, and excluding the current sources consumes less than 2 mW of power. The chip is powered inductively via a 125 kHz power signal which is rectified to generate a +/- 2.5 V supply. The data signal is transmitted as an amplitude shift keyed (ASK) signal on a 13.56 MHz carrier. The data rate can be varied from 25 to 714 kHz and the symbol (0 or 1) is encoded as the pulse width of the data signal. A self-biased feedback-loop-based single-to-differential converter restores the signal to full rail levels. Clock and data recovery is performed by a self-biased low-power inverter-based delay-locked loop (DLL). The chip can receive four commands, and each command is 16 bits long. The current amplitude, pulse duration, and inter-pulse duration can be programmed by using the four commands.
C1 Univ Calif Santa Barbara, Dept Elect & Comp Engn, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara
RP Theogarajan, LS (通讯作者)，Univ Calif Santa Barbara, Dept Elect & Comp Engn, Santa Barbara, CA 93106 USA.
EM ltheogar@ece.ucsb.edu
RI Theogarajan, Luke/AAS-5260-2021
FU Catalyst Foundation
FX This work was supported by the Catalyst Foundation. Chip fabrication was
   provided by MOSIS.
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NR 29
TC 60
Z9 63
U1 0
U2 7
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9200
EI 1558-173X
J9 IEEE J SOLID-ST CIRC
JI IEEE J. Solid-State Circuit
PD OCT
PY 2008
VL 43
IS 10
BP 2322
EP 2337
DI 10.1109/JSSC.2008.2004331
PG 16
WC Engineering, Electrical & Electronic
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA 363FF
UT WOS:000260252500016
DA 2022-11-30
ER

PT J
AU Kumar, A
   Gopalakrishnan, K
   Sinha, S
AF Kumar, Atul
   Gopalakrishnan, Kiran
   Sinha, Subijoy
TI Combination photodynamic therapy and intravitreal ranibizumab in
   neovascular AMD in a north Indian population - A pilot study
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; CHOROIDAL
   NEOVASCULARIZATION; VERTEPORFIN; PREVALENCE; TRIAMCINOLONE
AB Purpose: To evaluate photodynamic therapy (PDT) with verteporfin along with intravitreal Ranibizumab in treatment of neovascular age related macular degeneration.
   Methods: This prospective interventional care series included 16 patients (17 eyes) of choroidal neovascularization secondary to neovascular AMD, who were treated with PDT with verteporfin followed by an injection of 0.5mg Ranibuzimab on the same day. The main outcome measures were best corrected visual acuity (VA) as recorded by both Snellen's and ETDRS charts (logMAR), contrast sensitivity (Pelli-Robson Chart), retreatment frequency and frequency of side effects.
   Results: Seventeen eyes underwent PDT with verteporfin and intravitreal 0.5mg Ranibizumab, following PDT. Patients were followed up every month for a total period of 6 months. Initial VA ranged from CF to 20/32 and final acuity ranged from CF to 20/20. VA stabilizes (gain/loss <2 lines) in 14 out of 17 eyes (82.24%) and improved in 3 out of 17 (17.65%). Contrast sensitivity improved in 15 out of 17 eyes (82.24%) Lesion type, patient age had no influence on the outcome. There were no cases of ocular/systematic adverse events. Retreatment was required in only 2 out of 17 cases (11.76%) with only a single injection of ranibizumab.
   Conclusion: The combination of PDT with intravitreal Ranibizumab improves contrast sensitivity and stabilizes vision and reduces the number of retreatments, without significant ocular and/or systematic risks.
C1 [Kumar, Atul; Gopalakrishnan, Kiran; Sinha, Subijoy] All India Inst Med Sci, New Delhi 110021, India.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi
RP Kumar, A (通讯作者)，All India Inst Med Sci, D-66,Malcha Marg, New Delhi 110021, India.
EM akum66mm@yahoo.co.in
RI Gopalakrishnan, Kiran/AAL-1487-2021
CR Arnold J, 2001, AM J OPHTHALMOL, V131, P541
   Blick SKA, 2007, DRUGS, V67, P1199, DOI 10.2165/00003495-200767080-00007
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NR 19
TC 10
Z9 10
U1 1
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 SEP
PY 2008
VL 28
IS 8
BP 1132
EP 1137
DI 10.1097/IAE.0b013e318170d76d
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 350CC
UT WOS:000259329100015
PM 18779720
DA 2022-11-30
ER

PT J
AU Gass, JDM
   Agarwal, A
   Lavina, AM
   Tawansy, KA
AF Gass, JDM
   Agarwal, A
   Lavina, AM
   Tawansy, KA
TI Focal inner retinal hemorrhages in patients with drusen - An early sign
   of occult choroidal neovascularization and chorioretinal anastomosis
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; occult chorioretinal vascular
   anastomosis; occult choroidal neovascularization; retinal pigment
   epithelium detachment; drusen; laser photocoagulation; superficial
   retinal hemorrhage; type 1 subretinal pigment epithelial; choroidal
   neovascularization; type 2 subsensory retinal choroidal
   neovascularization
ID MACULAR DEGENERATION; ANGIOMATOUS PROLIFERATION; DETACHMENTS
AB Purpose: To present evidence that superficial retinal hemorrhage in the macula of patients with age-related macular degeneration (ARMD) may be an early sign of occult chorioretinal anastomosis (OCRA) and type 1 occult choroidal neovascularization (OCNV).
   Methods: Retrospective follow-up study of 16 patients presenting with a small focal area of superficial retinal hemorrhages and drusen in the juxtafoveolar area in 24 eyes.
   Results: OCRA and OCNV occurred in an older subset of patients with ARMD (mean age, 75 years). Of 22 eyes with the early stages of chorioretinal anastomosis (CRA), 18 had evidence of a piggyback neovascular complex, with the smaller subsensory retinal type 2 complex lying anterior to the larger subretinal pigment epithelial type 1 complex. At initial presentation, three patients had OCRA and OCNV bilaterally, and three patients had large disciform cicatricial lesions with overt CRA in the fellow eye. Nine patients had one or more laser photocoagulation treatments for early stages of CRA. Only one patient maintained visual acuity of better than 20/200 for >1 year. At the last follow-up, 24 of 26 eyes with CRA had visual acuity of 20/200 or less.
   Conclusion: Superficial retinal hemorrhage in the paracentral area of patients with drusen is the earliest sign of OCRA and OCNV. Fluorescein angiography and indocyanine green angiography are important in detecting the dual nature of the subretinal neovascular network. Photocoagulation and photodynamic treatment is usually unsuccessful in preserving central vision.
C1 Vanderbilt Univ, Sch Med, Vanderbilt Eye Ctr, Dept Ophthalmol, Nashville, TN 37232 USA.
   Univ British Columbia, Dept Ophthalmol, Vancouver, BC V5Z 1M9, Canada.
   Childrens Hosp, Dept Ophthalmol, Los Angeles, CA 90027 USA.
C3 Vanderbilt University; University of British Columbia; Children's
   Hospital Los Angeles
RP Gass, JDM (通讯作者)，Vanderbilt Univ, Sch Med, Vanderbilt Eye Ctr, Dept Ophthalmol, 8010 Med Ctr E, Nashville, TN 37232 USA.
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NR 13
TC 128
Z9 134
U1 0
U2 2
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 2003
VL 23
IS 6
BP 741
EP 751
DI 10.1097/00006982-200312000-00001
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 759FR
UT WOS:000187728100001
PM 14707822
DA 2022-11-30
ER

PT J
AU Hioka, N
   Chowdhary, RK
   Chansarkar, N
   Delmarre, D
   Sternberg, E
   Dolphin, D
AF Hioka, N
   Chowdhary, RK
   Chansarkar, N
   Delmarre, D
   Sternberg, E
   Dolphin, D
TI Studies of a benzoporphyrin derivative with Pluronics
SO CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE
LA English
DT Article
DE Pluronic; poloxamers; block copolymers; photosensitizing drug;
   photodynamic therapy (PDT); formulation; micelles
ID PHOTODYNAMIC THERAPY; AQUEOUS-SOLUTIONS; AGGREGATION; PHOTOSENSITIZERS;
   THERMODYNAMICS; SURFACTANTS; COPOLYMERS; PORPHYRINS; DYNAMICS; BPD
AB The synthetic route for the benzoporphyrin derivatives produces two regioisomers in equimolar quantities (ring A and B isomers). A derivative of the A-ring product, BPD-MA (benzoporphyrin-derivative monoacid ring A, verteporfin), has recently been approved in North America and Europe for the treatment of age-related macular degeneration. The B-ring isomers, contrary to the A-ring isomers, exhibit high aggregation in many formulations, which results in inadequate drug delivery for clinical uses. To avoid aggregation, a non-ionic surfactant polymer such as a Pluronic - poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) - may be used as a formulation excipient. The triblock polymer investigated here is designated P123 (or poloxamer 403). When used to formulate a monoacid benzoporphyrin B-ring derivative (2), a critical micelle concentration of P123 in water occurred at approximately 0.015 to 0.03%. The apparent pK(a) of compound 2 was dependent on its concentration in P123, and decreased as the molar ratio (P123:2) increased. High concentrations of P123 and neutral pH were found to be the best conditions to maintain the drug in its monomeric form. Kinetic studies suggest that the aggregate of 2 contains several molecules, and is formed by a catalyzed self-assembly process. Samples with 1 mg mL(-1) of drug, at pH = 7.4, and 4.8% of Pluronic showed satisfactory capacity to load and keep monomers stable. This formulation has potential PDT applications.
C1 Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada.
   Univ Estadual Maringa, Dept Quim, Maringa, Parana, Brazil.
C3 University of British Columbia; Universidade Estadual de Maringa
RP Dolphin, D (通讯作者)，Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
RI Hioka, Noboru/H-3111-2012
OI Hioka, Noboru/0000-0002-5089-9734; Hioka, Noboru/0000-0003-0775-5839
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NR 22
TC 47
Z9 47
U1 1
U2 18
PU NATL RESEARCH COUNCIL CANADA
PI OTTAWA
PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA
SN 0008-4042
J9 CAN J CHEM
JI Can. J. Chem.-Rev. Can. Chim.
PD OCT
PY 2002
VL 80
IS 10
BP 1321
EP 1326
DI 10.1139/V02-167
PG 6
WC Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry
GA 623LC
UT WOS:000179703700007
DA 2022-11-30
ER

PT J
AU Jung, JH
   Kim, SS
   Chung, HYW
   Hejri, A
   Prausnitz, MR
AF Jung, Jae Hwan
   Kim, Seong Shik
   Chung, Hyunwoo
   Hejri, Amir
   Prausnitz, Mark R.
TI Six-month sustained delivery of anti-VEGF from in-situ forming hydrogel
   in the suprachoroidal space
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Anti-VEGF; In-situ forming hydrogel; Microneedles; Posterior ocular
   disease; Suprachoroidal injection
ID DRUG-DELIVERY; CONTROLLED-RELEASE; BEVACIZUMAB; PHARMACOKINETICS;
   CLEARANCE; EFFICACY; FORMULATIONS; RANIBIZUMAB; INJECTION; MOLECULES
AB Patients with wet age-related macular degeneration (AMD) require intravitreal injections of bevacizumab (Bev) or other drugs, often on a monthly basis, which is a burden on the healthcare system. Here, we developed an in -situ forming hydrogel comprised of Bev and hyaluronic acid (HA) crosslinked with poly(ethylene glycol) dia-crylate for slow release of Bev after injection into the suprachoroidal space (SCS) of the eye using a microneedle. Liquid Bev formulations were cleared from SCS within 5 days, even when formulated with high viscosity, unless Bev was conjugated to a high molecular-weight HA (2.6 MDa), which delayed clearance until 1 month. To extend release to 6 months, we synthesized in-situ forming Bev-HA hydrogel initially as a low-viscosity mixture suitable for injection and flow in the SCS to cover a large area extending to the posterior pole of the eye where the macula is located in humans. Within 1 h after injection, Bev and HA were crosslinked, which retained Bev for slow release as the hydrogel biodegraded. In vivo studies in the rabbit eye reported Bev release for >6 months, depending on gel formulation and Bev assay. The in-situ forming Bev-HA hydrogel was well tolerated, as assessed by clinical exam, fundus imaging, histological analysis, and intraocular pressure measurement. We conclude that Bev released from an in-situ forming hydrogel may enable long-acting treatments of AMD and other posterior ocular indications.
C1 [Jung, Jae Hwan; Kim, Seong Shik; Chung, Hyunwoo; Hejri, Amir; Prausnitz, Mark R.] Georgia Inst Technol, Sch Chem & Biomol Engn, Atlanta, GA 30332 USA.
   [Jung, Jae Hwan] Dankook Univ, Dept Pharmaceut Engn, Yongin, South Korea.
C3 University System of Georgia; Georgia Institute of Technology; Dankook
   University
RP Prausnitz, MR (通讯作者)，Georgia Inst Technol, Sch Chem & Biomol Engn, Atlanta, GA 30332 USA.
EM prausnitz@gatech.edu
FU National Institutes of Health [R01EY022097, R01EY025286]
FX Acknowledgements The authors thank Dr. Laura O?Farrell and Dr. Richard
   Noel for help with animal studies and Donna Bondy for administrative
   support. This work was supported by grants from the National Institutes
   of Health (R01EY022097 and R01EY025286) .
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NR 59
TC 0
Z9 0
U1 11
U2 11
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD DEC
PY 2022
VL 352
BP 472
EP 484
DI 10.1016/j.jconrel.2022.10.036
PG 13
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Pharmacology & Pharmacy
GA 6D2MM
UT WOS:000882531400005
PM 36309098
DA 2022-11-30
ER

PT J
AU Kuang, TMT
   Xirasagar, S
   Lee, WY
   Cheng, YF
   Kuo, NW
   Lin, HC
AF Kuang, Tung-Mei Tammy
   Xirasagar, Sudha
   Lee, Wei-Yun
   Cheng, Yen-Fu
   Kuo, Nai-Wen
   Lin, Herng-Ching
TI Absence of an Association between Macular Degeneration and Young-Onset
   Dementia
SO JOURNAL OF PERSONALIZED MEDICINE
LA English
DT Article
DE young onset dementia; macular degeneration; epidemiology
ID CARDIOVASCULAR-HEALTH; COGNITIVE FUNCTION; AGE; PREVALENCE; RISK;
   SUBTYPES; DISEASE; SMOKING; MIDLIFE; PEOPLE
AB A few population-based studies have reported an association between prior age-related macular degeneration and senile dementia. No study has explored a possible link between prior macular degeneration and young-onset dementia (YOD). This case-control study aimed to evaluate the association of YOD with prior macular degeneration diagnosed in the 5-year period before their index date. Data for this retrospective observational study were retrieved from Taiwan's National Health Insurance (NHI) dataset. A total of 36,577 patients with newly diagnosed YOD from January 2010 to December 2017 were identified as the study cohort, assigning their diagnosis date as their index date. Comparison patients were identified by propensity score-matching (three per case, n = 109,731 controls) from the remaining NHI beneficiaries of the period, their index date being the date of their first ambulatory care claim in the year of diagnosis of their matched YOD case. Chi-square test revealed no significant difference in the prevalence of prior macular degeneration between cases and controls (1.1% vs. 1.0%, p = 0.111). Conditional logistic regression analysis also showed an unadjusted odds ratio (OR) for prior macular degeneration of 1.098 among cases relative to controls (95% CI: 0.9797-1.232). Adjusted analysis confirmed that YOD was not associated with prior macular degeneration, adjusted odds ratio 1.098 (95% CI = 0.979-1.232). We conclude that patients with macular degeneration are not at increased risk for YOD.
C1 [Kuang, Tung-Mei Tammy] Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei 112, Taiwan.
   [Kuang, Tung-Mei Tammy] Natl Yang Ming Chiao Tung Univ, Sch Med, Dept Ophthalmol, Taipei 112, Taiwan.
   [Kuang, Tung-Mei Tammy] Taipei Med Univ, Coll Med, Res Ctr Sleep Med, Taipei 110, Taiwan.
   [Xirasagar, Sudha] Univ South Carolina, Arnold Sch Publ Hlth, Dept Hlth Serv Policy & Management, Columbia, SC 29208 USA.
   [Lee, Wei-Yun; Kuo, Nai-Wen; Lin, Herng-Ching] Taipei Med Univ, Coll Management, Sch Hlth Care Adm, Taipei 110, Taiwan.
   [Cheng, Yen-Fu] Taipei Vet Gen Hosp, Dept Med Res, Taipei 112, Taiwan.
   [Cheng, Yen-Fu] Taipei Vet Gen Hosp, Dept Otolaryngol Head & Neck Surg, Taipei 112, Taiwan.
   [Cheng, Yen-Fu] Natl Yang Ming Chiao Tung Univ, Dept Otolaryngol Head & Neck Surg, Sch Med, Taipei 112, Taiwan.
   [Lin, Herng-Ching] Taipei Med Univ Hosp, Sleep Res Ctr, Taipei 110, Taiwan.
C3 Taipei Veterans General Hospital; National Yang Ming Chiao Tung
   University; Taipei Medical University; University of South Carolina
   System; University of South Carolina Columbia; Taipei Medical
   University; Taipei Veterans General Hospital; Taipei Veterans General
   Hospital; National Yang Ming Chiao Tung University; Taipei Medical
   University; Taipei Medical University Hospital
RP Lin, HC (通讯作者)，Taipei Med Univ, Coll Management, Sch Hlth Care Adm, Taipei 110, Taiwan.; Lin, HC (通讯作者)，Taipei Med Univ Hosp, Sleep Res Ctr, Taipei 110, Taiwan.
EM kuangtammy@gmail.com; sxirasagar@sc.edu; m911108007@tmu.edu.tw;
   entist@gmail.com; nwkuo@tmu.edu.tw; henry11111@tmu.edu.tw
OI Lin, Herng-Ching/0000-0003-4661-959X; KUO, NAI-WEN/0000-0001-9199-2882
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NR 43
TC 0
Z9 0
U1 2
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2075-4426
J9 J PERS MED
JI J. Pers. Med.
PD FEB
PY 2022
VL 12
IS 2
AR 291
DI 10.3390/jpm12020291
PG 10
WC Health Care Sciences & Services; Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services; General & Internal Medicine
GA ZK0KY
UT WOS:000762687600001
PM 35207778
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ma, X
   Takahashi, Y
   Wu, WJ
   Liang, WT
   Chen, JL
   Chakraborty, D
   Li, YX
   Du, YH
   Benyajati, S
   Ma, JX
AF Ma, Xiang
   Takahashi, Yusuke
   Wu, Wenjing
   Liang, Wentao
   Chen, Jianglei
   Chakraborty, Dibyendu
   Li, Yangxiong
   Du, Yanhong
   Benyajati, Siribhinya
   Ma, Jian-Xing
TI ADAM17 mediates ectodomain shedding of the soluble VLDL receptor
   fragment in the retinal epithelium
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DENSITY-LIPOPROTEIN RECEPTOR; WNT SIGNALING PATHWAY; PATHOGENIC ROLE;
   EXPRESSION; METALLOPROTEINASE; DEGENERATION; INFLAMMATION
AB Very low-density lipoprotein receptor (VLDLR) is a multi-functional transmembrane protein. Beyond the function of the full-length VLDLR in lipid transport, the soluble ectodomain of VLDLR (sVLDLR) confers anti-inflammatory and anti-angiogenic roles in ocular tissues through inhibition of canonical Wnt signaling. However, it remains unknown how sVLDLR is shed into the extracellular space. In this study, we present the first evidence that a disintegrin and metalloprotease 17 (ADAM17) is responsible for sVLDLR shedding in human retinal pigment epithelium cells using pharmacological and genetic approaches. Among selected proteinase inhibitors, an ADAM17 inhibitor demonstrated the most potent inhibitory effect on sVLDLR shedding. siRNA-mediated knockdown or CRISPR/Cas9-mediated KO of ADAM17 diminished, whereas plasmid-mediated overexpression of ADAM17 promoted sVLDLR shedding. The amount of shed sVLDLR correlated with an inhibitory effect on the Wnt signaling pathway. Consistent with these in vitro findings, intravitreal injection of an ADAM17 inhibitor reduced sVLDLR levels in the extracellular matrix in the mouse retina. In addition, our results demonstrated that ADAM17 cleaved VLDLR only in cells coexpressing these proteins, suggesting that shedding occurs in a cis manner. Moreover, our study demonstrated that aberrant activation of Wnt signaling was associated with decreased sVLDLR levels, along with down-regulation of ADAM17 in ocular tissues of an age-related macular degeneration model. Taken together, our observations reveal the mechanism underlying VLDLR cleavage and identify a potential therapeutic target for the treatment of disorders associated with dysregulation of Wnt signaling.
C1 [Ma, Xiang; Takahashi, Yusuke; Wu, Wenjing; Liang, Wentao; Chen, Jianglei; Chakraborty, Dibyendu; Li, Yangxiong; Du, Yanhong; Benyajati, Siribhinya; Ma, Jian-Xing] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK 73019 USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center
RP Ma, JX (通讯作者)，Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK 73019 USA.
EM jian-xing-ma@ouhsc.edu
OI Ma, Xiang/0000-0002-2307-1309; Liang, Wentao/0000-0002-0609-6280
FU National Institutes of Health [EY019309, EY012231, EY028949, EY032930,
   EY032931]; Diabetic Animal Core and Histology and Image Core of diabetic
   COBRE [GM122744]; NEI [EY021725]
FX This study was supported by the National Institutes of Health grants
   (EY019309, EY012231, EY028949, EY032930, and EY032931). The content is
   solely the responsibility of the authors and does not necessarily
   represent the official views of the National Institutes of Health. The
   authors like to thank the technical support from the Diabetic Animal
   Core and Histology and Image Core of diabetic COBRE (GM122744) and the
   Vision Core supported by NEI P30 (EY021725). In addition, Dr Qian Chen
   at Xiamen University provided kind assistance and critical discussion in
   this project.
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NR 43
TC 2
Z9 2
U1 2
U2 4
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT
PY 2021
VL 297
IS 4
AR 101185
DI 10.1016/j.jbc.2021.101185
PG 16
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA YZ2PR
UT WOS:000755323700014
PM 34509473
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Ghzaiel, I
   Sassi, K
   Zarrouk, A
   Nury, T
   Ksila, M
   Leoni, V
   Bouhaouala-Zahar, B
   Hammami, S
   Hammami, M
   Mackrill, JJ
   Samadi, M
   Ghrairi, T
   Vejux, A
   Lizard, G
AF Ghzaiel, Imen
   Sassi, Khouloud
   Zarrouk, Amira
   Nury, Thomas
   Ksila, Mohamed
   Leoni, Valerio
   Bouhaouala-Zahar, Balkiss
   Hammami, Sonia
   Hammami, Mohamed
   Mackrill, John J.
   Samadi, Mohammad
   Ghrairi, Taoufik
   Vejux, Anne
   Lizard, Gerard
TI 7-Ketocholesterol: Effects on viral infections and hypothetical
   contribution in COVID-19
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Adjuvant therapies; COVID-19; 7-Ketocholesterol; Oxysterols; SARS-CoV-2;
   Viral diseases
ID CHOLESTEROL OXIDATION; FATTY-ACIDS; POTENTIAL ROLES; OXIDIZED LDL;
   OXYSTEROLS; METABOLISM; CELLS; ATHEROSCLEROSIS; ACCUMULATION;
   INVOLVEMENT
AB 7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins. 7-Ketocholesterol appears to significantly contribute to the development of age-related diseases (cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease), chronic inflammatory bowel diseases and to certain cancers. Recent studies have also shown that 7-ketocholesterol has anti-viral activities, including on SARS-CoV-2, which are, however, lower than those of oxysterols resulting from the oxidation of cholesterol on the side chain. Furthermore, 7-ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. In the case of COVID-19, it can be assumed that the antiviral activity of 7-ketocholesterol could be counterbalanced by its toxic effects, including pro-oxidant, pro-inflammatory and pro-coagulant activities that might promote the induction of cell death in alveolar cells. It is therefore suggested that this oxysterol might be involved in the pathophysiology of COVID-19 by contributing to the acute respiratory distress syndrome and promoting a deleterious, even fatal outcome. Thus, 7-ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome and counteracting its toxic effects with adjuvant therapies might have beneficial effects in COVID-19 patients.
C1 [Ghzaiel, Imen; Sassi, Khouloud; Nury, Thomas; Ksila, Mohamed; Vejux, Anne; Lizard, Gerard] Univ Bourgogne Franche Comt, INSERM, Team Biochem Peroxisome, Inflammat & Lipid Metab EA 7270, F-21000 Dijon, France.
   [Ghzaiel, Imen; Zarrouk, Amira; Hammami, Mohamed] Univ Monastir, Fac Med, LR12ES05, Lab NAFS Nutrit Funct Food & Vasc Hlth, Monastir 5000, Tunisia.
   [Ghzaiel, Imen] Univ Tunis El Manar, Fac Sci Tunis, Tunis 2092, Tunisia.
   [Sassi, Khouloud] Univ Tunis el Manar, Fac Med, Lab Onco Hematol LR05ES05, Tunis 1007, Tunisia.
   [Zarrouk, Amira] Univ Sousse, Fac Med, Sousse, Tunisia.
   [Ghrairi, Taoufik] Univ Tunis El Manar, Fac Sci, Dept Biol, Lobo Neurophysiol Cellular Physiopathol & V, Tunis 2092, Tunisia.
   [Leoni, Valerio] Univ Milano Bicocca, Hosp Desio, ASST Brianza, Clin Chem Lab, I-20900 Monza, Italy.
   [Leoni, Valerio] Univ Milano Bicocca, Hosp Desio, ASST Brianza, Dept Med & Surg, I-20900 Monza, Italy.
   [Bouhaouala-Zahar, Balkiss] Univ Tunis el Manar, Pasteur Inst Tunis, Lab Venoms & Therapeut Mol, Tunis 1002, Tunisia.
   [Mackrill, John J.] Univ Coll Cork, Sch Med, Dept Physiol, Cork, Ireland.
   [Samadi, Mohammad] Univ Lorraine Metz Technopole, ICPM, LCPMC A2, Dept Chem, Metz, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   Universite de Bourgogne; Universite de Monastir; Universite de
   Tunis-El-Manar; Faculte des Sciences de Tunis (FST); Universite de
   Tunis-El-Manar; Faculte de Medecine de Tunis (FMT); Universite de
   Sousse; Universite de Tunis-El-Manar; Faculte des Sciences de Tunis
   (FST); University of Milano-Bicocca; University of Milano-Bicocca; Le
   Reseau International des Instituts Pasteur (RIIP); Universite de
   Tunis-El-Manar; Institut Pasteur Tunis; University College Cork
RP Lizard, G (通讯作者)，Univ Bourgogne Franche Comt, INSERM, Team Biochem Peroxisome, Inflammat & Lipid Metab EA 7270, F-21000 Dijon, France.; Lizard, G (通讯作者)，Univ Bourgogne, INSERM, Fac Sci Gabriel, Laboratoire Bio peroxIL, 6 Bd Gabriel, F-21000 Dijon, France.
EM imenghzaiel93@gmail.com; sassikhouloud@hotmail.com;
   zarroukamira@gmail.com; thomas.nury@u-bourgogne.fr;
   mohamedksila44@gmail.com; valerio.leoni@unimib.it;
   balkiss.bouhaouala@pasteur.rns.tn; sonia.hammami@fmm.rnu.tn;
   mohamed.hammami@fmm.rnu.tn; J.Mackrill@ucc.ie;
   mohammad.samadi@univlorraine.fr; taoufik.ghrairi@fst.utm.tn;
   anne.vejux@u-bourgogne.fr; gerard.lizard@u-bourgogne.fr
RI Leoni, Valerio/AAC-1652-2019
OI SASSI, Khouloud/0000-0003-3372-0242; LEONI, VALERIO/0000-0002-8954-0366
FU University Tunis El Manar; Association Bourguignonne pour les
   Applications des Sciences de l'Information en Medecine
FX The authors acknowledge the European Network for Oxysterols Research
   (ENOR: http://oxysterols.net) which permits discussion and collaborative
   research between the members. Khouloud Sassi (MS; Ph.D student) , Amira
   Zarrouk (Ph.D) , Thomas Nury (Ph.D) , Valerio Leoni (M. D, Ph.D) , John
   J. Mackrill (Ph.D) , Mohammad Samadi (Ph.D) , Anne Vejux (Ph.D) and
   Gerard Lizard (Ph.D, D.Sc) are all members of ENOR. The authors
   acknowledge the University Tunis El Manar for the financial support of
   Mrs Imen Ghzaiel (M.S, Ph.D student) , Mrs Khouloud Sassi (M.S, Ph.D
   student) and Mr Mohamed Ksila (M.S, Ph.D student) as well as the
   "Association Bourguignonne pour les Applications des Sciences de
   l'Information en Medecine" (A.B.A.S.I.M) .
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NR 111
TC 11
Z9 11
U1 1
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
EI 1879-1220
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD SEP
PY 2021
VL 212
AR 105939
DI 10.1016/j.jsbmb.2021.105939
EA JUN 2021
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA UF2LN
UT WOS:000688410500014
PM 34118414
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Bourdon, L
   Jensen, AA
   Kavanagh, JM
   McClure, DD
AF Bourdon, Loic
   Jensen, Andreas A.
   Kavanagh, John M.
   McClure, Dale D.
TI Microalgal production of zeaxanthin
SO ALGAL RESEARCH-BIOMASS BIOFUELS AND BIOPRODUCTS
LA English
DT Article
DE Zeaxanthin; Microalgae; Photo-bioreactor; Synechococcus; Cyanobacteria;
   Rhodophyte
ID BIOTECHNOLOGICAL PRODUCTION; CULTURE-CONDITIONS; BIOFILM FORMATION;
   BETA-CAROTENE; LUTEIN; CYANOBACTERIUM; LIGHT; BIOSYNTHESIS;
   ACCUMULATION; TEMPERATURE
AB Zeaxanthin is a carotenoid pigment used in the food industry as well as in supplements for age-related macular degeneration. There is potential for microalgae to be used for zeaxanthin production, however there is relatively little work examining this issue, particularly with respect to scale-up. Here two species of cyanobacteria (Synechococcus sp. PCC7002 and Synechocystis sp. PCC6803) were examined, along with a Rhodophyte (Rhodosorus sp.). At a light intensity of 80 ?mol photons m- 2 s- 1 specific zeaxanthin contents were 2.30 ? 0.84, 1.61 ? 0.68 and 2.16 ? 0.63 mg g-1 for Synechococcus sp. PCC7002, Synechocystis sp. PCC6803 and Rhodosorus sp., respectively. Of the species examined the Synechococcus PCC7002 had the highest specific growth rate (0.74 ? 0.09 day-1). This species was used to further optimize the process, increasing the nutrient concentration in the medium and using an incremental light addition strategy led to an approximately 13-fold increase in the cell density, giving a final dry cell weight of 4.25 ? 1.42 g L-1. Results from this work are among the highest in the literature for zeaxanthin productivity (0.7 ? 0.5 mg L-1 day- 1) and the approach used can be readily scaled-up. Additionally, the approach used in this work to achieve high cell densities of PCC7002 could be potentially applied to the production of other compounds (e.g. phycobilins or compounds produced using metabolic engineering).
C1 [Bourdon, Loic; Jensen, Andreas A.; Kavanagh, John M.; McClure, Dale D.] Univ Sydney, Sch Chem & Biomol Engn, Bldg J01, Sydney, NSW 2006, Australia.
C3 University of Sydney
RP McClure, DD (通讯作者)，Univ Sydney, Sch Chem & Biomol Engn, Bldg J01, Sydney, NSW 2006, Australia.
EM dale.mcclure@sydney.edu.au
OI Bourdon, Loic/0000-0003-0213-5614; McClure, Dale/0000-0001-6790-5179
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NR 43
TC 6
Z9 6
U1 4
U2 13
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 2211-9264
J9 ALGAL RES
JI Algal Res.
PD MAY
PY 2021
VL 55
AR 102266
DI 10.1016/j.algal.2021.102266
EA MAR 2021
PG 8
WC Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology
GA RQ5JU
UT WOS:000642455500007
DA 2022-11-30
ER

PT J
AU Parolini, B
   Di Salvatore, A
   Pinackatt, SJ
   Baldi, A
   Besozzi, G
   Finzi, A
   Cardillo, D
   Sallam, AB
   Frisina, R
AF Parolini, Barbara
   Di Salvatore, Attilio
   Pinackatt, Sajish Joseph
   Baldi, Andrea
   Besozzi, Gianluca
   Finzi, Alessandro
   Cardillo, Daniele
   Sallam, Ahmed B.
   Frisina, Rino
TI LONG-TERM RESULTS OF AUTOLOGOUS RETINAL PIGMENT EPITHELIUM AND CHOROID
   TRANSPLANTATION FOR THE TREATMENT OF EXUDATIVE AND ATROPHIC
   MACULOPATHIES
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE AMD; atrophic maculopathy; choroid; choroidal neovascular membrane;
   exudative maculopathy; retinal pigment epithelium; macula; macular
   degeneration; patch; RPE-choroid transplantation
ID MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; TRANSLOCATION; RANIBIZUMAB;
   AFLIBERCEPT; SURGERY; THERAPY; GRAFT; SHEET; RPE
AB Purpose: To evaluate the long-term results of autologous retinal pigment epithelium (RPE) and choroid transplantation (RPE-choroid patch) for exudative and atrophic maculopathies. Methods: Consecutive chart review of 120 eyes, which underwent RPE-choroid patch, from 2007 to 2017 for RPE atrophy or choroidal neovascular membrane secondary to exudative and hemorrhagic age-related macular degeneration, myopia, angioid streaks, and laser. Eyes were tested with best-corrected visual acuity (BCVA), reading ability, optical coherence tomography, fluorescein angiography and indocyanine green angiography, autofluorescence, and microperimetry. Results: Eighty-eight eyes of 84 patients had complete data, with 2- to 10-year follow-up. Mean age was 71.9 +/- 9.06 years. Mean preoperative and postoperative BCVA was 20/320 (1.2 +/- 0.2 logMAR) and 20/200 (0.94 +/- 0.36 logMAR), respectively (P = 0.009). Reading ability recovered in 43% of cases. Microperimetry showed central fixation. A gain of at least 15 letters was obtained in 40% of eyes. Integrity (P = 0.009) of external limiting membrane and higher preoperative BCVA (P = 0.001) predicted better final BCVA. Complications were retinal detachment (11.4%), macular atrophy (7%), subretinal hemorrhage (4.5%), epiretinal membrane (4.5%), recurrent choroidal neovascular membrane (4.5%), macular hole (3.4%), and cystoid edema (3%). Conclusion: Autologous RPE-choroid patch achieved long-lasting BCVA improvement and central fixation, in eyes with choroidal neovascular membrane and intact external limiting membrane. Atrophic maculopathies only obtained temporary visual benefit.
C1 [Di Salvatore, Attilio; Pinackatt, Sajish Joseph; Baldi, Andrea; Besozzi, Gianluca; Finzi, Alessandro; Cardillo, Daniele] S Anna Clin Inst, Dept Ophthalmol, Brescia, Italy.
   [Sallam, Ahmed B.] Univ Arkansas Med Sci, Jones Eye Inst, Dept Ophthalmol, Little Rock, AR 72205 USA.
   [Frisina, Rino] Univ Padua, Dept Ophthalmol, Padua, Italy.
   [Parolini, Barbara] Eyecare Clin, Dept Ophthalmol, Brescia, Italy.
C3 University of Arkansas System; University of Arkansas Medical Sciences;
   University of Padua
RP Parolini, B (通讯作者)，S Anna Clin Inst, Via Franzone 31, I-25127 Brescia, Italy.
EM parolinibarbara@gmail.com
RI Frisina, Rino/C-4477-2019; Sallam, Ahmed/A-4791-2014
OI Frisina, Rino/0000-0002-0247-2680; Sallam, Ahmed/0000-0001-7207-6782
CR Brown DM, 2009, OPHTHALMOLOGY, V116, P57, DOI 10.1016/j.ophtha.2008.10.018
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NR 27
TC 7
Z9 9
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 MAR
PY 2020
VL 40
IS 3
BP 507
EP 520
DI 10.1097/IAE.0000000000002429
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LA1RI
UT WOS:000523731700014
PM 30608346
DA 2022-11-30
ER

PT J
AU Rabiolo, A
   Benatti, L
   Tomasso, L
   Zucchiatti, I
   Gelormini, F
   Casaluci, M
   Querques, L
   Sacconi, R
   Bandello, F
   Querques, G
AF Rabiolo, Alessandro
   Benatti, Lucia
   Tomasso, Livia
   Zucchiatti, Ilaria
   Gelormini, Francesco
   Casaluci, Marco
   Querques, Lea
   Sacconi, Riccardo
   Bandello, Francesco
   Querques, Giuseppe
TI RETINAL ARTERIAL DILATION IS IMPAIRED IN EYES WITH DRUSEN AND RETICULAR
   PSEUDODRUSEN
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; arteriovenous ratio; drusen; dynamic
   vessel analyzer; reticular pseudodrusen; static vessel analysis
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; VASCULAR CALIBER;
   OPTIC-NERVE; FLICKER; ATHEROSCLEROSIS; ASSOCIATION; INFLAMMATION;
   PROGRESSION; MECHANISMS
AB Purpose: To analyze static characteristics and dynamic functionality of retinal vessels in eyes with drusen and reticular pseudodrusen (RPD) using dynamic vessel analyzer.
   Methods: Patients with clinical diagnosis of isolated RPD or medium-large drusen and healthy controls were enrolled in the study between July 2016 and May 2018. Participants underwent complete ophthalmologic examination, including enhanced depth imaging structural optical coherence tomography, dynamic retinal vessel analysis, and static retinal vessel analysis.
   Results: Twenty-eight eyes of 23 patients with drusen (9 men, mean age 77 +/- 6 years), 22 eyes of 16 patients with RPD (7 men, mean age: 76 +/- 6 years), and 22 eyes of 22 control subjects (11 men, mean age of 75 +/- 6 years) were enrolled. Static retinal vessel analysis did not show any significant difference between the three groups for the central retinal artery equivalent (P = 0.11), the central retinal vein equivalent (P = 0.27), and the arteriovenous ratio (P = 0.30). Dynamic vessel analysis showed significantly reduced arterial dilation in eyes with drusen (P = 0.0001) and RPD (P = 0.015) compared with control subjects. No significant difference was seen between drusen and RPD groups (P = 0.32). Dynamic vessel analysis of retinal veins showed no differences between the three groups (P = 0.10).
   Conclusion: Dynamic vessel analysis in eyes with drusen and RPD revealed an impaired retinal arterial dilation in response to flicker light stimulation, which further supports the relationship between cardiovascular risk and age-related macular degeneration.
C1 [Rabiolo, Alessandro; Benatti, Lucia; Tomasso, Livia; Zucchiatti, Ilaria; Gelormini, Francesco; Casaluci, Marco; Querques, Lea; Sacconi, Riccardo; Bandello, Francesco; Querques, Giuseppe] Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Dept Ophthalmol, Via Olgettina 60, I-20132 Milan, Italy.
   [Sacconi, Riccardo] Univ Verona, Eye Clin, Dept Neurol & Movement Sci, Verona, Italy.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele;
   University of Verona
RP Querques, G (通讯作者)，Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Dept Ophthalmol, Via Olgettina 60, I-20132 Milan, Italy.
EM giuseppe.querques@hotmail.it
RI Benatti, Lucia/AAZ-3035-2020; Rabiolo, Alessandro/J-2831-2019;
   Zucchiatti, Ilaria/ABA-7083-2020
OI bandello, francesco/0000-0003-3238-9682; Sacconi,
   Riccardo/0000-0003-2891-2012; Querques, Giuseppe/0000-0002-3292-9581;
   Rabiolo, Alessandro/0000-0002-7772-5929
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NR 46
TC 4
Z9 4
U1 1
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 NOV
PY 2019
VL 39
IS 11
BP 2205
EP 2211
DI 10.1097/IAE.0000000000002283
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KC9FQ
UT WOS:000507477300023
PM 30074940
DA 2022-11-30
ER

PT J
AU Wu, D
   Kanda, A
   Liu, Y
   Kase, S
   Noda, K
   Ishida, S
AF Wu, Di
   Kanda, Atsuhiro
   Liu, Ye
   Kase, Satoru
   Noda, Kousuke
   Ishida, Susumu
TI Galectin-1 promotes choroidal neovascularization and subretinal fibrosis
   mediated via epithelial-mesenchymal transition
SO FASEB JOURNAL
LA English
DT Article
DE AMD; RPE; SMAD family member 2; TGF-; VEGF
ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-KAPPA-B; MACULAR DEGENERATION;
   EXPRESSION; HYPOXIA; CANCER; ICAM-1; CELLS; NONRESPONDERS; INFLAMMATION
AB VEGFA and TGF- are known major angiogenic and fibrogenic factors. Galectin-1, encoded by lectin, galactoside-binding, soluble (LGALS)1, has attracted growing attention for its facilitatory role in angiogenesis and fibrosis through its modification of VEGFA and TGF- receptor signaling pathways. We reveal galectin-1 involvement in the mouse model of laser-induced choroidal neovascularization (CNV) and subretinal fibrosis, both of which represent the pathogenesis of age-related macular degeneration (AMD). Neither deletion nor overexpression of Lgals1 affected physiologic retinal development or visual function. Galectin-1/Lgals1 was upregulated by CNV induction, whereas deletion of Lgals1 suppressed CNV together with downstream molecules of VEGF receptor (VEGFR)2. Loss of Lgals1 also attenuated subretinal fibrosis, expression of epithelial-mesenchymal transition (EMT) markers including Snai1, and phosphorylation of SMAD family member 2. Supporting these in vivo findings, silencing of LGALS1 in human retinal pigment epithelial (RPE) cells inhibited TGF-1-induced EMT-related molecules and cell motilities. Conversely, overexpression of Lgals1 enhanced CNV and subretinal fibrosis. Specimens from patients with AMD demonstrated colocalization of galectin-1 with VEGFR2 in neovascular endothelial cells and with phosphorylated SMAD2 in RPE cells. These results suggested a biologic significance of galectin-1 as a key promotor for both angiogenesis and fibrosis in eyes with AMD.Wu, D., Kanda, A., Liu, Y., Kase, S., Noda, K., Ishida, S. Galectin-1 promotes choroidal neovascularization and subretinal fibrosis mediated via epithelial-mesenchymal transition.
C1 Hokkaido Univ, Lab Ocular Cell Biol & Visual Sci, Dept Ophthalmol, Fac Med, Sapporo, Hokkaido, Japan.
   Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan.
C3 Hokkaido University; Hokkaido University
RP Kanda, A (通讯作者)，Hokkaido Univ, Lab Ocular Cell Biol & Visual Sci, Dept Ophthalmol, Fac Med,Kita Ku, N-15 W-7, Sapporo, Hokkaido 0608638, Japan.; Kanda, A (通讯作者)，Hokkaido Univ, Grad Sch Med, Kita Ku, N-15 W-7, Sapporo, Hokkaido 0608638, Japan.
EM kanda@med.hokudai.ac.jp
FU Bayer Yakuhin Ltd.; Uehara Memorial Foundation; Eye Research Foundation
   for the Aged; Japan National Society for the Prevention of Blindness;
   Otsuka Toshimi Scholarship Foundation; China Scholarship Council
FX The authors thank Ikuyo Hirose, Shiho Yoshida, and Miyuki Murata
   (Hokkaido University) for skilled technical assistance. This work was
   supported, in part, by Bayer Yakuhin Ltd., the Uehara Memorial
   Foundation, the Eye Research Foundation for the Aged, and the Japan
   National Society for the Prevention of Blindness (to A.K.). D.W. and
   Y.L. are recipients of scholarships from the Otsuka Toshimi Scholarship
   Foundation and China Scholarship Council, respectively. The authors
   declare no conflicts of interest.
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NR 54
TC 34
Z9 35
U1 0
U2 11
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 FEB
PY 2019
VL 33
IS 2
BP 2498
EP 2513
DI 10.1096/fj.201801227R
PG 16
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 HJ6KJ
UT WOS:000457296600077
PM 30277820
DA 2022-11-30
ER

PT J
AU Arunkumar, R
   Calvo, CM
   Conrady, CD
   Bernstein, PS
AF Arunkumar, Ranganathan
   Calvo, Charles M.
   Conrady, Christopher D.
   Bernstein, Paul S.
TI What do we know about the macular pigment in AMD: the past, the present,
   and the future
SO EYE
LA English
DT Review
ID HETEROCHROMATIC FLICKER PHOTOMETRY; MESO-ZEAXANTHIN; BETA-CAROTENE;
   OPTICAL-DENSITY; EYE DISEASE; INTESTINAL-ABSORPTION; RETINAL
   ACCUMULATION; CONTRAST SENSITIVITY; DIETARY CAROTENOIDS;
   EPITHELIAL-CELLS
AB Carotenoids are lipophilic isoprenoid pigments with a common C40H56 core chemical structure that are naturally synthesized by many plants, algae, bacteria, and fungi. Humans and animals cannot synthesize carotenoids de novo and must obtain them solely through dietary sources. Among the more than 750 carotenoids in nature, only lutein, zeaxanthin, meso-zeaxanthin, and their oxidative metabolites selectively accumulate in the foveal region of the retina where they are collectively referred to as the macular pigment (MP) of the macula lutea. MP serves an ocular protective role through its ability to filter phototoxic blue light radiation and also via its antioxidant activity. These properties have led to the hypothesis that carotenoids may protect against the development of age-related macular degeneration (AMD), the most common cause of blindness in the aged population >60 years old. Epidemiological studies have supported this by showing that patients with lower concentrations of serum carotenoids and macular pigment optical density (MPOD) measurements are at a higher risk of developing AMD. Conversely, nutritional supplementation and diets rich in lutein and zeaxanthin readily impact MP concentrations and reduce the risk of progression to advanced AMD, and the AREDS2 supplement formulation containing 10 mg of lutein and 2 mg of zeaxanthin is the standard-of-care recommendation for individuals at risk for visual loss from advanced AMD. This article reviews the rich history of research on the MP dating back to the 1700s and outlines their potential for further therapeutic improvements for AMD in the future.
C1 [Arunkumar, Ranganathan; Calvo, Charles M.; Conrady, Christopher D.; Bernstein, Paul S.] Univ Utah, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT 84112 USA.
C3 Utah System of Higher Education; University of Utah
RP Bernstein, PS (通讯作者)，Univ Utah, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT 84112 USA.
EM paul.bernstein@hsc.utah.edu
OI Bernstein, Paul/0000-0002-4228-7666
FU NIH [EY11600, EY14800]; Research to Prevent Blindness; NATIONAL EYE
   INSTITUTE [R01EY011600, R29EY011600, P30EY014800] Funding Source: NIH
   RePORTER
FX This work was supported in part by NIH grants EY11600 and EY14800 and by
   an unrestricted departmental grant from Research to Prevent Blindness.
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NR 98
TC 43
Z9 44
U1 2
U2 31
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 MAY
PY 2018
VL 32
IS 5
BP 992
EP 1004
DI 10.1038/s41433-018-0044-0
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GF3FR
UT WOS:000431831500016
PM 29576617
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Santoro, D
   Siligato, R
   Vadala, C
   Lucanto, M
   Cristadoro, S
   Conti, G
   Buemi, M
   Costa, S
   Sabadini, E
   Magazzu, G
AF Santoro, Domenico
   Siligato, Rossella
   Vadala, Carmela
   Lucanto, Mariacristina
   Cristadoro, Simona
   Conti, Giovanni
   Buemi, Michele
   Costa, Stefano
   Sabadini, Ettore
   Magazzu, Giuseppe
TI C3 glomerulopathy in cystic fibrosis: a case report
SO BMC NEPHROLOGY
LA English
DT Article
DE C3 glomerulopathy; Renal biopsy; Cystic fibrosis; Inflammation
ID DENSE DEPOSIT DISEASE; COMPLEMENT ABNORMALITIES; GLOMERULONEPHRITIS;
   ECULIZUMAB; MUTATION
AB Background: C3 glomerulonephritis is a rare glomerulopathy characterized at renal biopsy by C3 deposition, alone or with scanty immunoglobulins, as well as by an electron-dense material in mesangium, subendothelial and subepithelial space. An abnormal systemic activation of the alternative pathway of the complement cascade is responsible for the development of the disease if triggered by several possible environmental conditions. We report the first case in literature of a patient affected by cystic fibrosis and C3GN.
   Case presentation: Our case involves a young woman with cystic fibrosis, who had persistent microscopic hematuria, proteinuria and hypocomplementemia C3 for over three months. Renal biopsy confirmed the diagnosis of C3 glomerulopathy. Complement system dysregulation was tested and resulted in a strong terminal pathway activation proved by high levels of sC5b-9 complex, amounting to 1588 ng/ml (normal value < 400 ng/ml). Next generation sequencing (NGS) showed polymorphism in CFH (p.V62I in SCR1) and THBD (p.A473V), already known as pathogenic for C3GN, as well as a mutation in C3 (p.R102G) associated only with age-related macular degeneration (AMD) so far. Treatment was based on ACE inhibitors and kidney function is currently stable (GFR 50 ml/min, serum creatinine 1.7).
   Conclusions: The co-existence of C3 glomerulopathy in a patient with CF, which is characterized by chronic infection/inflammation, makes this case an interesting model of chronic altered systemic activation of the alternative pathway of the complement cascade.
C1 [Santoro, Domenico; Siligato, Rossella; Vadala, Carmela; Buemi, Michele] Univ Messina, Dept Clin & Expt Med, Via Faranda 2, I-98123 Messina, Italy.
   [Lucanto, Mariacristina; Cristadoro, Simona; Costa, Stefano; Magazzu, Giuseppe] Univ Messina, Unit Pediat Gastroenterol & Cyst Fibrosis, Messina, Italy.
   [Conti, Giovanni] Univ Messina, Unit Pediat Nephrol & Rheumatol, Messina, Italy.
   [Sabadini, Ettore] Hosp Riuniti, Unit Nephrol, Bergamo, Italy.
C3 University of Messina; University of Messina; University of Messina;
   Ospedali Riuniti di Bergamo
RP Santoro, D (通讯作者)，Univ Messina, Dept Clin & Expt Med, Via Faranda 2, I-98123 Messina, Italy.
EM dsantoro@unime.it
RI santoro, domenico/P-7902-2014; Conti, Giovanni/AAF-1059-2020; Siligato,
   Rossella/AAC-7078-2022
OI santoro, domenico/0000-0002-4279-6559; Siligato,
   Rossella/0000-0001-7320-7019; Costa, Stefano/0000-0001-5640-1901
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NR 19
TC 0
Z9 0
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2369
J9 BMC NEPHROL
JI BMC Nephrol.
PD MAR 28
PY 2018
VL 19
AR 73
DI 10.1186/s12882-018-0880-y
PG 5
WC Urology & Nephrology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Urology & Nephrology
GA GA9LO
UT WOS:000428663000001
PM 29592796
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hirata, J
   Ko, JA
   Mochizuki, H
   Funaishi, K
   Yamane, K
   Sonoda, KH
   Kiuchi, Y
AF Hirata, Junko
   Ko, Ji-Ae
   Mochizuki, Hideki
   Funaishi, Kunihiko
   Yamane, Ken
   Sonoda, Koh-Hei
   Kiuchi, Yoshiaki
TI Oxidative stress regulates expression of claudin-1 in human RPE cells
SO CENTRAL EUROPEAN JOURNAL OF BIOLOGY
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium; Oxidative
   stress; Claudin-1; Tight junction; p38; Mitogen-activated protein kinase
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; ARPE-19 CELLS;
   GROWTH-FACTOR; UP-REGULATION; PROTEINS; INDUCTION; BARRIER; DAMAGE
AB Age-related macular degeneration (AMD) is a neurodegenerative disease associated with irreversible loss of central vision in the elderly. Disruption of the homeostatic function of the retinal pigment epithelium (RPE) is thought to be fundamental to AMD pathogenesis, and oxidative stress is implicated in the associated RPE damage. We examined the effects of oxidative stress on the expression of junctional proteins in cultured human retinal pigment epithelial (ARPE-19) cells. Reverse transcription-PCR and immunoblot analyses revealed that expression of the tight-junction protein claudin-1 was increased at both the mRNA and protein levels 8 to 12 h after exposure of ARPE-19 cells to H2O2, whereas that of the tight-junction protein ZO-1 or the adherens-junction protein N-cadherin was unaffected. Expression of both claudin-1 and N-cadherin was down-regulated by exposure of the cells to H2O2 for longer periods (24 to 48 h). Oxidative stress also induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) with a time course similar to that apparent for the up-regulation of claudin-1 expression. Furthermore, the increase in the abundance of claudin-1 induced by H2O2 was blocked by the p38 inhibitor SB203580. Phosphorylation of the MAPKs ERK and JNK was not affected by H2O2. Our results suggest that modulation of claudin-1 expression in the RPE by oxidative stress may contribute to the pathogenesis of AMD.
C1 [Hirata, Junko; Ko, Ji-Ae; Mochizuki, Hideki; Funaishi, Kunihiko; Yamane, Ken; Kiuchi, Yoshiaki] Hiroshima Univ, Grad Sch Biomed Sci, Dept Ophthalmol, Hiroshima 7348551, Japan.
   [Sonoda, Koh-Hei] Yamaguchi Univ, Grad Sch Med, Dept Ophthalmol, Ube, Yamaguchi 7558505, Japan.
C3 Hiroshima University; Yamaguchi University
RP Hirata, J (通讯作者)，Hiroshima Univ, Grad Sch Biomed Sci, Dept Ophthalmol, 1-2-3 Minami Kasumi, Hiroshima 7348551, Japan.
EM jiaeko@hiroshima-u.ac.jp
FU Japan Society for the Promotion of Science (KAKENHI) [23592571]
FX This work was supported by a grant (no. 23592571) from the Japan Society
   for the Promotion of Science (KAKENHI).
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NR 26
TC 4
Z9 4
U1 1
U2 21
PU DE GRUYTER POLAND SP ZOO
PI WARSAW
PA BOGUMILA ZUGA 32A STR., 01-811 WARSAW, POLAND
SN 1895-104X
EI 1644-3632
J9 CENT EUR J BIOL
JI Cent. Eur. J. Biol.
PD MAY
PY 2014
VL 9
IS 5
BP 461
EP 468
DI 10.2478/s11535-014-0287-0
PG 8
WC Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics
GA AB2TB
UT WOS:000331643900001
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Agrawal, R
   Iyer, J
   Connolly, J
   Iwata, D
   Teoh, S
AF Agrawal, Rupesh
   Iyer, Jayant
   Connolly, John
   Iwata, Daiju
   Teoh, Stephen
TI Cytokines and Biologics in non-infectious autoimmune uveitis: Bench to
   Bedside
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Aqueous humor; biologics; biological signatures; cytokines; intraocular
   inflammation; multiplex bead assays
ID JUVENILE IDIOPATHIC ARTHRITIS; AQUEOUS-HUMOR; ETANERCEPT; INFLIXIMAB;
   DISEASE; EFFICACY; THERAPY; MECHANISMS; PROFILES; CHILDREN
AB Intraocular inflammatory eye disease is one of the important causes of ocular morbidity. Even though the prevalence of uveitis is less common in relation to diabetic retinopathy, glaucoma or age related macular degeneration, the complexity and heterogeneity of the disease makes it more unique. Putative uveitogenic retinal antigens incite innate immunity by the process of antigen mimicry and have been shown to be associated in patients with intraocular inflammatory disease by numerous experimental studies. Laboratory diagnostic tools to aid the etiologic association in intraocular inflammatory disease have evolved over the last two decades and we are entering into an era of molecular diagnostic tests. Sophisticated novel technologies such as multiplex bead assays to assess biological signatures have revolutionized the management of complex refractory uveitis. Nevertheless, there is still a long way to go to establish the causal relationship between these biomarkers and specific uveitic entities. Experimental studies have shown the supreme role of infliximab in the management of Behcet's disease. Despite significant experimental and case control studies, the deficiency of randomized clinical trials using these biologic agents has handicapped us in exploring them as a front line therapy in severe refractory uveitis. Studies still need to answer the safety of these potentially life threatening drugs in a selected group of patients and determine when to commence and for how long the treatment has to be given. This review article covers some basic concepts of cytokines in uveitis and their potential application for therapy in refractory uveitis.
C1 [Agrawal, Rupesh; Teoh, Stephen] Tan Tock Seng Hosp, Natl Healthcare Grp, Inst Eye, Singapore 308433, Singapore.
   [Iyer, Jayant] Singapore Natl Eye Ctr, Singapore, Singapore.
   [Connolly, John] ASTAR, Singapore Immunol Network, Singapore, Singapore.
   [Agrawal, Rupesh; Iwata, Daiju] UCL, Translat Vis Res Lab, London, England.
C3 Tan Tock Seng Hospital; Singapore National Eye Center; Agency for
   Science Technology & Research (A*STAR); A*STAR - Singapore Immunology
   Network (SIgN); University of London; University College London
RP Agrawal, R (通讯作者)，Tan Tock Seng Hosp, Natl Healthcare Grp, Inst Eye, Dept Ophthalmol, Singapore 308433, Singapore.
EM rupesh_agrawal@ttsh.com.sg
OI Teoh, Stephen/0000-0002-9359-9694
FU National Medical Research Council (Singapore) Overseas research training
   fellowship at University College London & Moorfields Eye Hospital
FX Dr Rupesh Agrawal is funded by National Medical Research Council
   (Singapore) Overseas research training fellowship at University College
   London & Moorfields Eye Hospital.
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NR 40
TC 22
Z9 25
U1 0
U2 3
PU WOLTERS KLUWER MEDKNOW PUBLICATIONS
PI MUMBAI
PA WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S  NO 1498A-2
   VILLAGE MAROL, ANDHERI EAST, MUMBAI, 400059, INDIA
SN 0301-4738
EI 1998-3689
J9 INDIAN J OPHTHALMOL
JI Indian J. Ophthalmol.
PD JAN
PY 2014
VL 62
IS 1
BP 74
EP 81
DI 10.4103/0301-4738.126187
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AA4RP
UT WOS:000331084100012
PM 24492505
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Rifkin, L
   Schaal, S
AF Rifkin, Lana
   Schaal, Shlomit
TI Shortening ocular pain duration following intravitreal injections
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Artificial tears; Intravitreal
   injection; Nonsteroidal anti-inflammatory drugs; Ocular pain
AB PURPOSE. To determine ocular pain duration after routine in-office intravitreal injection and to determine whether topical eyedrops are beneficial in increasing patient comfort.
   METHODS. Forty injection-naive patients receiving routine intravitreal injections of bevacizumab for age-related macular degeneration were randomized into 3 groups: group 1 (control, no drops), group 2 (generic artificial tears), and group 3 (ketorolac tromethamine 0.4% eyedrops). Those who received topical medications were given a Visual Analog Pain score survey and asked to record their pain on a scale from 0 (no distress) to 10 (unbearable distress) daily until a score of 0 was achieved, at which point they were instructed to discontinue use of their given drops. Self-reported pain scores were assessed.
   RESULTS. Pain after routine intravitreal injection lasts on average between 3 and 7 days. Patients receiving topical ketorolac eyedrops reported the fewest average number of pain days (2.25 +/- 1.22) vs patients receiving artificial tears (3.54 +/- 1.13) or those who received no postprocedure eyedrops (5.13 +/- 1.25); p<0.05. At most, patients receiving ketorolac eyedrops reported 3 days of recordable pain. Those who received artificial tears reported at most 5 days of recordable pain, and patients who did not receive any postprocedure eyedrops reported at most 7 days of recordable pain.
   CONCLUSIONS. Pain after intravitreal injection is generally mild, may be reduced by postinjection topical ketorolac eyedrops, and lasts less than 1 week.
C1 [Rifkin, Lana; Schaal, Shlomit] Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA.
C3 University of Louisville
RP Schaal, S (通讯作者)，301E Muhammad Ali Blvd, Louisville, KY 40202 USA.
EM s.schaal@louisville.edu
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NR 19
TC 14
Z9 14
U1 0
U2 0
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 NOV-DEC
PY 2012
VL 22
IS 6
BP 1008
EP 1012
DI 10.5301/ejo.5000147
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 050HF
UT WOS:000312043200020
PM 22562296
DA 2022-11-30
ER

PT J
AU Kramann, CA
   Schopfer, K
   Lorenz, K
   Zwiener, I
   Stoffelns, BM
   Pfeiffer, N
AF Kramann, Christina A.
   Schoepfer, Kilian
   Lorenz, Katrin
   Zwiener, Isabella
   Stoffelns, Bernhard M.
   Pfeiffer, Norbert
TI Intravitreal ranibizumab treatment of retinal angiomatous proliferation
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; intravitreal injection; Lucentis;
   ranibizumab; retinal angiomatous proliferation
ID BEVACIZUMAB AVASTIN TREATMENT; PHOTODYNAMIC THERAPY; MACULAR
   DEGENERATION; SURGICAL ABLATION; CHOROIDAL NEOVASCULARIZATION;
   TRIAMCINOLONE ACETONIDE; VERTEPORFIN; ANASTOMOSIS; RISK
AB Purpose: To determine the efficacy of intravitreal injections of ranibizumab in the treatment of retinal angiomatous proliferation (RAP) in neovascular age-related macular degeneration. Methods: Retrospective, consecutive case series of 26 eyes (26 patients) treated with intravitreal injections of 0.5 mg ranibizumab for RAP. Patients received intravitreal injections at monthly intervals during upload phase for a 3-month period. Results: Mean visual acuity before treatment was 0.75 +/- 0.38logMAR (mean +/- SD, n = 26). In the upload phase, mean visual acuity improved 4 weeks after the initial injection to 0.6 +/- 0.37logMAR (n = 26) and to 0.53 +/- 0.34logMAR (n = 26) 4 weeks after the third monthly intravitreal injection of ranibizumab. The mean optical coherence tomography (OCT) central foveal thickness reduced from 345 +/- 55 mu m at baseline to 215 +/- 87 mu m at 3 months. In the maintenance phase, mean visual acuity after 6 months was 0.66 +/- 0.38logMAR (n = 12) and 0.7 +/- 0.37logMAR after 9 months (n = 6). The mean OCT central foveal thickness was 259 +/- 59 mu m (n = 13) at 6 months and 280 +/- 127 mu m (n = 6) at nine-month follow-up. Conclusion: Intravitreal ranibizumab resulted in an improvement of visual acuity 4 weeks after the first injection but was more pronounced after 3 months. A reduction in leakage and OCT central foveal thickness was seen 3 months after the commencement of treatment.
C1 [Kramann, Christina A.; Schoepfer, Kilian; Lorenz, Katrin; Stoffelns, Bernhard M.; Pfeiffer, Norbert] Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, Dept Ophthalmol, D-55131 Mainz, Germany.
   [Zwiener, Isabella] Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, IMBEI, D-55131 Mainz, Germany.
C3 Johannes Gutenberg University of Mainz; Johannes Gutenberg University of
   Mainz
RP Kramann, CA (通讯作者)，Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, Dept Ophthalmol, Langenbeckstr 1, D-55131 Mainz, Germany.
EM kramann@augen.klinik.uni-mainz.de
RI Pfeiffer, Norbert/AAO-7586-2020
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NR 31
TC 15
Z9 17
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 AUG
PY 2012
VL 90
IS 5
BP 487
EP 491
DI 10.1111/j.1755-3768.2010.01952.x
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 980OV
UT WOS:000306903600041
PM 20584002
OA Bronze
DA 2022-11-30
ER

PT J
AU Lima, LH
   Laud, K
   Freund, KB
   Yannuzzi, LA
   Spaide, RF
AF Lima, Luiz H.
   Laud, Ketan
   Freund, K. Bailey
   Yannuzzi, Lawrence A.
   Spaide, Richard F.
TI ACQUIRED VITELLIFORM LESION ASSOCIATED WITH LARGE DRUSEN
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE acquired vitelliform lesion; age-related macular degeneration; cuticular
   drusen; fundus autofluorescence; large drusen; spectral domain optical
   coherence tomography
ID MACULAR DEGENERATION; DEPOSITS; DETACHMENT; HYPOTHESIS; DYSTROPHY;
   RETINA; CELLS
AB Purpose: The purpose of this study was to describe the association of acquired vitelliform lesion (AVL) and large drusen in patients with non-neovascular age-related macular degeneration.
   Methods: A retrospective review of clinical examination and multimodal imaging data of patients with AVL and large drusen seen over a 12-month period was performed. Acquired vitelliform lesion was defined as subretinal accretion of hyperautofluorescent yellowish material within the macular region not due to vitelliform macular dystrophy. Large drusen were diagnosed by the presence of mounded deposits in the subretinal pigment epithelial space between the retinal pigment epithelium and the Bruch membrane using multimodal imaging analysis (color photography, autofluorescence, and spectral domain optical coherence tomography).
   Results: Thirteen eyes of 9 white patients with a mean age of 74 years were observed to have AVL associated with large drusen. The median visual acuity was 20/60. All AVLs were hyperautofluorescent and were located in the subretinal space between the retinal pigment epithelium and the photoreceptor inner segment/outer segment junction. The AVL in this series had similar color, autofluorescence, and optical coherence tomographic findings as the AVL seen in association with cuticular drusen and subretinal drusenoid deposits.
   Conclusion: Acquired vitelliform lesions, which have previously been related to cuticular drusen and subretinal drusenoid deposits, can occur in association with large drusen. Abnormalities leading to drusen formation or processes that function in parallel to these may be causative in AVL formation. RETINA 32:647-651, 2012
C1 [Lima, Luiz H.; Laud, Ketan; Freund, K. Bailey; Yannuzzi, Lawrence A.; Spaide, Richard F.] Macula Consultants New York, Vitreous, Retina, New York, NY USA.
   [Lima, Luiz H.; Laud, Ketan; Freund, K. Bailey; Yannuzzi, Lawrence A.; Spaide, Richard F.] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retina Res Ctr, New York, NY USA.
   [Lima, Luiz H.] Fed Univ Sao Paulo UNIFESP, Dept Ophthalmol, Sao Paulo, Brazil.
C3 Vitreous Retina Macula Consultants of New York; Manhattan Eye Ear &
   Throat Hospital; Universidade Federal de Sao Paulo (UNIFESP)
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 Lima, Luiz H/V-4940-2017; Spaide, Richard/ABD-7368-2020; Freund, K.
   Bailey/V-7488-2018
OI Lima, Luiz H/0000-0001-7304-909X; Freund, K. Bailey/0000-0002-7888-9773
FU LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and
   Throat Hospital; Macula Foundation, Inc.; Topcon Inc.
FX Supported by the LuEsther T. Mertz Retinal Research Center, Manhattan
   Eye, Ear, and Throat Hospital, and the Macula Foundation, Inc.; Dr.
   Spaide receives royalty payments from Topcon Inc. There are no conflicts
   of interest for the other authors.
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NR 25
TC 29
Z9 30
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 2012
VL 32
IS 4
BP 647
EP 651
DI 10.1097/IAE.0b013e31823fb847
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 918ET
UT WOS:000302232800001
PM 22218150
DA 2022-11-30
ER

PT J
AU Zhang, L
   Lim, SL
   Du, HJ
   Zhang, M
   Kozak, I
   Hannum, G
   Wang, XL
   Ouyang, H
   Hughes, G
   Zhao, L
   Zhu, XM
   Lee, C
   Su, ZG
   Zhou, XR
   Shaw, R
   Geum, DH
   Wei, XR
   Zhu, J
   Ideker, T
   Oka, C
   Wang, NL
   Yang, ZL
   Shaw, PX
   Zhang, K
AF Zhang, Li
   Lim, Siok Lam
   Du, Hongjun
   Zhang, Ming
   Kozak, Igor
   Hannum, Gregory
   Wang, Xiaolei
   Ouyang, Hong
   Hughes, Guy
   Zhao, Ling
   Zhu, Xuemei
   Lee, Clara
   Su, Zhiguang
   Zhou, Xinrong
   Shaw, Robert
   Geum, Dongho
   Wei, Xinran
   Zhu, Jin
   Ideker, Trey
   Oka, Chio
   Wang, Ningli
   Yang, Zhenglin
   Shaw, Peter X.
   Zhang, Kang
TI High Temperature Requirement Factor A1 (HTRA1) Gene Regulates
   Angiogenesis through Transforming Growth Factor-beta Family Member
   Growth Differentiation Factor 6
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SERINE-PROTEASE; MACULAR DEGENERATION; MUTATIONS; GDF6; ASSOCIATION;
   EXPRESSION; SPECTRUM; BONE; VEGF; EYE
AB Genome-wide association study (GWAS) has identified genetic variants in the promoter region of the high temperature requirement factor A1 (HTRA1) gene associated with age-related macular degeneration (AMD). As a secreted serine protease, HTRA1 has been reported to interact with members of the transforming growth factor-beta (TGF-beta) family and regulate their signaling pathways. Growth differentiation factor 6 (GDF6), a member of the TGF-beta family, is involved in ectoderm patterning and eye development. Mutations in GDF6 have been associated with abnormal eye development that may result in microphthalmia and anophthalmia. In this report, we identified a single nucleotide polymorphism (SNP) rs6982567 A/G near the GDF6 gene that is significantly associated withAMD(p value = 3.54 x 10(-8)). We demonstrated that the GDF6 AMD risk allele (rs6982567 A) is associated with decreased expression of the GDF6 and increased expression of HTRA1. Similarly, the HTRA1 AMD risk allele (rs10490924 T) is associated with decreased GDF6 and increased HTRA1 expression. We observed decreased vascular development in the retina and significant up-regulation of GDF6 gene in the RPE layer, retinal and brain tissues in HTRA1 knock-out (htra1(-/-)) mice as compared with the wild-type counterparts. Furthermore, we showed enhanced SMAD signaling in htra1(-/-) mice. Our data suggests a critical role of HTRA1 in the regulation of angiogenesis via TGF-beta signaling and identified GDF6 as a novel disease gene for AMD.
C1 [Zhang, Li; Zhang, Ming; Su, Zhiguang; Wei, Xinran; Zhu, Jin; Shaw, Peter X.; Zhang, Kang] Sichuan Univ, Mol Med Res Ctr, W China Hosp, Chengdu 610041, Peoples R China.
   [Zhang, Li; Zhang, Ming; Su, Zhiguang; Wei, Xinran; Zhu, Jin; Shaw, Peter X.; Zhang, Kang] Sichuan Univ, Dept Ophthalmol, W China Hosp, Chengdu 610041, Peoples R China.
   [Zhang, Li; Lim, Siok Lam; Du, Hongjun; Kozak, Igor; Ouyang, Hong; Hughes, Guy; Zhao, Ling; Zhu, Xuemei; Lee, Clara; Zhou, Xinrong; Shaw, Robert; Geum, Dongho; Wei, Xinran; Zhu, Jin; Shaw, Peter X.; Zhang, Kang] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
   [Zhang, Li; Lim, Siok Lam; Du, Hongjun; Kozak, Igor; Ouyang, Hong; Hughes, Guy; Zhao, Ling; Zhu, Xuemei; Lee, Clara; Zhou, Xinrong; Shaw, Robert; Geum, Dongho; Wei, Xinran; Zhu, Jin; Shaw, Peter X.; Zhang, Kang] Univ Calif San Diego, Shiley Eye Ctr, La Jolla, CA 92093 USA.
   [Hannum, Gregory; Ideker, Trey] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Wang, Xiaolei; Wang, Ningli] Tong Ren Eye Hosp, Beijing, Peoples R China.
   [Oka, Chio] Nara Inst Sci & Technol, Div Gene Funct Anim, Nara 6300192, Japan.
   [Yang, Zhenglin] Sichuan Acad Med Sci, Sichuan Prov Key Lab Human Dis Gene Study, Chengdu 610072, Sichuan, Peoples R China.
   [Yang, Zhenglin] Sichuan Acad Med Sci, Inst Lab Med, Chengdu 610072, Sichuan, Peoples R China.
   [Yang, Zhenglin] Sichuan Prov Peoples Hosp, Chengdu 610072, Sichuan, Peoples R China.
C3 Sichuan University; Sichuan University; University of California System;
   University of California San Diego; University of California System;
   University of California San Diego; University of California System;
   University of California San Diego; Nara Institute of Science &
   Technology; Sichuan Provincial People's Hospital; Sichuan Provincial
   People's Hospital; Sichuan Provincial People's Hospital
RP Shaw, PX (通讯作者)，Sichuan Univ, Mol Med Res Ctr, W China Hosp, Chengdu 610041, Peoples R China.
EM pshaw@ucsd.edu; kang.zhang@gmail.com
RI Kozak, Igor/AAC-4645-2019; Zhang, Kang/Y-2740-2019; Su,
   Zhiguang/AFS-0022-2022; Zhao, Ling/D-9005-2015
OI Zhang, Kang/0000-0002-4549-1697; Ouyang, Hong/0000-0002-7622-7733;
   Ideker, Trey/0000-0002-1708-8454; Su, Zhiguang/0000-0001-8635-9310;
   Zhao, Ling/0000-0002-6644-2886
FU NEI; National Basic Research Program of China [2011CB510200]; Chinese
   National 985 Project; Veterans Affairs Merit Award; Research to Prevent
   Blindness; BWF; National Natural Science Foundation of China [81025006];
   NATIONAL EYE INSTITUTE [R01EY021374, R01EY018660] Funding Source: NIH
   RePORTER; Veterans Affairs [I01BX001898] Funding Source: NIH RePORTER
FX This work was supported, in whole or in part, by a National Institutes
   of Health grant from the NEI, National Basic Research Program of China
   Grant 973 Program, No. 2011CB510200, Chinese National 985 Project to
   Sichuan University and West China Hospital, a Veterans Affairs Merit
   Award, Research to Prevent Blindness, and a BWF Clinical Scientist Award
   in Translational Research (to K.Z.).; Supported by National Natural
   Science Foundation of China Grant 81025006. To whom correspondence may
   be addressed. E-mail: zliny@yahoo.com.
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NR 30
TC 65
Z9 68
U1 1
U2 18
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI ROCKVILLE
PA 11200 ROCKVILLE PIKE, SUITE 302, ROCKVILLE, MD, UNITED STATES
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 6
PY 2012
VL 287
IS 2
BP 1520
EP 1526
DI 10.1074/jbc.M111.275990
PG 7
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 877IE
UT WOS:000299170300065
PM 22049084
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Preise, D
   Oren, R
   Glinert, I
   Kalchenko, V
   Jung, S
   Scherz, A
   Salomon, Y
AF Preise, Dina
   Oren, Roni
   Glinert, Itai
   Kalchenko, Vyacheslav
   Jung, Steffen
   Scherz, Avigdor
   Salomon, Yoram
TI Systemic antitumor protection by vascular-targeted photodynamic therapy
   involves cellular and humoral immunity
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Bachteriochlorophyll; Cancer; Immune response; Immunotherapy;
   Photodynamic therapy; Vascular targeting
ID CD8(+) T-CELLS; DENDRITIC CELLS; MELANOMA TUMORS; SELF-PROTEINS; CANCER;
   COMBINATION; RESPONSES; MODEL; MICE; PHOTOIMMUNOTHERAPY
AB Vascular-targeted photodynamic therapy (VTP) takes advantage of intravascular excitation of a photosensitizer (PS) to produce cytotoxic reactive oxygen species (ROS). These ROS are potent mediators of vascular damage inducing rapid local thrombus formation, vascular occlusion, and tissue hypoxia. This light-controlled process is used for the eradication of solid tumors with Pd-bacteriochlorophyll derivatives (Bchl) as PS. Unlike classical photodynamic therapy (PDT), cancer cells are not the primary target for VTP but instead are destroyed by treatment-induced oxygen deprivation. VTP initiates acute local inflammation inside the illuminated area accompanied by massive tumor tissue death. Consequently, in the present study, we addressed the possibility of immune response induction by the treatment that may be considered as an integral part of the mechanism of VTP-mediated tumor eradication. The effect of VTP on the host immune system was investigated using WST11, which is now in phase II clinical trials for age-related macular degeneration and intended to be evaluated for cancer therapy. We found that a functional immune system is essential for successful VTP. Long-lasting systemic antitumor immunity was induced by VTP involving both cellular and humoral components. The antitumor effect was cross-protective against mismatched tumors, suggesting VTP-mediated production of overlapping tumor antigens, possibly from endothelial origin. Based on our findings we suggest that local VTP might be utilized in combination with other anticancer therapies (e.g., immunotherapy) for the enhancement of host antitumor immunity in the treatment of both local and disseminated disease.
C1 [Preise, Dina; Oren, Roni; Glinert, Itai; Salomon, Yoram] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel.
   [Scherz, Avigdor] Weizmann Inst Sci, Dept Plant Sci, IL-76100 Rehovot, Israel.
   [Jung, Steffen] Weizmann Inst Sci, Dept Chem Immunol, IL-76100 Rehovot, Israel.
   [Kalchenko, Vyacheslav] Weizmann Inst Sci, Dept Vet Resources, IL-76100 Rehovot, Israel.
C3 Weizmann Institute of Science; Weizmann Institute of Science; Weizmann
   Institute of Science; Weizmann Institute of Science
RP Salomon, Y (通讯作者)，Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel.
EM yoram.salomon@weizmann.ac.il
RI Jung, Steffen/K-1409-2012; Kalchenko, Vyacheslav/F-2924-2012; Oren,
   Roni/GZN-1527-2022
OI Jung, Steffen/0000-0003-4290-5716; Oren, Roni/0000-0003-1228-412X;
   Kalchenko, Vyacheslav/0000-0002-3166-7049
FU STEBA-BIOTECH ( France)
FX The authors wish to thank Prof. L. Eisenbach and Dr. E. Tzehoval for
   valuable discussions and technical help, to Dr. Ori Brener for
   histopathology work, to Ester Shai, for her technical help. Study
   supported by STEBA-BIOTECH ( France).
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NR 51
TC 67
Z9 76
U1 1
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD JAN
PY 2009
VL 58
IS 1
BP 71
EP 84
DI 10.1007/s00262-008-0527-0
PG 14
WC Oncology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Immunology
GA 364XU
UT WOS:000260369800008
PM 18488222
DA 2022-11-30
ER

PT J
AU Park, JW
   Moon, C
   Yun, S
   Kim, SY
   Bae, YC
   Chun, MH
   Moon, JI
AF Park, Joo Wan
   Moon, Cheil
   Yun, Sunmi
   Kim, So Yeun
   Bae, Yong Chul
   Chun, Myung-Hoon
   Moon, Jung-Il
TI Differential expression of heat shock protein mRNAs under in vivo
   glutathione depletion in the mouse retina
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE oxidative stress; retina; glutathione; BSO; heat shock protein
ID NORMAL RAT EYE; OXIDATIVE STRESS; GANGLION-CELLS; TNF-ALPHA; HSP27;
   HEAT-SHOCK-PROTEIN-70; PROTECTION; INCREASE; HSP70; IMMUNOREACTIVITY
AB Heat shock proteins (HSPs) are highly conserved proteins playing a protective role under deleterious conditions caused by a wide variety of pathophysiological, including environmental stresses. 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 induced cell death in the retina, but the mechanism(s) of cellular protection were not clear. Unregulated oxidative stress was induced by depletion of intracellular GSH by systematic administration of buthionine sulphoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase. After 0, 1, 4 and 7 days of BSO administration, we examined expression of both large and small HSP mRNAs (hsp90 alpha, hsp9 beta, hsp70, hsp60 and hsp25) in oxidative-stressed mouse retina. Of large HSPs, only hsp70 expression was significantly decreased from 1 day after BSO injection, whereas expression of other large hsps was not changed on day 1. Expression of hsp60 decreased on 4 days, whereas expression of hsp90 decreased on 7 days after BSO administration. Different from large HSPs, a small HSP, hsp25 increased its expression to a great extent from 1 day after BSO administration. Taken together, our results show that unregulated oxidative stress could induce differential expression of HSPs, which, in turn, may play distinct roles in the cellular defense. Targeting HSPs, therefore, may provide novel tools for treatment of retinal degenerative diseases such as glaucoma, retinopathy or age-related macular degeneration. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
C1 Catholic Univ Korea, Coll Med, Dept Ophthalmol, Seoul 150713, South Korea.
   Catholic Univ Korea, Coll Med, Dept Anat, Seoul 150713, South Korea.
   Kyungpook Natl Univ, Sch Dent, Dept Oral Anat & Neurobiol, Taegu 702701, South Korea.
   Kyungpook Natl Univ, Sch Dent, BrainKorea21, Taegu 702701, South Korea.
C3 Catholic University of Korea; Catholic University of Korea; Kyungpook
   National University; Kyungpook National University
RP Moon, JI (通讯作者)，Catholic Univ Korea, Coll Med, Dept Ophthalmol, 62 Yeouido, Seoul 150713, South Korea.
EM jimoon@catholic.ac.kr
OI Moon, Cheil/0000-0002-9741-7229
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NR 37
TC 20
Z9 21
U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD FEB 21
PY 2007
VL 413
IS 3
BP 260
EP 264
DI 10.1016/j.neulet.2006.11.052
PG 5
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 143ZB
UT WOS:000244763800017
PM 17197086
DA 2022-11-30
ER

PT J
AU Balaggan, KS
   Binley, K
   Esapa, M
   MacLaren, RE
   Iqball, S
   Duran, Y
   Pearson, RA
   Kan, O
   Barker, SE
   Smith, AJ
   Bainbridge, JWB
   Naylor, S
   Ali, RR
AF Balaggan, K. S.
   Binley, K.
   Esapa, M.
   MacLaren, R. E.
   Iqball, S.
   Duran, Y.
   Pearson, R. A.
   Kan, O.
   Barker, S. E.
   Smith, A. J.
   Bainbridge, J. W. B.
   Naylor, S.
   Ali, R. R.
TI EIAV vector-mediated delivery of endostatin or angiostatin inhibits
   angiogenesis and vascular hyperpermeability in experimental CNV
SO GENE THERAPY
LA English
DT Article
DE EIAV; angiostatin; endostatin; choroidal neovascularisation; apoptosis;
   permeability
ID ENDOTHELIAL GROWTH-FACTOR; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION;
   EQUINE INFECTIOUS-ANEMIA; GENE-TRANSFER; LENTIVIRAL VECTOR;
   DOWN-REGULATION; NERVOUS-SYSTEM; CELL-ADHESION; EXPRESSION; VEGF
AB We evaluated the efficacy of equine infectious anaemia virus (EIAV)-based lentiviral vectors encoding endostatin (EIAV. endostatin) or angiostatin ( EIAV. angiostatin) in inhibiting angiogenesis and vascular hyperpermeability in the laser-induced model of choroidal neovascularisation (CNV). Equine infectious anaemia virus. endostatin, EIAV. angiostatin or control ( EIAV. null) vectors were administered into the subretinal space of C57BI/6J mice. Two weeks after laser injury CNV areas and the degree of vascular hyperpermeability were measured by image analysis of in vivo fluorescein angiograms. Compared with EIAV.null-injected eyes, EIAV. endostatin resulted in a 59.5% (P < 0.001) reduction in CNV area and a reduction in hyperpermeability of 25.6% ( P < 0.05). Equine infectious anaemia virus. angiostatin resulted in a 50.0% (P < 0.05) reduction in CNV area and a 23.9% (P < 0.05) reduction in hyperpermeability. Equine infectious anaemia virus. endostatin, but not EIAV. angiostatin significantly augmented the frequency of apoptosis within the induced CNV as compared with injected controls. TdT-dUTP terminal nick end labeling analysis 5 weeks post-injection, and histological and retinal flatmount analysis 12 months post-injection revealed no evidence of vector- or transgene expression-related deleterious effects on neurosensory retinal cells, or mature retinal vasculature in non-lasered eyes. Highly expressing EIAV-based vectors encoding endostatin or angiostatin effectively control angiogenesis and hyperpermeability in experimental CNV without long-term deleterious effects, supporting the use of such a strategy in the management of patients with exudative age-related macular degeneration.
C1 Inst Ophthalmol, Div Mol Therapy, London EC1V 9EL, England.
   Oxford BioMed UK Ltd, Biol Syst Grp, Medawar Ctr, Oxford, England.
   Inst Child Hlth, Dept Biol Unit, London WC1, England.
C3 University of London; University College London; Oxford Biomedica (UK)
   Ltd
RP Ali, RR (通讯作者)，Inst Ophthalmol, Div Mol Therapy, 11-43 Bath St, London EC1V 9EL, England.
EM kambalaggan@yahoo.co.uk; r.ali@ucl.ac.uk
RI Smith, Alexander/A-5142-2009; Pearson, Rachael/Y-3339-2018
OI Pearson, Rachael/0000-0002-1107-1969; Ali, Robin/0000-0003-3126-6517;
   MacLaren, Robert/0000-0002-3096-4682; Bainbridge,
   James/0000-0003-1318-8201
FU Medical Research Council [G0601588] Funding Source: Medline
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NR 53
TC 47
Z9 53
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
EI 1476-5462
J9 GENE THER
JI Gene Ther.
PD AUG
PY 2006
VL 13
IS 15
BP 1153
EP 1165
DI 10.1038/sj.gt.3302769
PG 13
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity; Research & Experimental Medicine
GA 064JJ
UT WOS:000239084800005
PM 16572190
DA 2022-11-30
ER

PT J
AU Jiang, YD
   Duan, LJ
   Pi, JB
   Le, YZ
   Fong, GH
AF Jiang, Yida
   Duan, Li-Juan
   Pi, Jingbo
   Le, Yun-Zheng
   Fong, Guo-Hua
TI Dependence of Retinal Pigment Epithelium Integrity on the NRF2-Heme
   Oxygenase-1 Axis
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE oxidative stress; NRF2; heme oxygenase-1; retinal pigment epithelial
   cells; tight junctions; age-related macular degeneration
ID HEME OXYGENASE-1; OXIDATIVE STRESS; NF-E2-RELATED FACTOR-2;
   TRANSCRIPTION FACTOR; SPECIES GENERATION; SODIUM IODATE; CELL-DEATH; RPE
   CELLS; NRF2; EXPRESSION
AB PURPOSE. Tight junctions (TJs) form the structural basis of retinal pigment epithelium (RPE) barrier functions. Although oxidative stress contributes to age-related macular degeneration, it is unclear how RPE TJ integrity is controlled by redox balance. In this study, we investigated the protective roles of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor, and heme oxygenase-1 (HO1), a heme-degrading enzyme encoded by the NRF2 target gene HMOX1. METHODS. ARPE19 cell cultures and mice, including wild-type, Nrf2-/-, and RPE-specific NRF2-deficient mice, were treated with chemicals that impose oxidative stress or impact heme metabolism. In addition, NRF2 and HO1 expression in ARPE19 cells was knocked down by siRNA. TJ integrity was examined by anti-zonula occludens-1 staining of cultured cells or flatmount RPE tissues from mice. RPE barrier functions were evalu-ated by transepithelium electrical resistance in ARPE19 cells and immunofluorescence staining for albumin or dextran in eye histological sections. RESULTS. TJ structures and RPE barrier functions were compromised due to oxidant expo-sure and NRF2 deficiency but were rescued by HO1 inducer. Furthermore, treatment with HO1 inhibitor or heme precursor is destructive to TJ structures and RPE barrier proper-ties. Interestingly, both NRF2 and HO1 were upregulated under oxidative stress, probably as an adaptive response to mitigate oxidant-inflicted damages. CONCLUSIONS. Our data indicate that the NRF2-HO1 axis protects TJ integrity and RPE barrier functions by driving heme degradation.
C1 [Jiang, Yida; Duan, Li-Juan; Fong, Guo-Hua] Univ Connecticut Hlth Ctr, Ctr Vasc Biol, Farmington, CT USA.
   [Jiang, Yida; Fong, Guo-Hua] Univ Connecticut Hlth Ctr, Dept Cell Biol, Farmington, CT USA.
   [Pi, Jingbo] China Med Univ, Sch Publ Hlth, Shenyang, Liaoning, Peoples R China.
   [Le, Yun-Zheng] Univ Oklahoma Hlth Sci Ctr, Harold Hamm Oklahoma Diabet Ctr, Dept Med, Cell Biol Ophthalmol, Oklahoma City, OK USA.
   [Fong, Guo-Hua] Univ Connecticut Hlth Ctr, Ctr Vasc Biol, 263 Farmington Ave, Farmington, CT 06030 USA.
C3 University of Connecticut; University of Connecticut; China Medical
   University; University of Oklahoma System; University of Oklahoma Health
   Sciences Center; University of Connecticut
RP Fong, GH (通讯作者)，Univ Connecticut Hlth Ctr, Ctr Vasc Biol, 263 Farmington Ave, Farmington, CT 06030 USA.
EM fong@uchc.edu
RI PI, JINGBO/GWC-2514-2022
OI PI, JINGBO/0000-0003-0227-8041
FU National Institutes of Health [1R01EY031593, 2R01EY019721]
FX Acknowledgments Supported by grants from the National Institutes of
   Health (1R01EY031593 and 2R01EY019721) .
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NR 76
TC 0
Z9 0
U1 1
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 AUG
PY 2022
VL 63
IS 9
AR 30
DI 10.1167/iovs.63.9.30
PG 17
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4L4GC
UT WOS:000852586600008
PM 36036912
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Li, JPO
   Liu, HR
   Ting, DSJ
   Jeon, S
   Chan, RVP
   Kim, JE
   Sim, DA
   Thomas, PBM
   Lin, HT
   Chen, YX
   Sakomoto, T
   Loewenstein, A
   Lam, DSC
   Pasquale, LR
   Wong, TY
   Lam, LA
   Ting, DSW
AF Li, Ji-Peng Olivia
   Liu, Hanruo
   Ting, Darren S. J.
   Jeon, Sohee
   Chan, R. V. Paul
   Kim, Judy E.
   Sim, Dawn A.
   Thomas, Peter B. M.
   Lin, Haotian
   Chen, Youxin
   Sakomoto, Taiji
   Loewenstein, Anat
   Lam, Dennis S. C.
   Pasquale, Louis R.
   Wong, Tien Y.
   Lam, Linda A.
   Ting, Daniel S. W.
TI Digital technology, tele-medicine and artificial intelligence in
   ophthalmology: A global perspective
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Telemedicine; Tele-ophthalmology; Tele-screening; Diabetic retinopathy
   screening; Artificial intelligence; Deep learning; Digital
   transformation; Digital innovations; COVID-19; Digital technology
ID PHILADELPHIA GLAUCOMA DETECTION; MACHINE LEARNING CLASSIFIERS;
   STANFORD-UNIVERSITY NETWORK; NATIONAL SCREENING-PROGRAM; IMAGE
   ASSESSMENT SOFTWARE; VISUAL-FIELD PROGRESSION; MAJOR RISK-FACTORS;
   PRIMARY OPEN-ANGLE; DIABETIC-RETINOPATHY; MACULAR DEGENERATION
AB The simultaneous maturation of multiple digital and telecommunications technologies in 2020 has created an unprecedented opportunity for ophthalmology to adapt to new models of care using tele-health supported by digital innovations. These digital innovations include artificial intelligence (AI), 5th generation (5G) telecommunication networks and the Internet of Things (IoT), creating an inter-dependent ecosystem offering opportunities to develop new models of eye care addressing the challenges of COVID-19 and beyond. Ophthalmology has thrived in some of these areas partly due to its many image-based investigations. Tele-health and AI provide synchronous solutions to challenges facing ophthalmologists and healthcare providers worldwide. This article reviews how countries across the world have utilised these digital innovations to tackle diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, glaucoma, refractive error correction, cataract and other anterior segment disorders. The review summarises the digital strategies that countries are developing and discusses technologies that may increasingly enter the clinical workflow and processes of ophthalmologists. Furthermore as countries around the world have initiated a series of escalating containment and mitigation measures during the COVID-19 pandemic, the delivery of eye care services globally has been significantly impacted. As ophthalmic services adapt and form a "new normal", the rapid adoption of some of telehealth and digital innovation during the pandemic is also discussed. Finally, challenges for validation and clinical implementation are considered, as well as recommendations on future directions.
C1 [Li, Ji-Peng Olivia] Moorfields Eye Hosp NHS Fdn Trust, London, England.
   [Liu, Hanruo] Beijing Tongren Hosp, Beijing, Peoples R China.
   [Liu, Hanruo] Capital Med Univ, Beijing, Peoples R China.
   [Liu, Hanruo] Beijing Inst Ophthalmol, Beijing, Peoples R China.
   [Ting, Darren S. J.] Univ Nottingham, Acad Ophthalmol, Nottingham, England.
   [Jeon, Sohee] Keye Eye Ctr, Seoul, South Korea.
   [Chan, R. V. Paul] Univ Illinois, Chicago, IL USA.
   [Kim, Judy E.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
   [Sim, Dawn A.; Thomas, Peter B. M.] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr Ophthalmol, London, England.
   [Sim, Dawn A.; Thomas, Peter B. M.] UCL Inst Ophthalmol, London, England.
   [Lin, Haotian] Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China.
   [Chen, Youxin] Peking Union Med Coll Hosp, Beijing, Peoples R China.
   [Sakomoto, Taiji] Kagoshima Univ, Dept Ophthalmol, Grad Sch Med & Dent Sci, Kagoshima, Japan.
   [Loewenstein, Anat] Tel Aviv Med Ctr & Sch Med, Dept Ophthalmol, Tel Aviv, Israel.
   [Lam, Dennis S. C.] C Mer Int Eye Care Grp Ltd, C MER Dennis Lam Eye Ctr, Hong Kong, Peoples R China.
   [Lam, Dennis S. C.] Chinese Univ Hong Kong Shenzhen, Int Eye Res Inst, Shenzhen, Peoples R China.
   [Pasquale, Louis R.] Icahn Sch Med Mt Sinai, Dept Ophthalmol, New York, NY 10029 USA.
   [Wong, Tien Y.; Ting, Daniel S. W.] Duke NUS Med Sch Singapore, Singapore Natl Eye Ctr, Singapore, Singapore.
   [Lam, Linda A.] Univ Southern Calif, Keck Sch Med, USC Roski Eye Inst, Los Angeles, CA 90007 USA.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; Capital Medical University; Capital Medical
   University; University of Nottingham; University of Illinois System;
   University of Illinois Chicago; University of Illinois Chicago Hospital;
   Medical College of Wisconsin; University of London; University College
   London; Moorfields Eye Hospital NHS Foundation Trust; University of
   London; University College London; Chinese Academy of Medical Sciences -
   Peking Union Medical College; Peking Union Medical College Hospital;
   Kagoshima University; Tel Aviv University; Sackler Faculty of Medicine;
   Chinese University of Hong Kong, Shenzhen; Icahn School of Medicine at
   Mount Sinai; National University of Singapore; Singapore National Eye
   Center; University of Southern California
RP Ting, DSW (通讯作者)，Singapore Natl Eye Ctr, 11 Third Hosp Ave, Singapore 168751, Singapore.
EM daniel.ting.s.w@singhealth.com.sg
RI Wong, Tien Yin/AAC-9724-2020; zhang, zeyu/GLR-4184-2022
OI Wong, Tien Yin/0000-0002-8448-1264; Thomas, Peter/0000-0003-1681-7659;
   Li, Ji-Peng Olivia/0000-0001-8130-2913; Bidwai, Pooja
   Vishal/0000-0002-3077-4395
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TC 97
Z9 99
U1 69
U2 221
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 100900
DI 10.1016/j.preteyeres.2020.100900
EA JUN 2021
PG 32
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA TE5UC
UT WOS:000670077000003
PM 32898686
OA Green Published, Bronze
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Krestanova, A
   Kubicek, J
   Penhaker, M
AF Krestanova, Alice
   Kubicek, Jan
   Penhaker, Marek
TI Recent Techniques and Trends for Retinal Blood Vessel Extraction and
   Tortuosity Evaluation: A Comprehensive Review
SO IEEE ACCESS
LA English
DT Review
DE Biomedical imaging; Retina; Blood vessels; Databases; Image
   segmentation; Retinopathy; Review; retinal blood vessels; fundus camera;
   RetCam; retinopathy of prematurity; diabetic retinopathy
ID MATCHED-FILTER; VASCULAR TORTUOSITY; NEURAL-NETWORK; SEGMENTATION;
   IMAGES; DELINEATION; MODEL
AB Retinal blood vessel segmentation plays an important part in the early diagnosis and treatment of eye disease. It is a tool for ophthalmologists. Many diseases can be identified by examining manifestations and images of blood vessels, including diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, retinopathy due to hypertension, glaucoma and others. Early detection allows physicians to provide patients with effective treatment, while in the opposite case, the late detection of retinal disease can ultimately lead to blindness. One of the indices when examining the retina is an evaluation of blood vessels based on tortuosity, i.e. the degree of curvature of blood vessels. This article presents a comprehensive overview of all segmentation techniques for retinal blood vessel extraction from images taken with a fundus camera in adults and older children or with a RetCam fundus camera in new-borns and younger children over the last 10 years. An integral part of this review is a comprehensive overview with information on all available public and private databases with retinal images. The review includes an evaluation of segmentation techniques based on objectivization parameters, including information on all objectivization parameters used in this article. As already mentioned, the degree of curvature of retinal blood vessels is used to classify severity of blood vessels tortuosity. There is no uniform metric for determining tortuosity, but this review presents a comprehensive overview of all metrics and calculations used to determine the degree of tortuosity of retinal blood vessels.
C1 [Krestanova, Alice; Kubicek, Jan; Penhaker, Marek] VSB Tech Univ Ostrava, Dept Cybernet & Biomed Engn, Ostrava 70800, Czech Republic.
C3 Technical University of Ostrava
RP Krestanova, A (通讯作者)，VSB Tech Univ Ostrava, Dept Cybernet & Biomed Engn, Ostrava 70800, Czech Republic.
EM alice.krestanova@vsb.cz
RI Penhaker, Marek/C-3751-2016
OI Penhaker, Marek/0000-0001-9527-4642; Varysova, Alice/0000-0002-2788-7794
FU Project Biomedical Engineering Systems XVI [SP2020/55]; Czech Science
   Foundation (TACR) 440 ETA [TL01000302]
FX This work was supported in part by the Project Biomedical Engineering
   Systems XVI, under Grant SP2020/55, and in part by the research project
   The Czech Science Foundation (TACR) 440 ETA under Grant TL01000302
   (Medical Devices Development as an Effective Investment for Public and
   Private).
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NR 159
TC 2
Z9 2
U1 7
U2 28
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2169-3536
J9 IEEE ACCESS
JI IEEE Access
PY 2020
VL 8
BP 197787
EP 197816
DI 10.1109/ACCESS.2020.3033027
PG 30
WC Computer Science, Information Systems; Engineering, Electrical &
   Electronic; Telecommunications
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Telecommunications
GA OR8ZC
UT WOS:000589754600001
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Horita, S
   Watanabe, M
   Katagiri, M
   Nakamura, H
   Haniuda, H
   Nakazato, T
   Kagawa, Y
AF Horita, Shinya
   Watanabe, Miwa
   Katagiri, Mai
   Nakamura, Hiroaki
   Haniuda, Hiroki
   Nakazato, Tomoyuki
   Kagawa, Yoshiyuki
TI Species differences in ocular pharmacokinetics and pharmacological
   activities of regorafenib and pazopanib eye-drops among rats, rabbits
   and monkeys
SO PHARMACOLOGY RESEARCH & PERSPECTIVES
LA English
DT Article
DE age-related macular degeneration; eye-drop; ocular pharmacokinetics and
   pharmacological activities; pazopanib; regorafenib; species differences;
   vascular endothelial growth factor
ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; VEGF
   TRAP; RANIBIZUMAB; DELIVERY; BEVACIZUMAB; PREVENTION; PEGAPTANIB;
   EFFICACY; UPDATE
AB Age-related macular degeneration (AMD) is the leading cause of severe vision impairment in patients over the age of 60 years. Choroidal neovascularization (CNV) is the hallmark of neovascular AMD and vascular endothelial growth factor (VEGF) plays a causal role in the formation of CNV. Although regorafenib and pazopanib, small molecule VEGF receptor (VEGFR) inhibitors, were developed as eye-drops, their efficacies were insufficient in clinical. In this study, we evaluated ocular pharmacokinetics and pharmacological activities of regorafenib and pazopanib after ocular instillation in multiple animal species. In rats, both regorafenib and pazopanib showed high enough concentrations in the posterior eye tissues to inhibit VEGFR. In laser-induced rat CNV model, regorafenib showed clear reduction in CNV area. On the other hand, the concentrations of regorafenib and pazopanib in the posterior eye tissues were much lower after ocular instillation in rabbits and monkeys compared to those in rats. Pazopanib did not show any improvement in monkey model. Regorafenib was nano-crystalized to improve its drug delivery to the posterior eye tissues. The nano-crystalized formulation of regorafenib showed higher concentrations in the posterior segments in rabbits compared to its microcrystal suspension. From these studies, large interspecies differences were found in ocular delivery to the posterior segments after ocular instillation. Such large interspecies difference could be the reason for the insufficient efficacies of regorafenib and pazopanib in clinical studies. Nanocrystallization was suggested to be one of the effective ways to overcome this issue.
C1 [Horita, Shinya; Watanabe, Miwa; Katagiri, Mai; Nakamura, Hiroaki] Kyowa Kirin Co Ltd, R&D Div, 1188 Shimotogari, Shizuoka 4118731, Japan.
   [Horita, Shinya; Kagawa, Yoshiyuki] Univ Shizuoka, Sch Pharmaceut Sci, Dept Clin Pharmaceut, Shizuoka, Japan.
   [Haniuda, Hiroki; Nakazato, Tomoyuki] Kyowa Kirin Co Ltd, Prod Div, Shizuoka, Japan.
C3 Kyowa Kirin Ltd; University of Shizuoka; Kyowa Kirin Ltd
RP Horita, S (通讯作者)，Kyowa Kirin Co Ltd, R&D Div, 1188 Shimotogari, Shizuoka 4118731, Japan.
EM shinya.horita.qe@kyowakirin.com
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NR 39
TC 11
Z9 11
U1 0
U2 2
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 2052-1707
J9 PHARMACOL RES PERSPE
JI Pharmacol. Res. Perspect.
PD DEC
PY 2019
VL 7
IS 6
AR e00545
DI 10.1002/prp2.545
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA KK8OU
UT WOS:000512996500021
PM 31763044
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Rong, X
   Tian, H
   Yang, L
   Li, W
AF Rong, Xin
   Tian, Hong
   Yang, Liu
   Li, Wei
TI Function-first ligandomics for ocular vascular research and drug target
   discovery
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retina; Vascular disease; Ligandomics; Comparative ligandomics;
   Angiogenic factor; Vascular leakage factor; Drug target discovery;
   Target validation
ID MACULAR DEGENERATION; EFFICIENT IDENTIFICATION; BINDING PROTEINS;
   RANIBIZUMAB; BEVACIZUMAB; ENDOTHELIUM; VEGF; AFLIBERCEPT; RETINOPATHY;
   GROWTH
AB Human eyes may develop different vascular diseases with neovascularization and/or leakage, including wet age-related macular degeneration (AMD), diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), retinopathy of prematurity, corneal neovascularization and intraocular tumors. A breakthrough in therapy is the advent and approval of vascular endothelial growth factor (VEGF) inhibitors. However, anti-VEGF drugs not only have limited efficacy to treat AMD, DME and PDR but also are not approved for other ocular indications. The key to addressing these unmet clinical needs is to develop novel therapies against VEGF-independent angiogenic factors or signaling pathways for alternative or combination therapy. We recently developed the first paradigm of ligandomics for global mapping of cell-wide ligands as well as disease-selective ligands. Therapies targeting disease-selective angiogenic or vascular leakage factors likely have high efficacy, minimal side effects, wide therapeutic windows and relatively low drug attrition rates. A critical challenge is how to distinguish between genuine drug targets and spurious hits identified by high-throughput ligandomics. Here we exploited the unique advantages of the eye and extracellular ligands by combining ligandomics with "function-first" and/ or "therapy-first" analyses to efficiently characterize functional activity, disease selectivity, pathogenic role and therapeutic potential of identified ligands. The innovative function- or therapy-first ligandomics will systematically and reliably delineate disease-selective angiogenic or vascular leakage factors and markedly facilitate ocular vascular research and ligand-guided targeted anti-angiogenic therapy.
C1 [Rong, Xin; Li, Wei] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA.
   [Rong, Xin; Yang, Liu] Peking Univ, Dept Ophthalmol, Hosp 1, Beijing, Peoples R China.
   [Tian, Hong] LigandomicsRx LLC, 9177 SW 72nd Ave, Miami, FL 33156 USA.
C3 Bascom Palmer Eye Institute; University of Miami; Peking University
RP Tian, H (通讯作者)，LigandomicsRx LLC, 9177 SW 72nd Ave, Miami, FL 33156 USA.; Li, W (通讯作者)，Univ Miami, Sch Med, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami, FL 33136 USA.
EM h.tian@ligandomicsrx.com; w.li@med.miami.edu
FU NIH [R24EY028764-01A1, R01EY027749-01A1, R21EY027065, R41EY027665-01A1,
   P30-EY014801]; American Diabetes Association Innovative Basic Science
   Award [1-18-IBS-172]; Research to Prevent Blindness; National Natural
   Science Foundation of China [81670841]; NATIONAL EYE INSTITUTE
   [R24EY028764, R41EY027665, R01EY027749, P30EY014801, R21EY027065]
   Funding Source: NIH RePORTER
FX This work was supported by NIH grants (#R24EY028764-01A1,
   R01EY027749-01A1, R21EY027065, R41EY027665-01A1 and P30-EY014801),
   American Diabetes Association Innovative Basic Science Award
   (#1-18-IBS-172), an institutional grant from Research to Prevent
   Blindness, and a grant from the National Natural Science Foundation of
   China (No. 81670841).
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NR 49
TC 9
Z9 9
U1 0
U2 3
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 MAY
PY 2019
VL 182
BP 57
EP 64
DI 10.1016/j.exer.2019.03.009
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HY6RV
UT WOS:000468258300007
PM 30904565
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Savige, J
   Amos, L
   Ierino, F
   Mack, HG
   Symons, RCA
   Hughes, P
   Nicholls, K
   Colville, D
AF Savige, J.
   Amos, L.
   Ierino, Frank
   Mack, H. G.
   Symons, R. C. Andrew
   Hughes, P.
   Nicholls, K.
   Colville, D.
TI Retinal disease in the C3 glomerulopathies and the risk of impaired
   vision
SO OPHTHALMIC GENETICS
LA English
DT Review
DE C3 glomerulopathy; complement alternative pathway; complement factor H;
   dense deposit disease; drusen; membranoproliferative glomerulonephritis
   type II
ID DENSE DEPOSIT DISEASE; COMPLEMENT FACTOR-H; GLOMERULONEPHRITIS TYPE-II;
   MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; MACULAR DEGENERATION; CODING
   VARIANT; DRUSEN; CFH; ECULIZUMAB; MUTATION
AB Background: Dense deposit disease and atypical hemolytic uremic syndrome are often caused by Complement Factor H (CFH) mutations. This study describes the retinal abnormalities in dense deposit disease and, for the first time, atypical haemolytic uremic syndrome. It also reviews our understanding of drusen pathogenesis and their relevance for glomerular disease. Methods: Six individuals with dense deposit disease and one with atypical haemolytic uremic syndrome were studied from 2 to 40 years after presentation. Five had renal transplants. All four who had genetic testing had CFH mutations. Individuals underwent ophthalmological review and retinal photography, and in some cases, optical coherence tomography, and further tests of retinal function. Results: All subjects with dense deposit disease had impaired night vision and retinal drusen or whitish-yellow deposits. Retinal atrophy, pigmentation, and hemorrhage were common. In late disease, peripheral vision was restricted, central vision was distorted, and there were scotoma from sub-retinal choroidal neovascular membranes and atypical serous retinopathy. Drusen were present but less prominent in the young person with atypical uremic syndrome due to a heterozygous CFH mutation. Conclusions: Drusen are common in forms of C3 glomerulopathy caused by compound heterozygous or heterozygous CFH mutations. They are useful diagnostically but also impair vision. Drusen have an identical composition to glomerular deposits. They are also identical to the drusen of age-related macular degeneration, and may respond to the same treatments. Individuals with a C3 glomerulopathy should be assessed ophthalmologically at diagnosis, and monitored regularly for vision-threatening complications.
C1 [Savige, J.; Amos, L.; Colville, D.] Univ Melbourne, Melbourne Hlth, Dept Med, Grattan St, Parkville, Vic 3050, Australia.
   [Savige, J.; Amos, L.; Colville, D.] Royal Melbourne Hosp, Northern Hlth, Grattan St, Parkville, Vic 3050, Australia.
   [Savige, J.; Hughes, P.; Nicholls, K.] Royal Melbourne Hosp, Dept Nephrol, Parkville, Vic, Australia.
   [Ierino, Frank] Austin Hlth, Dept Nephrol, Heidelberg, Vic, Australia.
   [Mack, H. G.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Dept Ophthalmol, East Melbourne, Vic, Australia.
   [Symons, R. C. Andrew] Royal Melbourne Hosp, Dept Ophthalmol, Parkville, Vic, Australia.
   [Symons, R. C. Andrew] Univ Melbourne, Royal Melbourne Hosp, Dept Surg, Parkville, Vic, Australia.
C3 University of Melbourne; Royal Melbourne Hospital; Royal Melbourne
   Hospital; Austin Research Institute; Florey Institute of Neuroscience &
   Mental Health; Royal Victorian Eye & Ear Hospital; University of
   Melbourne; Royal Melbourne Hospital; Royal Melbourne Hospital;
   University of Melbourne
RP Savige, J (通讯作者)，Univ Melbourne, Melbourne Hlth, Dept Med, Grattan St, Parkville, Vic 3050, Australia.; Savige, J (通讯作者)，Royal Melbourne Hosp, Northern Hlth, Grattan St, Parkville, Vic 3050, Australia.
EM jasavige@unimelb.edu.au
RI Symons, Robert Charles Andrew/C-2040-2017; Nicholls,
   Kathleen/N-5002-2017
OI Symons, Robert Charles Andrew/0000-0002-8104-881X; Nicholls,
   Kathleen/0000-0002-1297-8722
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NR 59
TC 12
Z9 12
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1381-6810
EI 1744-5094
J9 OPHTHALMIC GENET
JI Ophthalmic Genet.
PY 2016
VL 37
IS 4
BP 369
EP 376
DI 10.3109/13816810.2015.1101777
PG 8
WC Genetics & Heredity; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Ophthalmology
GA EC0HQ
UT WOS:000387780700003
PM 26915021
DA 2022-11-30
ER

PT J
AU Grover, AK
   Samson, SE
AF Grover, Ashok K.
   Samson, Sue E.
TI Antioxidants and vision health: facts and fiction
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE Eye diseases; Nutritional supplements; Alternative medicine; Cataract;
   Glaucoma; Age-related macular degeneration
ID GINKGO-BILOBA EXTRACT; VITAMIN-E SUPPLEMENTATION; OPEN-ANGLE GLAUCOMA;
   N-ACETYLCARNOSINE; OXIDATIVE STRESS; MACULAR DEGENERATION;
   DIABETIC-RETINOPATHY; RETINITIS-PIGMENTOSA; VISUAL IMPAIRMENT;
   PREVENTION
AB A number of nutritional supplements containing antioxidants are advertised for better vision health. Do they benefit the average consumer? The literature was examined for the effectiveness of antioxidants for human eye health, and for the intricacies in collection of such evidence. The following diseases were considered: cataract, glaucoma, age-related macular degeneration (AMD), retinopathy, retinitis pigmentosa, eye infections, and uveitis. The literature indicates that antioxidant supplements plus lutein have a reasonable probability of retarding AMD. For glaucoma, such supplements were ineffectual in some studies but useful in others. In some studies, antioxidant rich fruits and vegetables were also useful for protection against glaucoma. For diabetic retinopathy, antioxidant supplements may have a small benefit, if any, but only as an adjunct to glycemic control. In very high-risk premature retinopathy and retinitis pigmentosa, antioxidant supplements may be beneficial but those with excess Vitamin E should be avoided. For cataract, there is no evidence for an advantage of such nutritional supplements. However, lubricant drops containing N-acetylcarnosine may be helpful in initial stages of the disease. For eye infections and other causes of uveitis, antioxidants have not been found useful. We recommend that a diet high in antioxidant rich foods should be developed as a habit from an early age. However, when initial signs of vision health deterioration are observed, the appropriate nutritional supplement products may be recommended but only to augment the primary medical treatments.
C1 [Grover, Ashok K.; Samson, Sue E.] McMaster Univ, Dept Med, Hamilton, ON L8N 3Z5, Canada.
   [Grover, Ashok K.] McMaster Univ, Dept Biol, Hamilton, ON L8N 3Z5, Canada.
C3 McMaster University; McMaster University
RP Grover, AK (通讯作者)，McMaster Univ, Dept Med, Hamilton, ON L8N 3Z5, Canada.
EM groverak@mcmaster.ca
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NR 65
TC 26
Z9 28
U1 0
U2 46
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
EI 1573-4919
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD MAR
PY 2014
VL 388
IS 1-2
BP 173
EP 183
DI 10.1007/s11010-013-1908-z
PG 11
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA AD0ZS
UT WOS:000332964100015
PM 24311110
DA 2022-11-30
ER

PT J
AU Chen, M
   Glenn, JV
   Dasari, S
   McVicar, C
   Ward, M
   Colhoun, L
   Quinn, M
   Bierhaus, A
   Xu, HP
   Stitt, AW
AF Chen, Mei
   Glenn, Josephine V.
   Dasari, Shilpa
   McVicar, Carmel
   Ward, Michael
   Colhoun, Liza
   Quinn, Michael
   Bierhaus, Angelika
   Xu, Heping
   Stitt, Alan W.
TI RAGE Regulates Immune Cell Infiltration and Angiogenesis in Choroidal
   Neovascularization
SO PLOS ONE
LA English
DT Article
ID GLYCATION END-PRODUCTS; BRUCHS MEMBRANE; ENDOTHELIAL-CELLS; RECEPTOR
   RAGE; RD8 MUTATION; CRB1 GENE; AGE; MACROPHAGES; MOUSE; ACCUMULATION
AB Purpose: RAGE regulates pro-inflammatory responses in diverse cells and tissues. This study has investigated if RAGE plays a role in immune cell mobilization and choroidal neovascular pathology that is associated with the neovascular form of age-related macular degeneration (nvAMD).
   Methods: RAGE null (RAGE-/-) mice and age-matched wild type (WT) control mice underwent laser photocoagulation to generate choroidal neovascularization (CNV) lesions which were then analyzed for morphology, S100B immunoreactivity and inflammatory cell infiltration. The chemotactic ability of bone marrow derived macrophages (BMDMs) towards S100B was investigated.
   Results: RAGE expression was significantly increased in the retina during CNV of WT mice (p<0.001). RAGE-/- mice exhibited significantly reduced CNV lesion size when compared to WT controls (p<0.05). S100B mRNA was upregulated in the lasered WT retina but not RAGE-/- retina and S100B immunoreactivity was present within CNV lesions although levels were less when RAGE-/- mice were compared to WT controls. Activated microglia in lesions were considerably less abundant in RAGE-/- mice when compared to WT counterparts (p<0.001). A dose dependent chemotactic migration was observed in BMDMs from WT mice (p<0.05-0.01) but this was not apparent in cells isolated from RAGE-/- mice.
   Conclusions: RAGE-S100B interactions appear to play an important role in CNV lesion formation by regulating pro-inflammatory and angiogenic responses. This study highlights the role of RAGE in inflammation-mediated outer retinal pathology.
C1 [Chen, Mei; Glenn, Josephine V.; Dasari, Shilpa; McVicar, Carmel; Ward, Michael; Colhoun, Liza; Quinn, Michael; Xu, Heping; Stitt, Alan W.] Queens Univ Belfast, Ctr Med Expt, Belfast, Antrim, North Ireland.
   [Bierhaus, Angelika] Heidelberg Univ, Dept Med & Clin Chem, Heidelberg, Germany.
C3 Queens University Belfast; Ruprecht Karls University Heidelberg
RP Stitt, AW (通讯作者)，Queens Univ Belfast, Ctr Med Expt, Belfast, Antrim, North Ireland.
EM a.stitt@qub.ac.uk
RI Stitt, Alan/A-9842-2009; Ward, Micheal/G-1379-2012; Xu,
   Heping/A-4430-2008
OI Stitt, Alan/0000-0002-8647-9918; Ward, Micheal/0000-0001-8988-5797; Xu,
   Heping/0000-0003-4000-931X
FU Fight for Sight, Action Medical Research; Wolfson Royal Society; MRC
   [G0801962] Funding Source: UKRI; Medical Research Council [G0801962]
   Funding Source: researchfish; Fight for Sight [1871/72] Funding Source:
   researchfish
FX The authors acknowledge generous grant support from Fight for Sight,
   Action Medical Research. AWS holds a Wolfson Royal Society Merit Award.
   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 12
Z9 13
U1 1
U2 10
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 FEB 26
PY 2014
VL 9
IS 2
AR e89548
DI 10.1371/journal.pone.0089548
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AC3BC
UT WOS:000332389000058
PM 24586862
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Murakami, Y
   Matsumoto, H
   Roh, M
   Giani, A
   Kataoka, K
   Morizane, Y
   Kayama, M
   Thanos, A
   Nakatake, S
   Notomi, S
   Hisatomi, T
   Ikeda, Y
   Ishibashi, T
   Connor, KM
   Miller, JW
   Vavvas, DG
AF Murakami, Y.
   Matsumoto, H.
   Roh, M.
   Giani, A.
   Kataoka, K.
   Morizane, Y.
   Kayama, M.
   Thanos, A.
   Nakatake, S.
   Notomi, S.
   Hisatomi, T.
   Ikeda, Y.
   Ishibashi, T.
   Connor, K. M.
   Miller, J. W.
   Vavvas, D. G.
TI Programmed necrosis, not apoptosis, is a key mediator of cell loss and
   DAMP-mediated inflammation in dsRNA-induced retinal degeneration
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
DE retina; neuroprotection; necrosis; macula; degeneration
ID MOBILITY GROUP BOX-1; TOLL-LIKE RECEPTORS; MACULAR DEGENERATION;
   GEOGRAPHIC ATROPHY; PIGMENT-EPITHELIUM; TNF-ALPHA; 1 PROTEIN; DEATH;
   DETACHMENT; RELEASE
AB There is no known treatment for the dry form of an age-related macular degeneration (AMD). Cell death and inflammation are important biological processes thought to have central role in AMD. Here we show that receptor-interacting protein (RIP) kinase mediates necrosis and enhances inflammation in a mouse model of retinal degeneration induced by dsRNA, a component of drusen in AMD. In contrast to photoreceptor-induced apoptosis, subretinal injection of the dsRNA analog poly(I : C) caused necrosis of the retinal pigment epithelium (RPE), as well as macrophage infiltration into the outer retinas. In Rip3(-/-) mice, both necrosis and inflammation were prevented, providing substantial protection against poly(I : C)-induced retinal degeneration. Moreover, after poly(I : C) injection, Rip3(-/-) mice displayed decreased levels of pro-inflammatory cytokines (such as TNF-alpha and IL-6) in the retina, and attenuated intravitreal release of high-mobility group box-1 (HMGB1), a major damage-associated molecular pattern (DAMP). In vitro, poly(I : C)-induced necrosis were inhibited in Rip3-deficient RPE cells, which in turn suppressed HMGB1 release and dampened TNF-alpha and IL-6 induction evoked by necrotic supernatants. On the other hand, Rip3 deficiency did not modulate directly TNF-alpha and IL-6 production after poly(I : C) stimulation in RPE cells or macrophages. Therefore, programmed necrosis is crucial in dsRNA-induced retinal degeneration and may promote inflammation by regulating the release of intracellular DAMPs, suggesting novel therapeutic targets for diseases such as AMD.
C1 [Murakami, Y.; Matsumoto, H.; Roh, M.; Giani, A.; Kataoka, K.; Morizane, Y.; Kayama, M.; Thanos, A.; Connor, K. M.; Miller, J. W.; Vavvas, D. G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv,Angiogenesis Lab, Boston, MA 02114 USA.
   [Murakami, Y.; Nakatake, S.; Notomi, S.; Hisatomi, T.; Ikeda, Y.; Ishibashi, T.] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 812, Japan.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Kyushu University
RP Vavvas, DG (通讯作者)，Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv,Angiogenesis Lab, 243 Charles St, Boston, MA 02114 USA.
EM vavvas@meei.harvard.edu
RI Kataoka, Keiko/B-2806-2016; Giani, Andrea/L-5926-2017
OI Kataoka, Keiko/0000-0002-8795-6536; Giani, Andrea/0000-0003-0682-1945;
   Hisatomi, Toshio/0000-0003-2552-9595; Vavvas,
   Demetrios/0000-0002-8622-6478; Miller, Joan/0000-0003-2046-3996; Connor,
   Kip/0000-0002-2048-9080; Roh, Miin/0000-0003-3346-754X
FU Research to Prevent Blindness Physician Scientist Award; NIH [NEI
   R21EY023079-01A1, R01EY022084-01/S1]; Foundation Lions Eye Research
   Fund; Onassis Foundation; Yeatts Family Foundation; Rena Family
   Foundation; Bausch & Lomb Vitreoretinal Fellowship; NEI grant
   [EY014104]; Japanese Ministry of Education, Culture, Sports, Science,
   and Technology grant [25861637]; NATIONAL EYE INSTITUTE [R21EY023079,
   R01EY022084, P30EY014104] Funding Source: NIH RePORTER
FX We thank N Michaud (MEEI) and F Morikawa (Kyushu U) for technical
   assistance, and W Chao (MEEI) for her support in critical review. This
   work was supported by Research to Prevent Blindness Physician Scientist
   Award (DGV), NIH NEI R21EY023079-01A1 (DGV) Foundation Lions Eye
   Research Fund (DGV), Onassis Foundation (DGV), The Yeatts Family
   Foundation (JWM, DGV), Rena Family Foundation (JWM, DGV), Bausch & Lomb
   Vitreoretinal Fellowship (HM, Y Morizane and KM), NEI grant EY014104
   (MEEI Core Grant), NIH R01EY022084-01/S1 (KMC) and the Japanese Ministry
   of Education, Culture, Sports, Science, and Technology grant 25861637
   (Y. Murakami).
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NR 51
TC 132
Z9 138
U1 0
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
EI 1476-5403
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD FEB
PY 2014
VL 21
IS 2
BP 270
EP 277
DI 10.1038/cdd.2013.109
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA 290VY
UT WOS:000329787800012
PM 23954861
OA Green Published, Green Submitted, Bronze
DA 2022-11-30
ER

PT J
AU Liu, L
   Geng, J
   Wu, JY
   Yuan, Z
   Lian, J
   Desheng, H
   Chen, L
AF Liu, Lei
   Geng, Jin
   Wu, Jingyang
   Yuan, Zhe
   Lian, Jie
   Desheng, Huang
   Chen, Lei
TI Prevalence of ocular fundus pathology with type 2 diabetes in a Chinese
   urban community as assessed by telescreening
SO BMJ OPEN
LA English
DT Article
ID MACULAR DEGENERATION; RETINOPATHY; AGE; ASSOCIATION; MELLITUS; GLAUCOMA;
   RISK
AB Objective: To describe the telescreening model and assess the prevalence of ocular fundus pathology in patients with type 2 diabetes within a Chinese urban community.
   Design: Community-based cross-sectional study.
   Setting: Healthcare centre of Fengyutan Community, Shenyang, China.
   Participants: A total 528 patients (287 females) with type 2 diabetes mellitus (DM) were randomly recruited using health files from the healthcare centre of Fengyutan community between 8 October and 20 November 2012.
   Main outcome measures: Signs of any diabetic retinopathy (DR), signs of glaucoma and signs of age-related macular degeneration (AMD).
   Results: The main ocular fundus pathologies were DR (75 patients, 14.20%), 65 (86.67%) cases of which were newly detected, AMD (57 patients, 10.79%) and glaucoma (63 patients, 11.93%). The risk factors for fundus pathology were long duration of diabetes (OR 2.31, 95% CI 1.87 to 2.56), and higher fasting plasma glucose (OR 3.64, 95% CI 1.81 to 5.21) and glycated haemoglobin (HbA1c) levels (OR 3.83, 95% CI 1.87 to 6.35).
   Conclusions: There was a high prevalence of fundus pathology among patients with type 2 diabetes, and in most of the cases, this was newly detected. Community screening for fundus pathology among patients with a long duration of type 2 diabetes and high fasting plasma glucose and HbA1c levels using a telescreening model will provide an effective strategy for the prevention and treatment of fundus pathology.
C1 [Liu, Lei; Geng, Jin; Wu, Jingyang; Yuan, Zhe; Desheng, Huang; Chen, Lei] China Med Univ, Hosp 1, Dept Ophthalmol, Shenyang, Peoples R China.
   [Liu, Lei; Chen, Lei] China Med Univ, Hosp 1, Key Lab Endocrine Dis Liaoning Prov, Shenyang, Peoples R China.
   [Liu, Lei; Desheng, Huang] China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang, Peoples R China.
   [Lian, Jie] Healthcare Ctr Fengyutan Community, Shenyang, Peoples R China.
C3 China Medical University; China Medical University; China Medical
   University
RP Chen, L (通讯作者)，China Med Univ, Hosp 1, Dept Ophthalmol, Shenyang, Peoples R China.
EM carol1422@163.com
RI yuan, zhe/GYE-0922-2022
FU Liaoning Diabetic Eye Center; Liaoning Provincial Key Laboratory of
   Endocrine Diseases; Endocrine Institute of China Medical University
FX This study was supported by Liaoning Diabetic Eye Center and the
   Liaoning Provincial Key Laboratory of Endocrine Diseases, and the
   Endocrine Institute of China Medical University. The authors thank
   Fengping Shan, PhD, Professor of Immunology, China Medical University
   and Xiaomei Wu, Master of Medicine, Department of Clinical Epidemiology,
   First Affiliated Hospital of China Medical University.
CR Choi JK, 2011, ARCH OPHTHALMOL-CHIC, V129, P196, DOI 10.1001/archophthalmol.2010.355
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NR 17
TC 7
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
PY 2013
VL 3
IS 12
AR e004146
DI 10.1136/bmjopen-2013-004146
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 301OJ
UT WOS:000330541400075
PM 24381259
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hadziahmetovic, M
   Song, Y
   Wolkow, N
   Iacovelli, J
   Grieco, S
   Lee, J
   Lyubarsky, A
   Pratico, D
   Connelly, J
   Spino, M
   Harris, ZL
   Dunaief, JL
AF Hadziahmetovic, Majda
   Song, Ying
   Wolkow, Natalie
   Iacovelli, Jared
   Grieco, Steven
   Lee, Jennifer
   Lyubarsky, Arkady
   Pratico, Domenico
   Connelly, John
   Spino, Michael
   Harris, Z. Leah
   Dunaief, Joshua L.
TI The Oral Iron Chelator Deferiprone Protects against Iron
   Overload-Induced Retinal Degeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MACULAR DEGENERATION; OXIDATIVE STRESS; PIGMENT EPITHELIUM; BRUCHS
   MEMBRANE; DISEASE; DAMAGE; CERULOPLASMIN; INFLAMMATION; THALASSEMIA;
   THERAPY
AB PURPOSE. Iron-induced oxidative stress may exacerbate age-related macular degeneration (AMD). Ceruloplasmin/Hephaestin double-knockout (DKO) mice with age-dependent retinal iron accumulation and some features of AMD were used to test retinal protection by the oral iron chelator deferiprone (DFP).
   METHODS. Cultured retinal pigment epithelial (ARPE-19) cells and mice were treated with DFP. Transferrin receptor mRNA (Tfrc), an indicator of iron levels, was quantified by qPCR. In mice, retinal oxidative stress was assessed by mass spectrometry, and degeneration by histology and electroretinography.
   RESULTS. DFP at 60 mu M decreased labile iron in ARPE-19 cells, increasing Tfrc and protecting 70% of cells against a lethal dose of H2O2. DFP 1 mg/mL in drinking water increased retinal Tfrc mRNA 2.7-fold after 11 days and also increased transferrin receptor protein. In DKOs, DFP over 8 months decreased retinal iron levels to 72% of untreated mice, diminished retinal oxidative stress to 70% of the untreated level, and markedly ameliorated retinal degeneration. DFP was not retina toxic in wild-type (WT) or DKO mice, as assessed by histology and electroretinography.
   CONCLUSIONS. Oral DFP was not toxic to the mouse retina. It diminished retinal iron levels and oxidative stress and protected DKO mice against iron overload-induced retinal degeneration. Further testing of DFP for retinal disease involving oxidative stress is warranted. (Invest Ophthalmol Vis Sci. 2011;52:959-968) DOI:10.1167/iovs.10-6207
C1 [Hadziahmetovic, Majda; Song, Ying; Wolkow, Natalie; Iacovelli, Jared; Grieco, Steven; Lee, Jennifer; Lyubarsky, Arkady; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
   [Pratico, Domenico] Temple Univ, Dept Pharmacol, Philadelphia, PA 19122 USA.
   [Connelly, John; Spino, Michael] ApoPharma Inc, Toronto, ON, Canada.
   [Harris, Z. Leah] Vanderbilt Univ, Dept Pediat, Nashville, TN USA.
C3 University of Pennsylvania; Pennsylvania Medicine; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); Temple University;
   Vanderbilt University
RP Dunaief, JL (通讯作者)，305 Stellar Chance Labs, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@upenn.edu
RI Mohammed, Imran/J-8271-2012; Iacovelli, Jared/G-3668-2011; Pratico,
   Domenico/ABA-9590-2020
OI Mohammed, Imran/0000-0002-8412-0768; Harris, Zena
   Leah/0000-0003-0110-8438; Wolkow, Natalie/0000-0003-1524-115X
FU The American Health Assistance Foundation; Pennsylvania Lions Eye
   Research Foundation; ApoPharma; F. M. Kirby Foundation; Paul and Evanina
   Bell Mackall Foundation Trust; NATIONAL EYE INSTITUTE [R01EY015240,
   P30EY001583] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGING
   [F30AG037289] Funding Source: NIH RePORTER
FX Supported by The American Health Assistance Foundation, the Pennsylvania
   Lions Eye Research Foundation, ApoPharma, the F. M. Kirby Foundation,
   and the Paul and Evanina Bell Mackall Foundation Trust. The University
   of Pennsylvania and ApoPharma share intellectual property rights to the
   use of deferiprone for treatment of eye disease.
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NR 59
TC 79
Z9 86
U1 1
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 2011
VL 52
IS 2
BP 959
EP 968
DI 10.1167/iovs.10-6207
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 728AQ
UT WOS:000287846300045
PM 21051716
OA Green Published
DA 2022-11-30
ER

PT J
AU Xu, L
   You, QS
   Wang, YX
   Jonas, JB
AF Xu, Liang
   You, Qi Sheng
   Wang, Ya Xing
   Jonas, Jost B.
TI Associations between Gender, Ocular Parameters and Diseases: The Beijing
   Eye Study
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Gender; Intraocular pressure; Refractive error; Myopia; Hyperopia;
   Age-related macular degeneration; Open-angle glaucoma; Angle-closure
   glaucoma; Trachoma; Pterygium; Diabetic retinopathy; Beijing Eye Study
ID AGE-RELATED MACULOPATHY; RISK-FACTORS; DRY EYE; MACULAR DEGENERATION;
   ADULT-POPULATION; ANTERIOR-CHAMBER; POOLED FINDINGS; NORTHERN CHINA;
   PREVALENCE; URBAN
AB Background: To assess relationships between gender, ocular parameters and ocular diseases. Methods: The Beijing Eye Study is a population-based study including 4,439 Chinese. All participants underwent a detailed ophthalmic examination, anthropometric measurements and analytic blood examinations. Results: In multivariate regression analysis, female gender was significantly associated with a shallower anterior chamber (p < 0.001) and narrower anterior chamber angle (p = 0.001), higher prevalence of dry eye (p = 0.002), lower best-corrected visual acuity (p = 0.04) and lower presenting visual acuity (p = 0.046), and with the systemic parameters of lower educational level (p < 0.001), rural region (p = 0.002), lower frequency of smoking (p < 0.001) and alcohol consumption (p < 0.001), lower body height (p < 0.001), lower diastolic blood pressure (p < 0.001) and higher systolic blood pressure (p < 0.001), and higher serum concentrations of triglycerides (p = 0.005), low-density lipoproteins (p < 0.001) and high-density lipoproteins (p < 0.001). Men and women did not vary significantly in refractive error, intraocular pressure, central corneal thickness, size of the optic disk and parapapillary atrophy, and prevalences of retinal microvascular abnormalities, trachoma, pterygia, nuclear cataract, posterior subcapsular or cortical cataract, angle-closure glaucoma, open-angle glaucoma, age-related macular degeneration and retinal vein occlusions. Conclusions: After controlling for systemic factors, females have a shallower anterior chamber, a narrower anterior chamber angle and a higher prevalence of dry eye. Copyright (C) 2010 S. Karger AG, Basel
C1 [Xu, Liang; You, Qi Sheng; Wang, Ya Xing; Jonas, Jost B.] Capital Med Sci Univ, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing 100005, Peoples R China.
   [Jonas, Jost B.] Heidelberg Univ, Dept Ophthalmol, Fac Clin Med Mannheim, D-6800 Mannheim, Germany.
C3 Capital Medical University; Ruprecht Karls University Heidelberg
RP Xu, L (通讯作者)，Capital Med Sci 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; wang, YA
   XING/K-9671-2016
OI You, Qisheng/0000-0003-0743-7320; You, Qisheng/0000-0003-0743-7320;
   wang, YA XING/0000-0003-2749-7793
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NR 30
TC 13
Z9 13
U1 0
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 2011
VL 45
IS 4
BP 197
EP 203
DI 10.1159/000321522
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 758IF
UT WOS:000290157100006
PM 21079409
DA 2022-11-30
ER

PT J
AU Mozaffarieh, M
   Schotzau, A
   Josifova, T
   Flammer, J
AF Mozaffarieh, M.
   Schoetzau, A.
   Josifova, T.
   Flammer, Josef
TI The effect of ranibizumab versus photodynamic therapy on DNA damage in
   patients with exudative macular degeneration
SO MOLECULAR VISION
LA English
DT Article
ID SINGLET OXYGEN PRODUCTION; BASAL-CELL CARCINOMA; STRAND BREAKS;
   CIRCULATING LEUKOCYTES; VISUAL IMPAIRMENT; GLAUCOMA PATIENTS; OXIDATIVE
   DAMAGE; EPITHELIAL-CELLS; REPAIR; HYDROPEROXIDES
AB Purpose: To compare the effect of ranibizumab treatment versus photodynamic therapy (PDT) on single-stranded DNA damage in circulating leukocytes in patients with exudative age-related macular degeneration (AMD).
   Methods: A comparative quantification of single-stranded DNA breaks was performed in circulating leukocytes of AMD patients before and 30 min, 45 min, 60 min, and 24 h after two different modes of therapy: a) PDT; and b) intravitreal ranibizumab injection. DNA breaks lead to smaller pieces of DNA, which in an electrical field, migrate out of the nucleus forming a tail. Damage of an individual cell was quantified as a comet tail moment. The proportion of non-zero values compared to the total number of observations was referred to as "amount of DNA damage" expressed in arbitrary units (AU). Comparisons between time points and study groups were assessed using a linear mixed-effect model.
   Results: PDT induced an increase in the amount of single-stranded DNA damage in the circulating leukocytes from 0.2 AU (before treatment) to 0.53 AU (30 min after treatment). This increase was significant (p=0.004). In contrast, after ranibizumab treatment, the DNA damage in the circulating leukocytes remained unchanged.
   Conclusions: PDT purposely induces a local oxidative stress to damage the newly formed vessels. Our results indicate an additional systemic oxidative stress, apparent as amount of single-stranded DNA damage in the circulating leukocytes, for at least 30 min after treatment.
C1 [Mozaffarieh, M.; Schoetzau, A.; Josifova, T.; Flammer, Josef] Univ Basel Hosp, Dept Ophthalmol, Univ Eye Clin, CH-4031 Basel, Switzerland.
C3 University of Basel
RP Flammer, J (通讯作者)，Univ Basel Hosp, Dept Ophthalmol, Univ Eye Clin, Mittlere Str 91, CH-4031 Basel, Switzerland.
EM jflammer@uhbs.ch
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NR 41
TC 8
Z9 8
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 JUN 13
PY 2009
VL 15
IS 125-29
BP 1194
EP 1199
PG 6
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 470OS
UT WOS:000267985700003
PM 19536305
DA 2022-11-30
ER

PT J
AU Lavanya, R
   Wong, TY
   Aung, T
   Tan, DTH
   Saw, SM
   Tay, WT
   Wang, JJ
AF Lavanya, R.
   Wong, T. Y.
   Aung, T.
   Tan, D. T. H.
   Saw, S-M
   Tay, W. T.
   Wang, J. Jin
CA SiMES Team
TI Prevalence of cataract surgery and post-surgical visual outcomes in an
   urban Asian population: the Singapore Malay Eye Study
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID POSTERIOR SUBCAPSULAR CATARACTS; ANGLE-CLOSURE GLAUCOMA; RISK-FACTORS;
   LENS OPACITIES; CHINESE; BLINDNESS; ACUITY; IMPAIRMENT; DISEASES;
   INDIANS
AB Aim: The aim of the study was to describe the prevalence and visual outcomes of cataract surgery in an urban Asian population.
   Methods: This was a population-based study of 3280 Singapore Malays aged 40-80 years (response rate 78.7%). Participants had a standardised interview and comprehensive ocular examination. Poor post-operative visual outcome was defined as visual acuity <= 20/60 in operated eyes of unilateral cataract extractions or in the better-seeing eye of bilateral cataract extractions. Factors associated with poor visual outcome were assessed.
   Results: Of 3280 participants, 284 (men 52.3%) had unilateral cataract extractions (age-standardised prevalence 4.7%, 95% CI 4.2% to 5.4%) and 154 persons (54%) had bilateral extractions. Older age, male sex and the presence of diabetes were significant factors associated with having had cataract surgery. Poor visual outcomes were present in 10.8% of the operated eyes using best-corrected visual acuity. Diabetic retinopathy (25.5%), glaucoma (17%), age-related macular degeneration (14.9%) and posterior capsular opacification (14.9%) were the main causes of poor visual outcome after surgery. Under-corrected refractive error accounted for 60% of patients with post-operative presenting visual acuity of <= 20/60.
   Conclusions: Five per cent of the sample of the Malay population aged 40 - 80 years in Singapore had cataract surgery. One in ten had post-operative best-corrected visual acuity of 20/60 or worse, largely related to concomitant retinal diseases.
C1 [Lavanya, R.; Wong, T. Y.; Aung, T.; Tan, D. T. H.] Singapore Natl Eye Ctr, Singapore, Singapore.
   [Lavanya, R.; Wong, T. Y.; Aung, T.; Tan, D. T. H.; Saw, S-M; Tay, W. T.] Singapore Eye Res Inst, Singapore, Singapore.
   [Wong, T. Y.; Aung, T.; Tan, D. T. H.; Saw, S-M] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore.
   [Wong, T. Y.; Saw, S-M] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Community Occupat & Family Med, Singapore 117595, Singapore.
   [Wong, T. Y.; Wang, J. Jin] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.
   [Wang, J. Jin] Univ Sydney, Ctr Vis Res, Sydney, NSW 2006, Australia.
C3 Singapore National Eye Center; National University of Singapore;
   Singapore National Eye Center; National University of Singapore;
   National University of Singapore; Centre for Eye Research Australia;
   University of Melbourne; University of Sydney
RP Wang, JJ (通讯作者)，Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia.
EM jiejw@unimelb.edu
RI Wong, Tien Yin/AAC-9724-2020; Wang, Jie Jin/P-1499-2014; wang,
   jie/GRS-0942-2022
OI Wong, Tien Yin/0000-0002-8448-1264; Wang, Jie Jin/0000-0001-9491-4898; 
FU National Medical Research Council [0796/2003, 0863/2004, CSI/0002/2005];
   Biomedical Research Council [501/1/25-5]; Singapore Tissue Network
FX This study was supported by the National Medical Research Council Grants
   No 0796/2003, 0863/2004 and CSI/0002/2005, and Biomedical Research
   Council Grant No 501/1/25-5, with additional support from the Singapore
   Tissue Network and the Singapore Tissue Network.
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NR 27
TC 35
Z9 38
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 MAR
PY 2009
VL 93
IS 3
BP 299
EP 304
DI 10.1136/bjo.2008.148650
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 411NH
UT WOS:000263655800008
PM 18927226
DA 2022-11-30
ER

PT J
AU Marmorstein, LY
   McLaughlin, PJ
   Peachey, NS
   Sasaki, T
   Marmorstein, AD
AF Marmorstein, Lihua Y.
   McLaughlin, Precious J.
   Peachey, Neal S.
   Sasaki, Takako
   Marmorstein, Alan D.
TI Formation and progression of sub-retinal pigment epithelium deposits in
   Efemp1 mutation knock-in mice: a model for the early pathogenic course
   of macular degeneration
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID HONEYCOMB RETINAL DYSTROPHY; EXTRACELLULAR-MATRIX PROTEINS; BASAL
   LAMINAR DEPOSIT; HIGH-FAT DIET; CUTIS LAXA; ABERRANT ACCUMULATION;
   MALATTIA LEVENTINESE; PERINATAL LETHALITY; TISSUE LOCALIZATION;
   MOLECULAR-GENETICS
AB Malattia leventinese (ML) is a dominantly inherited macular degenerative disease characterized by the presence of sub-retinal pigment epithelium (RPE) deposits. With the exception of an earlier age of onset, ML patients exhibit symptoms and histopathology compatible with the diagnosis of age-related macular degeneration (AMD), the most common cause of incurable blindness. ML is caused by a mutation (R345W) in the gene EFEMP1 which encodes fibulin-3, a protein of unknown function. We generated a knock-in mouse carrying the disease-associated mutation in the murine Efemp1 gene. Small, isolated sub-RPE deposits developed as early as 4 months of age in both heterozygous and homozygous knock-in mice. Over time these deposits increased in size and number eventually becoming continuous sheets. In older mice membranous debris was observed within the deposits and within Bruch's membrane, and was accompanied by general RPE and choroidal abnormalities including degeneration, vacuolation, loss or disruption of the RPE basal infoldings, choroidal atrophy, and focal thickening of and invasion of cellular processes into Bruch's membrane. Fibulin-3 was found to accumulate in the sub-RPE deposits. Thus, the Efemp1 knockin mice reconstitute the most important histopathologic symptoms of both ML and AMD. We conclude that these mice are a valuable tool for studying the primary pathogenic course of basal deposits associated with macular degeneration and for testing prevention and treatment strategies for this class of diseases.
C1 Univ Arizona, Dept Ophthalmol & Visual Sci, Tucson, AZ 85711 USA.
   Univ Arizona, Dept Physiol, Tucson, AZ 85711 USA.
   Univ Arizona, Ctr Opt Sci, Tucson, AZ 85711 USA.
   Case Western Reserve Univ, Res Serv, Cleveland VA Med Ctr, Cleveland, OH 44106 USA.
   Case Western Reserve Univ, Cole Eye Inst, Cleveland Clin Fdn, Cleveland, OH 44106 USA.
   Case Western Reserve Univ, Dept Ophthalmol, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
   Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA.
C3 University of Arizona; University of Arizona; University of Arizona; US
   Department of Veterans Affairs; Veterans Health Administration (VHA);
   Case Western Reserve University; Louis Stokes Cleveland Veterans Affairs
   Medical Center; Case Western Reserve University; Cleveland Clinic
   Foundation; Case Western Reserve University; Cleveland Clinic
   Foundation; Oregon Health & Science University
RP Marmorstein, LY (通讯作者)，Univ Arizona, Dept Ophthalmol & Visual Sci, 655 N Alvernon Way,Suite 108, Tucson, AZ 85711 USA.
EM Lmarmorstein@eyes.arizona.edu
RI Peachey, Neal/G-5533-2010
OI Peachey, Neal/0000-0002-4419-7226
FU NATIONAL EYE INSTITUTE [R56EY013160, R01EY013847, R24EY015638,
   R01EY013160] Funding Source: NIH RePORTER; NEI NIH HHS [EY13847, R01
   EY013160, R24 EY015638, EY13160, R01 EY013847, R24EY15638] Funding
   Source: Medline
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NR 44
TC 82
Z9 84
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 15
PY 2007
VL 16
IS 20
BP 2423
EP 2432
DI 10.1093/hmg/ddm199
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 227SP
UT WOS:000250678400004
PM 17664227
OA Bronze
DA 2022-11-30
ER

PT J
AU Theodossiadis, PG
   Markomichelakis, NN
   Sfikakis, PP
AF Theodossiadis, Panagiotis G.
   Markomichelakis, Nikolaos N.
   Sfikakis, Petros P.
TI Tumor necrosis factor antagonists - Preliminary evidence for an emerging
   approach in the treatment of ocular inflammation
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Review
DE TNF; ophthalmology; EAU; infliximab; etanercept; uveitis; scleritis;
   retinitis; macular edema; ocular inflammation; safety
ID JUVENILE IDIOPATHIC ARTHRITIS; TNF-ALPHA THERAPY; EXPERIMENTAL
   AUTOIMMUNE UVEORETINITIS; PLACEBO-CONTROLLED TRIAL; PROLIFERATIVE
   DIABETIC-RETINOPATHY; REFRACTORY POSTERIOR UVEITIS; SIGHT THREATENING
   UVEITIS; RECEPTOR-DEFICIENT MICE; LONG-TERM TREATMENT; BEHCETS-DISEASE
AB The anti-tumor necrosis factor (TNF) monoclonal antibody infliximab and the soluble TNF receptor etanercept inhibit the pleiotropic actions of TNF and are widely used for the treatment of rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), spondylo-arthropathies (SpA), Crohn's disease, and psoriasis with an acceptable safety profile. A pathogenetic. role of TNF in ocular inflammatory conditions has recently emerged from small trials reporting preliminary results on the efficacy of these agents in patients with noninfectious uveitis, regardless of the origin of the disease. The authors review the published experience, derived mostly from investigator-sponsored trials and uncontrolled case series, on the use of TNF antagonists in approximately 280 patients with various ocular conditions who were inadequately controlled on currently available therapy. These reports suggest that TNF antagonists, mainly infliximab, which may have better efficacy than etanercept, are useful in the treatment of ocular inflammation associated with Adamantiades-Behret's disease, RA, JIA, SpA, Crohn's; sarcoidosis, and Graves' disease ophthalmopathy. Infliximab was also beneficial in small numbers of patients with idiopathic uveitis or scleritis, birdshot retinochoroiditis, uveitic and diabetic cystoid macular edema, and age-related macular degeneration. The currently available data are nonrandomized and thus preliminary, providing the foundation and justification for randomized trials to assess efficacy and safety. Until such results are available, knowledge regarding the use of anti-TNF regimens in ophthalmology is incomplete. However, the preliminary evidence points to a growing optimism for targeting TNF in patients with ocular inflammation.
C1 Univ Athens, Sch Med, Dept Ophthalmol 2, Laikon Hosp, GR-10679 Athens, Greece.
   Univ Athens, Sch Med, Dept Propedeut & Internal Med 1, Laikon Hosp, GR-10679 Athens, Greece.
C3 Athens Medical School; Laiko General Hospital; National & Kapodistrian
   University of Athens; Athens Medical School; Laiko General Hospital;
   National & Kapodistrian University of Athens
RP Theodossiadis, PG (通讯作者)，13 Lykiou St,Platia Rigilis 10675, Athens, Greece.
RI Sfikakis, Petros/AAD-7289-2019
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NR 158
TC 116
Z9 124
U1 0
U2 5
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-MAY
PY 2007
VL 27
IS 4
BP 399
EP 413
DI 10.1097/MAJ.0b013e3180318fbc
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 171AA
UT WOS:000246706100001
PM 17420690
DA 2022-11-30
ER

PT J
AU Fernandes, LHS
   Freund, KB
   Yannuzzi, LA
   Spaide, RF
   Huang, SJ
   Slakter, JS
   Sorenson, JA
AF Fernandes, LHS
   Freund, KB
   Yannuzzi, LA
   Spaide, RF
   Huang, SJ
   Slakter, JS
   Sorenson, JA
TI The nature of focal areas of hyperfluorescence or 'hot spots' imaged
   with indocyanine green angiography
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; PIGMENT EPITHELIAL DETACHMENTS;
   GUIDED LASER PHOTOCOAGULATION; CHORIORETINAL ANASTOMOSES; VASCULAR
   ANASTOMOSES; MACULAR DEGENERATION; VIDEOANGIOGRAPHY; NEOVASCULARIZATION;
   CLASSIFICATION; RETINA
AB Purpose: To clarify the frequency and nature of ICG angiographic "hot spots" seen in patients with neovascular age-related macular degeneration (ARMD).
   Methods: A consecutive series of newly diagnosed patients with neovascular ARMD and fluorescein angiographic evidence of occult choroidal neovascularization (occult CNV) was imaged with ICG angiography. Eyes with ICG angiographic "hot spots" were identified and further classified. A hot spot was defined as any area of abnormal hyperfluorescence, in the mid to late stages of ICG angiography, measuring less than 1 disk area in size.
   Results: From a total of 190 patients (220 eyes) with neovascular ARMD, 30 patients and 34 eyes (16%) with hot spots were identified. Hot spots were noted to be of three distinct patterns: polypoidal choroidal neovascularization (polypoidal CNV) in 21 of 34 eyes, or 62%; retinal angiomatous proliferation (RAP) in 11 of 34 eyes, or 30%; and focal occult CNV in 2 of 34 eyes, or 8%.
   Conclusions: A focal area of intense hyperfluorescence or so-called hot spot seen on ICG angiography in neovascular ARMD is due to one of three possible forms of neovascularization: most frequently polypoidal CNV, less commonly RAP, and infrequently nonspecific, focal occult CNV. Since neovascular ARMD may be caused by different types of neovascularization, each with distinct clinical manifestations, natural course, visual prognosis, and response to treatment, it is important to identify the precise nature of hot spots to establish an accurate diagnosis and, when appropriate, a specific form of management.
C1 Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA.
C3 Manhattan Eye Ear & Throat Hospital
RP Freund, KB (通讯作者)，Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, 210 E 64th St, New York, NY 10021 USA.
EM VRMNY@aol.com
RI Spaide, Richard/ABD-7368-2020; Freund, K. Bailey/V-7488-2018
OI Freund, K. Bailey/0000-0002-7888-9773
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NR 44
TC 52
Z9 55
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 2002
VL 22
IS 5
BP 557
EP 568
DI 10.1097/00006982-200210000-00005
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 604LC
UT WOS:000178621400005
PM 12441720
DA 2022-11-30
ER

PT J
AU Sheng, B
   Chen, XS
   Li, TY
   Ma, TX
   Yang, Y
   Bi, L
   Zhang, XY
AF Sheng, Bin
   Chen, Xiaosi
   Li, Tingyao
   Ma, Tianxing
   Yang, Yang
   Bi, Lei
   Zhang, Xinyuan
TI An overview of artificial intelligence in diabetic retinopathy and other
   ocular diseases
SO FRONTIERS IN PUBLIC HEALTH
LA English
DT Review
DE artificial intelligence; diabetic retinopathy; glaucoma; cataract;
   age-related macular degeneration
ID DEEP LEARNING-SYSTEM; MACULAR DEGENERATION; AUTOMATED DETECTION;
   PREDICTION; IMAGES; CLASSIFICATION; VALIDATION; GLAUCOMA; MODELS
AB Artificial intelligence (AI), also known as machine intelligence, is a branch of science that empowers machines using human intelligence. AI refers to the technology of rendering human intelligence through computer programs. From healthcare to the precise prevention, diagnosis, and management of diseases, AI is progressing rapidly in various interdisciplinary fields, including ophthalmology. Ophthalmology is at the forefront of AI in medicine because the diagnosis of ocular diseases heavy reliance on imaging. Recently, deep learning-based AI screening and prediction models have been applied to the most common visual impairment and blindness diseases, including glaucoma, cataract, age-related macular degeneration (ARMD), and diabetic retinopathy (DR). The success of AI in medicine is primarily attributed to the development of deep learning algorithms, which are computational models composed of multiple layers of simulated neurons. These models can learn the representations of data at multiple levels of abstraction. The Inception-v3 algorithm and transfer learning concept have been applied in DR and ARMD to reuse fundus image features learned from natural images (non-medical images) to train an AI system with a fraction of the commonly used training data (<1%). The trained AI system achieved performance comparable to that of human experts in classifying ARMD and diabetic macular edema on optical coherence tomography images. In this study, we highlight the fundamental concepts of AI and its application in these four major ocular diseases and further discuss the current challenges, as well as the prospects in ophthalmology.
C1 [Sheng, Bin; Li, Tingyao] Shanghai Jiao Tong Univ, Dept Comp Sci & Engn, Shanghai, Peoples R China.
   [Sheng, Bin; Chen, Xiaosi; Li, Tingyao; Yang, Yang; Zhang, Xinyuan] Beijing Tongren Hosp, Beijing Retinal & Choroidal Vasc Dis Study Grp, Beijing, Peoples R China.
   [Chen, Xiaosi; Yang, Yang; Zhang, Xinyuan] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing, Peoples R China.
   [Ma, Tianxing] Chongqing Univ, Univ Cincinnati Joint Coop Inst, Chongqing, Peoples R China.
   [Bi, Lei] Univ Sydney, Sch Comp Sci, Sydney, NSW, Australia.
C3 Shanghai Jiao Tong University; Capital Medical University; Chongqing
   University; University of Sydney
RP Sheng, B (通讯作者)，Shanghai Jiao Tong Univ, Dept Comp Sci & Engn, Shanghai, Peoples R China.; Sheng, B; Zhang, XY (通讯作者)，Beijing Tongren Hosp, Beijing Retinal & Choroidal Vasc Dis Study Grp, Beijing, Peoples R China.; Zhang, XY (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing, Peoples R China.
EM mmzxy2010@163.com; shengbin@sjtu.edu.cn
FU National Natural Science Foundation of China [81570850, 82070988,
   62272298]; Ministry of Science and Technology Foundation of China
   [2016YFC1305604]; Shanghai Municipal Science and Technology Major
   Project [2021SHZDZX0102]; College-level Project Fund of Shanghai Jiao
   tong University Affiliated Sixth People's Hospital [ynlc201909];
   Medical-industrial Cross-fund of Shanghai Jiao Tong University
   [YG2022QN089]
FX This work was supported by the National Natural Science Foundation of
   China (Grant 81570850, 82070988, and 62272298), the Ministry of Science
   and Technology Foundation of China (Grants 2016YFC1305604), the Shanghai
   Municipal Science and Technology Major Project under Grant (Grant
   2021SHZDZX0102), the College-level Project Fund of Shanghai Jiao tong
   University Affiliated Sixth People's Hospital (ynlc201909), and the
   Medical-industrial Cross-fund of Shanghai Jiao Tong University
   (YG2022QN089).
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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 2296-2565
J9 FRONT PUBLIC HEALTH
JI Front. Public Health
PD OCT 28
PY 2022
VL 10
AR 971943
DI 10.3389/fpubh.2022.971943
PG 15
WC Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Public, Environmental & Occupational Health
GA 6F2MR
UT WOS:000883902300001
PM 36388304
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Al-Ani, A
   Toms, D
   Sunba, S
   Giles, K
   Touahri, Y
   Schuurmans, C
   Ungrin, M
AF Al-Ani, Abdullah
   Toms, Derek
   Sunba, Saud
   Giles, Kayla
   Touahri, Yacine
   Schuurmans, Carol
   Ungrin, Mark
TI Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased
   Release of PEDF
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE RPE; microtissue; retina; tissue engineering; ESC-RPE; ARPE-19;
   ophthalmology
ID AGE-RELATED MACULOPATHY; PLURIPOTENT STEM-CELLS; MACULAR DEGENERATION;
   INTERPHOTORECEPTOR MATRIX; VISUAL IMPAIRMENT; GENE-THERAPY; IN-VITRO;
   RPE; GROWTH; EXPRESSION
AB The retinal pigmented epithelium (RPE) plays a critical role in photoreceptor survival and function. RPE deficits are implicated in a wide range of diseases that result in vision loss, including age-related macular degeneration (AMD) and Stargardt disease, affecting millions worldwide. Subretinal delivery of RPE cells is considered a promising avenue for treatment, and encouraging results from animal trials have supported recent progression into the clinic. However, the limited survival and engraftment of transplanted RPE cells delivered as a suspension continues to be a major challenge. While RPE delivery as epithelial sheets exhibits improved outcomes, this comes at the price of increased complexity at both the production and transplant stages. In order to combine the benefits of both approaches, we have developed size-controlled, scaffold-free RPE microtissues (RPE-mu Ts) that are suitable for scalable production and delivery via injection. RPE-mu Ts retain key RPE molecular markers, and interestingly, in comparison to conventional monolayer cultures, they show significant increases in the transcription and secretion of pigment-epithelium-derived factor (PEDF), which is a key trophic factor known to enhance the survival and function of photoreceptors. Furthermore, these microtissues readily spread in vitro on a substrate analogous to Bruch's membrane, suggesting that RPE-mu Ts may collapse into a sheet upon transplantation. We anticipate that this approach may provide an alternative cell delivery system to improve the survival and integration of RPE transplants, while also retaining the benefits of low complexity in production and delivery.
C1 [Al-Ani, Abdullah; Toms, Derek; Sunba, Saud; Giles, Kayla; Ungrin, Mark] Univ Calgary, Dept Comparat Biol & Expt Med, Fac Vet Med, Calgary, AB T2N 1N4, Canada.
   [Al-Ani, Abdullah; Toms, Derek; Sunba, Saud; Ungrin, Mark] Univ Calgary, Alberta Childrens Hosp, Res Inst, Calgary, AB T2N 4N1, Canada.
   [Al-Ani, Abdullah; Ungrin, Mark] Univ Alberta, Alberta Diabet Inst, Edmonton, AB T6G 2E1, Canada.
   [Al-Ani, Abdullah; Ungrin, Mark] Univ Calgary, Biomed Engn Grad Program, Calgary, AB T2N 1N4, Canada.
   [Al-Ani, Abdullah] Univ Calgary, Cumming Sch Med, Calgary, AB T2N 4N1, Canada.
   [Touahri, Yacine; Schuurmans, Carol] Sunnybrook Res Inst, Toronto, ON M4N 3M5, Canada.
   [Touahri, Yacine; Schuurmans, Carol] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
C3 University of Calgary; Alberta Childrens Hospital; University of
   Calgary; University of Alberta; University of Calgary; University of
   Calgary; University of Toronto; Sunnybrook Research Institute;
   University Toronto Affiliates; Sunnybrook Health Science Center;
   University of Toronto
RP Toms, D; Ungrin, M (通讯作者)，Univ Calgary, Dept Comparat Biol & Expt Med, Fac Vet Med, Calgary, AB T2N 1N4, Canada.; Toms, D; Ungrin, M (通讯作者)，Univ Calgary, Alberta Childrens Hosp, Res Inst, Calgary, AB T2N 4N1, Canada.; Ungrin, M (通讯作者)，Univ Alberta, Alberta Diabet Inst, Edmonton, AB T6G 2E1, Canada.; Ungrin, M (通讯作者)，Univ Calgary, Biomed Engn Grad Program, Calgary, AB T2N 1N4, Canada.
EM saud.sunba@ucalgary.ca; yacine.touahri@sunnybrook.ca;
   carol.schuurmans@sunnybrook.ca
OI Schuurmans, Carol/0000-0003-3567-0058; Al-Ani,
   Abdullah/0000-0001-5057-7033; Ungrin, Mark/0000-0002-7410-1491; Toms,
   Derek/0000-0002-5114-7147
FU Brain Canada; Canadian Institutes of Health Research; University of
   Calgary Biomedical Engineering Graduate Program; Alberta Children's
   Hospital Research Institute
FX This research was funded by Brain Canada (C.S. and M.U.). A.A.-A.
   received funding from the Canadian Institutes of Health Research and the
   University of Calgary Biomedical Engineering Graduate Program. Both
   A.A.-A. and D.T. were supported by fellowships from the Alberta
   Children's Hospital Research Institute.
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NR 101
TC 1
Z9 1
U1 0
U2 1
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 NOV
PY 2021
VL 22
IS 21
AR 11317
DI 10.3390/ijms222111317
PG 19
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA WX3LQ
UT WOS:000718502000001
PM 34768747
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Ohishi, K
   Hosono, K
   Obana, A
   Noda, A
   Hiramitsu, T
   Hotta, Y
   Minoshima, S
AF Ohishi, Kentaro
   Hosono, Katsuhiro
   Obana, Akira
   Noda, Akio
   Hiramitsu, Tadahisa
   Hotta, Yoshihiro
   Minoshima, Shinsei
TI Identification of susceptibility loci for light-induced visual
   impairment in rats
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Backcross; Morris water maze; Retinal photic injury; Strain difference;
   Susceptibility loci
ID MACULAR DEGENERATION; DAMAGE SUSCEPTIBILITY; GENETIC-FACTORS; AGE;
   RHODOPSIN; RPE65; PERFORMANCE; MUTATIONS; PROGRESS; STRAINS
AB Bright light exposure in animals results in the selective degeneration of the outer retina, known as "retinal photic injury" (RPI). The susceptibility to RPI differs among rat strains. WKY rats display susceptibility to RPI with extensive retinal degeneration observed in the sagittal eye specimen, whereas LEW strain rats are resistant to it, showing only slight or no degeneration. In the present study, we first established an ethological screening method using the Morris water maze to discern differential susceptibility among the living rats. WKY and LEW were crossed to produce the first filial generation (F-1) offspring. Maze-trained individuals were exposed to bright, white light. The screening test results demonstrated that the susceptibility to light-induced visual impairment in rats is a dominant Mendelian susceptibility trait, as F-1 rats were susceptible to visual impairment like WKY rats. Therefore, F-1 rats were backcrossed with recessive LEW to produce the first backcross offspring (BC1). Subsequent recurrent backcrossing while selecting for the susceptibility, indicated a segregation ratio of ca. 24% in BC1 and BC2 generations, indicating the involvement of two or more genes in the susceptibility. Further, microsatellite analysis of BC1-to-BC4 individuals using microsatellite markers mapped two susceptibility loci on chromosome segments 5q36 and 19q11-q12, named RPI susceptibility (Rpi)1 and Rpi2, respectively. This study provides an insight into mechanisms underlying differential susceptibility, which could help decipher the mechanism underlying the onset/progression of human age-related macular degeneration.
C1 [Ohishi, Kentaro; Minoshima, Shinsei] Hamamatsu Univ Sch Med, Preeminent Med Photon Educ & Res Ctr, Inst Med Photon Res, Higashi Ku,Dept Photomed Genom, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan.
   [Hosono, Katsuhiro; Hotta, Yoshihiro] Hamamatsu Univ Sch Med, Dept Ophthalmol, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan.
   [Obana, Akira] Hamamatsu Univ Sch Med, Preeminent Med Photon Educ & Res Ctr, Hamamatsu BioPhoton Innovat Chair,Inst Med Photon, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan.
   [Obana, Akira] Seirei Hamamatsu Gen Hosp, Dept Ophthalmol, Naka Ku, 2-12-12 Sumiyoshi, Hamamatsu, Shizuoka 4308558, Japan.
   [Noda, Akio] Hamamatsu Univ Sch Med, Dept Integrated Human Sci Math, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan.
   [Hiramitsu, Tadahisa] Hamamatsu Univ Sch Med, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan.
C3 Hamamatsu University School of Medicine; Hamamatsu University School of
   Medicine; Hamamatsu University School of Medicine; Hamamatsu University
   School of Medicine; Hamamatsu University School of Medicine
RP Ohishi, K (通讯作者)，Hamamatsu Univ Sch Med, Preeminent Med Photon Educ & Res Ctr, Inst Med Photon Res, Higashi Ku,Dept Photomed Genom, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan.
EM kohishi@hama-med.ac.jp
FU JSPS KAKENHI [18791270, 18K09401]; MEXT KAKENHI [17019027]
FX This work was supported by JSPS KAKENHI Grant Number 18791270 and
   18K09401, by MEXT KAKENHI Grant Number 17019027. We thank the Advanced
   Research Facilities & Services and Laboratory Animal Facilities &
   Services members in the Preeminent Medical Photonics Education &
   Research Center for supporting this work. We would like to thank Editage
   (www.editage.jp) for English language editing.
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NR 49
TC 0
Z9 0
U1 1
U2 1
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 2021
VL 210
AR 108688
DI 10.1016/j.exer.2021.108688
EA JUL 2021
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UO7XI
UT WOS:000694905500006
PM 34237304
DA 2022-11-30
ER

PT J
AU Chea, N
   Nam, Y
AF Chea, Nakhim
   Nam, Yunyoung
TI Classification of Fundus Images Based on Deep Learning for Detecting Eye
   Diseases
SO CMC-COMPUTERS MATERIALS & CONTINUA
LA English
DT Article
DE Multi-categorical classification; deep neural networks; glaucoma;
   age-related macular degeneration; diabetic retinopathy
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; DIABETIC-RETINOPATHY;
   GLOBAL PREVALENCE; NEURAL-NETWORK; BLOOD-VESSELS; IDENTIFICATION;
   ENHANCEMENT; WISCONSIN; DIAGNOSIS
AB Various techniques to diagnose eye diseases such as diabetic retinopathy (DR), glaucoma (GLC), and age-related macular degeneration (AMD), are possible through deep learning algorithms. A few recent studies have examined a couple of major diseases and compared them with data from healthy subjects. However, multiple major eye diseases, such as DR, GLC, and AMD, could not be detected simultaneously by computer-aided systems to date. There were just high-performance-outcome researches on a pair of healthy and eye-diseased group, besides of four categories of fundus image classification. To have a better knowledge of multi-categorical classification of fundus photographs, we used optimal residual deep neural networks and effective image preprocessing techniques, such as shrinking the region of interest, iso-luminance plane contrast-limited adaptive histogram equalization, and data augmentation. Applying these to the classification of three eye diseases from currently available public datasets, we achieved peak and average accuracies of 91.16% and 85.79%, respectively. The specificities for images from the eyes of healthy, GLC, AMD, and DR patients were 90.06%, 99.63%, 99.82%, and 91.90%, respectively. The better specificity performances may alert patient in an early stage of eye diseases to prevent vision loss. This study presents a possible occurrence of a multi-categorical deep neural network technique that can be deemed as a successful pilot study of classification for the three most-common eye diseases and can be used for future assistive devices in computer-aided clinical applications.
C1 [Chea, Nakhim] Soonchunhyang Univ, Dept ICT Convergence Rehabil Engn, Asan 31538, South Korea.
   [Nam, Yunyoung] Soonchunhyang Univ, Dept Comp Sci & Engn, Asan 31538, South Korea.
C3 Soonchunhyang University; Soonchunhyang University
RP Nam, Y (通讯作者)，Soonchunhyang Univ, Dept Comp Sci & Engn, Asan 31538, South Korea.
EM ynam@sch.ac.kr
FU KIAT (Korea Institute for Advancement of Technology) - Korea Government
   (MOTIE: Ministry of Trade Industry and Energy) [P0012724]; Soonchunhyang
   University Research Fund
FX This work was supported by the KIAT (Korea Institute for Advancement of
   Technology) grant funded by the Korea Government (MOTIE: Ministry of
   Trade Industry and Energy) (No. P0012724) and the Soonchunhyang
   University Research Fund.
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NR 55
TC 5
Z9 6
U1 1
U2 6
PU TECH SCIENCE PRESS
PI HENDERSON
PA 871 CORONADO CENTER DR, SUTE 200, HENDERSON, NV 89052 USA
SN 1546-2218
EI 1546-2226
J9 CMC-COMPUT MATER CON
JI CMC-Comput. Mat. Contin.
PY 2021
VL 67
IS 1
BP 411
EP 426
DI 10.32604/cmc.2021.013390
PG 16
WC Computer Science, Information Systems; Materials Science,
   Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Materials Science
GA PT3EC
UT WOS:000608499100023
OA gold
DA 2022-11-30
ER

PT J
AU Sun, T
   Wei, Y
   Chen, W
   Ding, Y
AF Sun, Tao
   Wei, Yue
   Chen, Wei
   Ding, Ying
TI Genome-wide association study-based deep learning for survival
   prediction
SO STATISTICS IN MEDICINE
LA English
DT Article
DE AMD progression; deep learning; GWAS; predictor importance; survival
   prediction
ID RISK; PROGRESSION; SELECTION; NETWORKS; DISEASE; MODELS; SCORE
AB Informative and accurate survival prediction with individualized dynamic risk profiles over time is critical for personalized disease prevention and clinical management. The massive genetic data, such as SNPs from genome-wide association studies (GWAS), together with well-characterized time-to-event phenotypes provide unprecedented opportunities for developing effective survival prediction models. Recent advances in deep learning have made extraordinary achievements in establishing powerful prediction models in the biomedical field. However, the applications of deep learning approaches in survival prediction are limited, especially with utilizing the wealthy GWAS data. Motivated by developing powerful prediction models for the progression of an eye disease, age-related macular degeneration (AMD), we develop and implement a multilayer deep neural network (DNN) survival model to effectively extract features and make accurate and interpretable predictions. Various simulation studies are performed to compare the prediction performance of the DNN survival model with several other machine learning-based survival models. Finally, using the GWAS data from two large-scale randomized clinical trials in AMD with over 7800 observations, we show that the DNN survival model not only outperforms several existing survival prediction models in terms of prediction accuracy (eg, c-index=0.76), but also successfully detects clinically meaningful risk subgroups by effectively learning the complex structures among genetic variants. Moreover, we obtain a subject-specific importance measure for each predictor from the DNN survival model, which provides valuable insights into the personalized early prevention and clinical management for this disease.
C1 [Sun, Tao; Wei, Yue; Chen, Wei; Ding, Ying] Univ Pittsburgh, Dept Biostat, 130 Soto St, Pittsburgh, PA 15261 USA.
   [Sun, Tao] Renmin Univ China, Ctr Appl Stat, Beijing, Peoples R China.
   [Sun, Tao] Renmin Univ China, Sch Stat, Beijing, Peoples R China.
   [Chen, Wei] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; Renmin University of China; Renmin University of China;
   Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh
RP Ding, Y (通讯作者)，Univ Pittsburgh, Dept Biostat, 130 Soto St, Pittsburgh, PA 15261 USA.
EM yingding@pitt.edu
FU National Institutes of Health [UL1TR001857]
FX We thank the participants in the AREDS and AREDS2 studies and the
   International AMD Genomics Consortium for generating the genetic data
   and performing the quality check. This project was supported by the
   National Institutes of Health through Grant Number UL1TR001857.
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TC 11
Z9 11
U1 3
U2 22
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD DEC 30
PY 2020
VL 39
IS 30
BP 4605
EP 4620
DI 10.1002/sim.8743
EA SEP 2020
PG 16
WC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Medicine, Research &
   Experimental; Statistics & Probability
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Research & Experimental
   Medicine; Mathematics
GA PE8LO
UT WOS:000572375800001
PM 32974946
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Simon, MV
   Spalm, FHP
   Vera, MS
   Rotstein, NP
AF Victoria Simon, M.
   Prado Spalm, Facundo H.
   Vera, Marcela S.
   Rotstein, Nora P.
TI Sphingolipids as Emerging Mediators in Retina Degeneration
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Review
DE ceramide; sphingosine-1-phosphate; sphingosine; ceramide-1-phosphate;
   photoreceptor; glia; pigmented epithelium
ID PIGMENT EPITHELIAL-CELLS; SPHINGOSINE KINASE 1; GROWTH-FACTOR-BETA;
   LIPID PHOSPHATE PHOSPHATASES; STRESS-INDUCED APOPTOSIS; 1-PHOSPHATE
   RECEPTOR 1; CERAMIDE SYNTHASE 2; ACID SPHINGOMYELINASE; OPTIC-NERVE;
   DNA-SYNTHESIS
AB The sphingolipids ceramide (Cer), sphingosine-1-phosphate (S1P), sphingosine (Sph), and ceramide-1-phosphate (C1P) are key signaling molecules that regulate major cellular functions. Their roles in the retina have gained increasing attention during the last decade since they emerge as mediators of proliferation, survival, migration, neovascularization, inflammation and death in retina cells. As exacerbation of these processes is central to retina degenerative diseases, they appear as crucial players in their progression. This review analyzes the functions of these sphingolipids in retina cell types and their possible pathological roles. Cer appears as a key arbitrator in diverse retinal pathologies; it promotes inflammation in endothelial and retina pigment epithelium (RPE) cells and its increase is a common feature in photoreceptor death in vitro and in animal models of retina degeneration; noteworthy, inhibiting Cer synthesis preserves photoreceptor viability and functionality. In turn, S1P acts as a double edge sword in the retina. It is essential for retina development, promoting the survival of photoreceptors and ganglion cells and regulating proliferation and differentiation of photoreceptor progenitors. However, S1P has also deleterious effects, stimulating migration of Muller glial cells, angiogenesis and fibrosis, contributing to the inflammatory scenario of proliferative retinopathies and age related macular degeneration (AMD). C1P, as S1P, promotes photoreceptor survival and differentiation. Collectively, the expanding role for these sphingolipids in the regulation of critical processes in retina cell types and in their dysregulation in retina degenerations makes them attractive targets for treating these diseases.
C1 [Victoria Simon, M.; Prado Spalm, Facundo H.; Vera, Marcela S.; Rotstein, Nora P.] Univ Nacl Sur, Dept Biol Bioquim & Farm, Inst Invest Bioquim Bahia Blanca INIBIBB, Argentine Natl Res Council CONICET, Bahia Blanca, Buenos Aires, Argentina.
C3 National University of the South
RP Rotstein, NP (通讯作者)，Univ Nacl Sur, Dept Biol Bioquim & Farm, Inst Invest Bioquim Bahia Blanca INIBIBB, Argentine Natl Res Council CONICET, Bahia Blanca, Buenos Aires, Argentina.
EM inrotste@criba.edu.ar
FU National Agency for Science and Technology (ANPCYT) [PICT-2015-0284];
   National Research Council of Argentina (CONICET) [PIP 11220-1101-00827];
   Universidad Nacional del Sur [PGI 24/B254]
FX Funding from the National Agency for Science and Technology (ANPCYT)
   (PICT-2015-0284 to NR); National Research Council of Argentina (CONICET)
   (PIP 11220-1101-00827, to NR); and PGI 24/B254 from the Secretary of
   Science and Technology, Universidad Nacional del Sur (to NR).
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NR 290
TC 36
Z9 36
U1 5
U2 8
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD JUN 11
PY 2019
VL 13
AR 246
DI 10.3389/fncel.2019.00246
PG 25
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA ID3SI
UT WOS:000471597000001
PM 31244608
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ooe, E
   Tsuruma, K
   Kuse, Y
   Kobayashi, S
   Shimazawa, M
   Hara, H
AF Ooe, Emi
   Tsuruma, Kazuhiro
   Kuse, Yoshiki
   Kobayashi, Saori
   Shimazawa, Masamitsu
   Hara, Hideaki
TI The involvement of ATF4 and S-opsin in retinal photoreceptor cell damage
   induced by blue LED light
SO MOLECULAR VISION
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; DEGENERATION;
   TRANSLATION; DEATH
AB Purpose: Blue light is a high-energy emitting light with a short wavelength in the visible light spectrum. Blue light induces photoreceptor apoptosis and causes age-related macular degeneration or retinitis pigmentosa. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress induced by blue light-emitting diode (LED) light exposure in murine photoreceptor cells.
   Methods: The murine photoreceptor cell line was incubated and exposed to blue LED light (464 nm blue LED light, 450 lx, 3 to 24 h). The expression of the factors involved in the unfolded protein response pathway was examined using quantitative real-time reverse transcription (RT)-PCR and immunoblot analysis. The aggregation of short-wavelength opsin (S-opsin) in the murine photoreceptor cells was observed with immunostaining. The effect of S-opsin knockdown on ATF4 expression in the murine photoreceptor cell line was also investigated.
   Results: Exposure to blue LED light increased the bip, atf4, and grp94 mRNA levels, induced the expression of ATF4 protein, and increased the levels of ubiquitinated proteins. Exposure to blue LED light in combination with ER stress inducers (tunicamycin and dithiothreitol) induced the aggregation of S-opsin. S-opsin mRNA knockdown prevented the induction of ATF4 expression in response to exposure to blue LED light.
   Conclusions: These findings indicate that the aggregation of S-opsin induced by exposure to blue LED light causes ER stress, and ATF4 activation in particular.
C1 [Ooe, Emi; Tsuruma, Kazuhiro; Kuse, Yoshiki; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigakunishi, Daigakunishi, Gifu 5011196, Japan.
   [Ooe, Emi; Kobayashi, Saori] Wakasa Seikatsu Co Ltd, Shimogyo Ku, 22 Naginataboko Cho, Kyoto, Japan.
C3 Gifu Pharmaceutical University
RP Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigakunishi, Daigakunishi, Gifu 5011196, Japan.
EM hidehara@gifu-pu.ac.jp
RI Kobayashi, Saori/GXV-3835-2022; Kuse, Yoshiki/AAB-7445-2021
OI Hara, Hideaki/0000-0003-2046-9001
FU Wakasa Seikatsu Co. Ltd.
FX The authors thank all the participants in this study, without whom the
   research could not have been performed. This work was performed with
   support from Wakasa Seikatsu Co. Ltd.
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NR 24
TC 9
Z9 9
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 5
PY 2017
VL 23
BP 52
EP 59
PG 8
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA EQ4FQ
UT WOS:000398031000001
PM 28331281
DA 2022-11-30
ER

PT J
AU Varzaru, I
   Untea, AE
   Van, I
AF Varzaru, Iulia
   Untea, Arabela Elena
   Van, Ilie
TI Determination of bioactive compounds with benefic potential on health in
   several medicinal plants
SO ROMANIAN BIOTECHNOLOGICAL LETTERS
LA English
DT Article
DE lutein and zeaxanthin; vitamin E; zinc; medicinal plants; eye diseases
ID SPECTROSCOPY; CAROTENOIDS; EXTRACTION; DIGESTION; LUTEIN
AB Several bioactive compounds from plants like Chelidonium majus, Equisetum arvense and Hypericum perforatum are well known for their potential benefic effects on human and animal health. However, few data on the effect of these plants on various ocular diseases, such as age-related macular degeneration (AMD), cataracts, glaucoma have been reported. The purpose of this study was to investigate the content of several bioactive compounds (lutein and zeaxanthin, vitamin E and zinc) from twelve medicinal plants, known for their antioxidant activity. Four of these herbs are known for their pharmacological effects in inflammatory eye disorders, and the rest of them are plants with yellow flowers recommended in treatments of other diseases like cardiovascular, liver, skin, nervous disorders.
   The plants characterization regarding the lutein and zeaxanthin content was performed by developing and validating a HPLC method. The processing of the results was done using the Multi-Criteria Decision Analysis (MDCA) in order to make choices taking into account multiple criteria simultaneously. The results of the study showed that Calendula officinalis, Chelidonium majus, Equisetum arvense and Hypericum perforatum were the plants with the four highest total ranking scores, the last three of them not being used in treating eye disorders. Calendula officinalis had 5.239 +/- 0.19 mg/100 g lutein and zeaxanthin, 168.68 +/- 5.06 mu g/mL vitamin E and 32.13 +/- 0.73 mu g/mL Zn.
   These results provide scientific support for using these plants in the treatment of eye disorders.
C1 [Varzaru, Iulia; Van, Ilie] Univ Agron Sci & Vet Med, Bucharest, Romania.
   [Untea, Arabela Elena] Natl Res Dev Inst Anim Biol & Nutr IBNA, Balotesti, Romania.
C3 University of Agronomic Science & Veterinary Medicine - Bucharest
RP Varzaru, I (通讯作者)，Univ Agron Sci & Vet Med, Bucharest, Romania.
EM iulia_maros@yahoo.com
RI Varzaru, Iulia/AAI-5901-2020; Untea, A.E./ABG-6131-2020
FU European Social Found, Human Resources Development Programme
   [POSDRU/159/1.5/S/132765]
FX This paper was published under the frame of European Social Found, Human
   Resources Development Programme 2007-2013, project no.
   POSDRU/159/1.5/S/132765.
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NR 39
TC 10
Z9 10
U1 1
U2 18
PU ARS DOCENDI
PI BUCHAREST
PA SOS PANDURI 90, SECT 5, BUCHAREST, RO-050663, ROMANIA
SN 1224-5984
J9 ROM BIOTECH LETT
JI Rom. Biotech. Lett.
PD SEP-OCT
PY 2015
VL 20
IS 5
BP 10773
EP 10783
PG 11
WC Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology
GA CX0SA
UT WOS:000365405800005
DA 2022-11-30
ER

PT J
AU Kuehlewein, L
   Sadda, SR
   Sarraf, D
AF Kuehlewein, L.
   Sadda, S. R.
   Sarraf, D.
TI OCT angiography and sequential quantitative analysis of type 2
   neovascularization after ranibizumab therapy
SO EYE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; CHOROIDAL NEOVASCULARIZATION; MACULAR
   DEGENERATION; MOTION CORRECTION
AB Purpose To study the precise structural aspects of a type 2 neovascular membrane in a patient with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography and perform sequential quantitative analysis of the membrane after ranibizumab therapy.
   Patients and methods Split-spectrum amplitude-decorrelation (SSADA) OCT angiography macular cubes (3x3 mm) were acquired with a light source centered at 840 nm, a bandwidth of 45 nm, and an A-scan-rate of 70 000 scans per second. Visible pathologic vessels were outlined manually on average intensity projection en face images, and the area of the lesion and the vessel density were measured at baseline and follow-up.
   Results At baseline, the neovascular lesion measured 4.12 mm(2) and the vessel density was 19.83 mm(-1). Four weeks after the first, and 2 and 4 weeks after the second ranibizumab injection, OCT angiography revealed a progressively smaller vascular lesion (2.32, 1.77 and 1.64 mm(2)), and vessel density (10.24, 8.52 and 7.57 mm(-1)), although the large central trunks of the lesion were unchanged.
   Conclusions In this study, an obvious reduction in size and vessel density of the neovascular lesion was noted after treatment with ranibizumab using SSADA OCT angiography technology. Microvascular components can be delineated with precision, suggesting that this technique may be useful for the management of patients with neovascular AMD in a clinical setting as well as for future clinical trials.
C1 [Kuehlewein, L.; Sadda, S. R.] Doheny Eye Inst, Los Angeles, CA 90033 USA.
   [Kuehlewein, L.; Sadda, S. R.; Sarraf, D.] Stein Eye Inst, Los Angeles, CA USA.
   [Sarraf, D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Sarraf, D.] Greater Los Angeles VA Healthcare Ctr, Los Angeles, 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; US Department of
   Veterans Affairs; Veterans Health Administration (VHA); VA Greater Los
   Angeles Healthcare System
RP Sarraf, D (通讯作者)，Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA.
EM dsarraf@ucla.edu
FU Carl Zeiss Meditec; Optos; Allergan
FX Dr Sadda is a co-inventor of Doheny intellectual property related to
   optical coherence tomography that has been licensed by Topcon Medical
   Systems and is a member of the scientific advisory board for Heidelberg
   Engineering. Dr Sadda receives research support from and serves as a
   consultant for Carl Zeiss Meditec, Optos, and Allergan. He also serves
   as a consultant for Alcon, Novartis, and Iconic.
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NR 10
TC 104
Z9 108
U1 0
U2 9
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 2015
VL 29
IS 7
BP 932
EP 935
DI 10.1038/eye.2015.80
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CM5LC
UT WOS:000357728300014
PM 25976641
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Blaha, GR
   Brooks, NO
   Mackel, CE
   Pani, A
   Stewart, AP
   Price, LL
   Barouch, FC
   Chang, J
   Marx, JL
AF Blaha, Gregory R.
   Brooks, Nneka O.
   Mackel, Charles E.
   Pani, Altin
   Stewart, Avon P.
   Price, Lori L.
   Barouch, Fina C.
   Chang, Jeffrey
   Marx, Jeffrey L.
TI CHANGES IN FLARE AFTER INTRAVITREAL INJECTION OF THREE DIFFERENT
   ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR MEDICATIONS
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE aflibercept; anti-VEGF; Avastin; bevacizumab; endophthalmitis; Eylea;
   flare; inflammation; Lucentis; ranibizumab
ID BEVACIZUMAB
AB Purpose: To compare the change in anterior chamber flare after intravitreal injection of the anti-vascular endothelial growth factor agents bevacizumab, aflibercept, and ranibizumab.
   Methods: Sixty-one eyes of 53 patients underwent intravitreal injection with antivascular endothelial growth factor medications for exudative age-related macular degeneration, diabetic macular edema, or retinal vein occlusion. There were a total of 26 eyes injected with bevacizumab, 14 eyes injected with aflibercept, and 21 eyes injected with ranibizumab. Anterior segment flare was measured with a laser flare meter (Kowa) before intravitreal injection and 1 day after injection. The change in flare was analyzed.
   Results: The mean change in flare after 1 day was +2.5 photons per millisecond in patients who received bevacizumab, 0.0 photons per millisecond for aflibercept, and -0.2 photons per millisecond for ranibizumab. There was a statistically significant difference between the 3 medications (P = 0.006). Pairwise analysis of the change in flare showed a statistically significant difference between bevacizumab and ranibizumab (P = 0.002). The change in flare in patients who received aflibercept was not different from that in those who received bevacizumab (P = 0.08) or ranibizumab (P = 0.99).
   Conclusion: There was a statistically significant increase in flare after bevacizumab injection compared with ranibizumab. This difference was small and is not believed to be clinically significant. There was no statistical difference in the change in flare between aflibercept and the other medications, although the number of eyes in the aflibercept group was small.
C1 [Blaha, Gregory R.; Brooks, Nneka O.; Mackel, Charles E.; Pani, Altin; Stewart, Avon P.; Barouch, Fina C.; Chang, Jeffrey; Marx, Jeffrey L.] Lahey Med Ctr, Peabody, MA 01960 USA.
   [Price, Lori L.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
C3 Lahey Hospital & Medical Center; Tufts University
RP Blaha, GR (通讯作者)，Lahey Med Ctr, 1 Essex Ctr Dr, Peabody, MA 01960 USA.
EM gregory.r.blaha@lahey.org
CR [Anonymous], 2006, KOW FM 600 LAS FLAR
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NR 9
TC 9
Z9 9
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 MAR
PY 2015
VL 35
IS 3
BP 577
EP 581
DI 10.1097/IAE.0000000000000334
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CC4AO
UT WOS:000350293100040
PM 25158942
DA 2022-11-30
ER

PT J
AU Ricketti, PA
   Unkle, DW
   Cleri, DJ
   Prenner, JL
   Coluccielo, M
   Ricketti, AJ
AF Ricketti, Peter A.
   Unkle, David W.
   Cleri, Dennis J.
   Prenner, Jonathan L.
   Coluccielo, Michael
   Ricketti, Anthony J.
TI Central serous chorioretinopathy secondary to corticosteroids in
   patients with atopic disease
SO ALLERGY AND ASTHMA PROCEEDINGS
LA English
DT Article
ID A-BEHAVIOR; CHOROIDOPATHY; RETINOPATHY; DETACHMENT; PATHOGENESIS;
   SAFETY; RISK
AB Central serous chorioretinopathy (CSCR) is of unknown etiology and is the most common cause of retinopathy after age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion. Vision loss results from fluid leakage and serail detachment in the macula. Five percent of patients develop chronic CSCR. It is predominantly found in middle-aged men (age-adjusted rates per 100,000: 9.9 for men and 1.7 for women) and is usually unilateral and reversible. Three-quarters of CSCR patients resolve within 3 months but 45% have recurrences, usually with only minor visual acuity changes. Risk factors include type A personality, emotional stress, elevated catecholamines, hypertension, pregnancy, organ transplantation, increased levels of endogenous cortisol, psychopharmacologic medication, use of phosphodiesterase 5 inhibitors, obstructive sleep apnea, Helicobacter pylori infection, or treatment with corticosteroids. Five percent of patients develop chronic disease as a result of subretinal fibrin formation within the blister. CSCR is often bilateral, multifocal, and recurrent, and may be associated with subretinal fibrin formation within the blister. Permanent loss of vision may result from subretinal fibrin-fibrosis with scarring of the macula. Corticosteroid-associated CSCR occurs bilaterally in 20% of patients. Steroid-associated therapy may begin days to years after therapy with any form of drug delivery. We present three atopic patients who presented at various times after oral, inhaled, intranasal, and topical corticosteroid therapy. One patient developed CSCR after three separate types of administration of corticosteroids, which, to our knowledge, has not been observed in the literature.
C1 [Ricketti, Peter A.] Rutgers State Univ, New Jersey Med Sch, Dept Internal Med, Newark, NJ 07102 USA.
   [Unkle, David W.] Catholic Univ Amer, Washington, DC 20064 USA.
   [Cleri, Dennis J.] Seton Hall Univ, Sch Grad Med Educ, S Orange, NJ 07079 USA.
   [Prenner, Jonathan L.] Rutgers State Univ, Robert Wood Johnson Sch Med, Dept Ophthalmol, New Brunswick, NJ 08903 USA.
   [Coluccielo, Michael] South Jersey Eye Phys, Moorestown, NJ USA.
   [Ricketti, Anthony J.] Mercer Allergy & Pulm Associates, Trenton, NJ 08619 USA.
C3 Rutgers State University Newark; Rutgers State University New Brunswick;
   Rutgers State University Medical Center; Catholic University of America;
   Seton Hall University; Rutgers State University New Brunswick; Rutgers
   State University Medical Center
RP Ricketti, AJ (通讯作者)，Mercer Allergy & Pulm Associates, 1544 Kuser Rd,Suite C-6, Trenton, NJ 08619 USA.
EM aricketti@mercerapa.com
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NR 66
TC 9
Z9 9
U1 0
U2 10
PU OCEAN SIDE PUBLICATIONS INC
PI PROVIDENCE
PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA
SN 1088-5412
EI 1539-6304
J9 ALLERGY ASTHMA PROC
JI Allergy Asthma Proc.
PD MAR-APR
PY 2015
VL 36
IS 2
BP 123
EP 129
DI 10.2500/aap.2015.36.3827
PG 7
WC Allergy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Allergy
GA CE5RM
UT WOS:000351893400009
PM 25715240
DA 2022-11-30
ER

PT J
AU Hansson, ML
   Albert, S
   Somermeyer, LG
   Peco, R
   Mejia-Ramirez, E
   Montserrat, N
   Belmonte, JCI
AF Hansson, Magnus L.
   Albert, Silvia
   Gonzalez Somermeyer, Louisa
   Peco, Ruben
   Mejia-Ramirez, Eva
   Montserrat, Nuria
   Izpisua Belmonte, Juan Carlos
TI Efficient Delivery and Functional Expression of Transfected Modified
   mRNA in Human Embryonic Stem Cell-derived Retinal Pigmented Epithelial
   Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DIRECTED DIFFERENTIATION; INNATE IMMUNITY; MITF; ACTIVATION; RPE;
   TRANSPLANTATION; RECOGNITION; TFE3; FATE
AB Gene- and cell-based therapies are promising strategies for the treatment of degenerative retinal diseases such as age-related macular degeneration, Stargardt disease, and retinitis pigmentosa. Cellular engineering before transplantation may allow the delivery of cellular factors that can promote functional improvements, such as increased engraftment or survival of transplanted cells. A current challenge in traditional DNA-based vector transfection is to find a delivery system that is both safe and efficient, but using mRNA as an alternative to DNA can circumvent these major roadblocks. In this study, we show that both unmodified and modified mRNA can be delivered to retinal pigmented epithelial (RPE) cells with a high efficiency compared with conventional plasmid delivery systems. On the other hand, administration of unmodified mRNA induced a strong innate immune response that was almost absent when using modified mRNA. Importantly, transfection of mRNA encoding a key regulator of RPE gene expression, microphthalmia-associated transcription factor (MITE), confirmed the functionality of the delivered mRNA. Immunostaining showed that transfection with either type of mRNA led to the expression of roughly equal levels of MITE, primarily localized in the nucleus. Despite these findings, quantitative RT-PCR analyses showed that the activation of the expression of MITE target genes was higher following toransfection with modified mRNA compared with unmodified mRNA. Our findings, therefore, show that modified mRNA transfection can be applied to human embryonic stem cell-derived RPE cells and that the method is safe, efficient, and functional.
C1 [Hansson, Magnus L.; Albert, Silvia; Gonzalez Somermeyer, Louisa; Peco, Ruben; Mejia-Ramirez, Eva; Montserrat, Nuria] Ctr Regenerat Med Barcelona, Barcelona 08003, Spain.
   [Gonzalez Somermeyer, Louisa] Univ Barcelona, E-08007 Barcelona, Spain.
   [Izpisua Belmonte, Juan Carlos] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.
C3 Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Centro de
   Medicina Regenerativa de Barcelona; University of Barcelona; University
   of Barcelona; Salk Institute
RP Hansson, ML (通讯作者)，Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
EM magnus.l.hansson@ki.se; belmonte@salk.edu
RI Albert, Silvia/P-8231-2015; Montserrat, Nuria/F-3136-2016
OI Albert, Silvia/0000-0002-6921-0351; Montserrat,
   Nuria/0000-0002-1603-1755; Mejia-Ramirez, EVA/0000-0003-1251-5223;
   Gonzalez Somermeyer, Louisa/0000-0001-9139-5383
FU PLE-MINECO [PLE2009-0164]; Moxie Foundation; Leona M. and Harry B.
   Helmsley Charitable Trust [2012-PG-MED002]; G. Harold and Leila Y.
   Mathers Charitable Foundation; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
   [U01HL107442] Funding Source: NIH RePORTER
FX Supported by PLE-MINECO Grant PLE2009-0164, by the Moxie Foundation, by
   Leona M. and Harry B. Helmsley Charitable Trust Grant 2012-PG-MED002,
   and by the G. Harold and Leila Y. Mathers Charitable Foundation. To whom
   correspondence may be addressed: 10010 N. Torrey Pines Rd., La Jolla, CA
   92037. Tel.: 858-453-4100; E-mail: belmonte@salk.edu.
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NR 48
TC 18
Z9 20
U1 1
U2 16
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 27
PY 2015
VL 290
IS 9
BP 5661
EP 5672
DI 10.1074/jbc.M114.618835
PG 12
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA CC0RS
UT WOS:000350044200035
PM 25555917
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Aimjongjun, S
   Sutheerawattananonda, M
   Limpeanchob, N
AF Aimjongjun, Sathid
   Sutheerawattananonda, Manote
   Limpeanchob, Nanteetip
TI Silk lutein extract and its combination with vitamin E reduce
   UVB-mediated oxidative damage to retinal pigment epithelial cells
SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
LA English
DT Article
DE Lutein; Aged related macular degeneration; Retinal pigment epithelial;
   UVB; Oxidative stress; Antioxidant
ID B-INDUCED DAMAGE; MACULAR DEGENERATION; INDUCED APOPTOSIS; DNA-DAMAGE;
   BLUE-LIGHT; IN-VITRO; STRESS; ZEAXANTHIN; XANTHOPHYLLS; RADIATION
AB Increased exposure to solar ultraviolet B (UVB) radiation may promote age related macular degeneration (AMD). Lutein can protect retinal pigment epithelial (RPE) cells from various oxidative insults but its direct protection against UVB has not been reported. This study aimed to demonstrate protective effects of silk lutein extract against UVB-induced oxidative damage to RPE cells and compared with standard lutein and Trolox, a vitamin E analog. ARPE-19 cells were treated with luteins with and without Trolox prior to UVB exposure. Cell viability and apoptosis were determined by trypan blue staining and caspase-3 activity, respectively. Oxidative damage was evaluated by measuring intracellular reactive oxygen species (ROS), lipid peroxidation, and activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase). Levels of lutein remained in culture medium was determined by HPLC. Both luteins reduced cellular ROS levels and lipid peroxidation mediated by UVB, and subsequently increased cell viability and reduced apoptosis. They also restored activities of most tested antioxidant enzymes. Enhancement of lutein antioxidant efficacy was observed in the presence of Trolox. In all these effects, the two lutein preparations had similar effectivenesses. In cell free media, Trolox enhanced the protective effect of lutein probably by reducing its degradation and repairing the oxidized derivatives. Yellow silk cocoon is a potential candidate of lutein for further development as dietary supplement for the prevention of AMD. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Aimjongjun, Sathid; Limpeanchob, Nanteetip] Naresuan Univ, Dept Pharm Practice, Phitsanulok 65000, Thailand.
   [Aimjongjun, Sathid; Limpeanchob, Nanteetip] Naresuan Univ, Pharmacol Res Unit, Ctr Excellence Innovat Chem, Phitsanulok 65000, Thailand.
   [Sutheerawattananonda, Manote] Suranaree Univ Technol, Inst Agr Technol, Sch Food Technol, Nakhon Ratchasima 30000, Thailand.
C3 Naresuan University; Naresuan University; Suranaree University of
   Technology
RP Limpeanchob, N (通讯作者)，Naresuan Univ, Fac Pharmaceut Sci, Phitsanulok 65000, Thailand.
EM nanteetipl@nu.ac.th
FU Agricultural Research Development Agency; Center of Excellence for
   Innovation in Chemistry (PERCH-CIC)
FX The authors thank Dr. Norman Scholfield for manuscript preparation. This
   work was supported by Agricultural Research Development Agency and the
   Center of Excellence for Innovation in Chemistry (PERCH-CIC).
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NR 33
TC 17
Z9 20
U1 1
U2 43
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 1011-1344
J9 J PHOTOCH PHOTOBIO B
JI J. Photochem. Photobiol. B-Biol.
PD JUL 5
PY 2013
VL 124
BP 34
EP 41
DI 10.1016/j.jphotobiol.2013.04.003
PG 8
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 165JA
UT WOS:000320478600004
PM 23651647
DA 2022-11-30
ER

PT J
AU Oldmeadow, C
   Riveros, C
   Holliday, EG
   Scott, R
   Moscato, P
   Wang, JJ
   Mitchell, P
   Buitendijk, GHS
   Vingerling, JR
   Klaver, CCW
   Klein, R
   Attia, J
AF Oldmeadow, Christopher
   Riveros, Carlos
   Holliday, Elizabeth G.
   Scott, Rodney
   Moscato, Pablo
   Wang, Jie Jin
   Mitchell, Paul
   Buitendijk, Gabrielle H. S.
   Vingerling, Johannes R.
   Klaver, Caroline C. W.
   Klein, Ronald
   Attia, John
TI Sifting the wheat from the chaff: prioritizing GWAS results by
   identifying consistency across analytical methods
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE genome-wide association study; age-related macular degeneration
ID AGE-RELATED MACULOPATHY; GENOME-WIDE ASSOCIATION; COMPLEMENT FACTOR-H;
   MACULAR DEGENERATION; FAMILIAL AGGREGATION; SUSCEPTIBILITY LOCI;
   EXTENDED FAMILIES; SCAN; GENE; RISK
AB The curse of multiple testing has led to the adoption of a stringent Bonferroni threshold for declaring genome-wide statistical significance for any one SNP as standard practice. Although justified in avoiding false positives, this conservative approach has the potential to miss true associations as most studies are drastically underpowered. As an alternative to increasing sample size, we compare results from a typical SNP-by-SNP analysis with three other methods that incorporate regional information in order to boost or dampen an otherwise noisy signal: the haplotype method (Schaid et al. [2002] Am J Hum Genet 70:425434), the gene-based method (Liu et al. [2010] Am J Hum Genet 87:139145), and a new method (interaction count) that uses genome-wide screening of pairwise SNP interactions. Using a modestly sized case-control study, we conduct a genome-wide association studies (GWAS) of age-related macular degeneration, and find striking agreement across all methods in regions of known associated variants. We also find strong evidence of novel associated variants in two regions (Chromosome 2p25 and Chromosome 10p15) in which the individual SNP P-values are only suggestive, but where there are very high levels of agreement between all methods. We propose that consistency between different analysis methods may be an alternative to increasingly larger sample sizes in sifting true signals from noise in GWAS. Genet. Epidemiol. 2011. (C) 2011 Wiley Periodicals, Inc. 35:745-754, 2011
C1 [Oldmeadow, Christopher; Holliday, Elizabeth G.; Attia, John] Newcastle Univ, Sch Med & Publ Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Oldmeadow, Christopher; Riveros, Carlos; Holliday, Elizabeth G.; Scott, Rodney; Moscato, Pablo; Attia, John] John Hunter Hosp, Hunter Med Res Inst, New Lambton Hts, NSW, Australia.
   [Riveros, Carlos; Moscato, Pablo] Newcastle Univ, Ctr Bioinformat Biomarker Discovery & Informat Ba, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Moscato, Pablo] Australian Res Council, Ctr Excellence Bioinformat, Canberra, ACT, Australia.
   [Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Westmead Millennium Inst, Ctr Vision Res, Dept Ophthalmol, Sydney, NSW 2006, Australia.
   [Wang, Jie Jin] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Wang, Jie Jin] Univ Melbourne, Dept Ophthalmol, Melbourne, Vic, Australia.
   [Buitendijk, Gabrielle H. S.; Vingerling, Johannes R.; Klaver, Caroline C. W.] Erasmus MC, Dept Epidemiol, Dept Ophthalmol, Rotterdam, Netherlands.
   [Klein, Ronald] Univ Wisconsin, Dept Ophthalmol, Madison, WI USA.
C3 Newcastle University - UK; Hunter Medical Research Institute; John
   Hunter Hospital; University of Newcastle; Newcastle University - UK;
   University of Sydney; Westmead Institute for Medical Research; Centre
   for Eye Research Australia; University of Melbourne; University of
   Melbourne; Erasmus University Rotterdam; Erasmus MC; University of
   Wisconsin System; University of Wisconsin Madison
RP Oldmeadow, C (通讯作者)，Newcastle Univ, Sch Med & Publ Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
EM christoper.oldmeadow@newcastle.edu.au
RI Wang, Jie Jin/P-1499-2014; Attia, John R/F-5376-2013; Riveros,
   Carlos/F-3373-2012; Riveros, Carlos/A-6880-2013; Mitchell,
   Paul/P-1498-2014; wang, jie/GRS-0942-2022; Klaver, Caroline
   C.W./A-2013-2016; MOSCATO, PABLO ALBERTO/G-7668-2013; Scott,
   Rodney/B-2827-2013
OI Wang, Jie Jin/0000-0001-9491-4898; Attia, John R/0000-0001-9800-1308;
   Riveros, Carlos/0000-0002-2551-7618; Oldmeadow,
   Christopher/0000-0001-6104-1322; Scott, Rodney/0000-0001-7724-3404;
   Moscato, Pablo/0000-0003-2570-5966; Klaver,
   Caroline/0000-0002-2355-5258; Klein, Ronald/0000-0002-4428-6237
FU National Health and Medical Research Council [512423]
FX Contract grant sponsor: National Health and Medical Research Council;
   Contract grant number: 512423.
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NR 34
TC 8
Z9 8
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2011
VL 35
IS 8
BP 745
EP 754
DI 10.1002/gepi.20622
PG 10
WC Genetics & Heredity; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Mathematical & Computational Biology
GA 854BD
UT WOS:000297468600001
PM 22125219
DA 2022-11-30
ER

PT J
AU Muscio, A
   Ciriaci, D
   Cruciani, F
AF Muscio, A.
   Ciriaci, D.
   Cruciani, F.
TI A simulation of cost-benefit analysis of blindness prevention in Italy
SO CLINICA TERAPEUTICA
LA English
DT Article
DE age-related macular degeneration; cataract; diabetic retinopathy;
   glaucoma; net present value (NPV); government spending; prevention
AB Purpose. The most important purpose is to assess by a trial and error method the financial effects of efficient prevention programmes in our country. The study provides an empiric evidence that Government could reduce public spending thorough investments in projects of prevention about visual care.
   Materials and methods. Authors focus on the economic impact of four eye diseases that are the major cause of blindness (90%) and for this reason they were classificated as 'diseases of social importance' (DSI from herefonh) according to the WHO: Age related Macular Degeneration (AMD), Glaucoma, Diabetic Retinopathy (DR), Cataract. Authors use a three-stage approach in order to estimate the impact of blindness prevention on public accounts:
   1. Calculation of aggregate costs of the DSI in Italy;
   2. Use of the estimated figures in the first stage of the alanysis to estimate the individual average costs;
   3. Use of the estimated figures in the second stage of the analysis to run a simulation in capital budgeting comparing the costs associated with taking one of two possible choices: investing or not in a blindness prevention programme.
   Discussion: Authors simulate the economic effects of the adoption of a blindness prevention campaign and compare them to the calculated costs of blindness. This comparison was based on the creation of decision trees, which are typically used for the optimisation of investment portfolios, combined with another decision technique: the Net Present Value (NPV). Clin Ter 2011; 162(6):e187-194
C1 [Cruciani, F.] Univ Roma La Sapienza, IAPB, Italian Branch, Head Neck Dept, Rome, Italy.
   [Muscio, A.] Univ Foggia, Dept Econ Math & Stat Sci DSEMS, Foggia, Italy.
   [Ciriaci, D.] Commiss European Communities, Directorate Gen JRC, IPTS, Seville, Spain.
C3 Sapienza University Rome; University of Foggia; European Commission
   Joint Research Centre; EC JRC Institute for Prospective Technological
   Studies (IPTS)
RP Cruciani, F (通讯作者)，Univ Roma La Sapienza, Clin Oculist, Dipartimento Organi Senso, Rome, Italy.
EM filippo.cruciani@uniroma1.it
RI Muscio, Alessandro/A-6720-2015; Muscio, Alessandro/P-5463-2019
OI Muscio, Alessandro/0000-0001-5186-2522; Muscio,
   Alessandro/0000-0001-5186-2522
CR Frick KD, 2003, AM J OPHTHALMOL, V135, P471, DOI 10.1016/S0002-9394(02)02110-4
   Frick KD, 2005, ARCH OPHTHALMOL-CHIC, V123, P239, DOI 10.1001/archopht.123.2.239
   Frick KD, 2007, ARCH OPHTHALMOL, V125
   Grainger J., 2003, COSTS BLINDNESS ANAL
   Gravitas Research and Strategy Ltd e Market Economics Ltd, 2006, COST BLINDN NZ
   ISTAT, 2007, STAT TRASP FERR 2004
   ISTAT, 2007, IND AMB URB 2007 200
   Istituto Nazionale di Statistica (ISTAT), 2007, IND MULT FAM COND SA
   Meads C, 2003, BRIT J OPHTHALMOL, V87, P1201, DOI 10.1136/bjo.87.10.1201
   WHO, 2006, WORLD HLTH REP
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NR 11
TC 2
Z9 2
U1 0
U2 4
PU SOC EDITRICE UNIV
PI ROME
PA VIA G B MORGAGNI 1, ROME, 10061, ITALY
SN 0009-9074
J9 CLIN TER
JI Clin. Ter.
PD NOV-DEC
PY 2011
VL 162
IS 6
BP E187
EP E194
PG 8
WC Medicine, General & Internal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Pharmacology & Pharmacy
GA 882TU
UT WOS:000299587600020
PM 22262339
DA 2022-11-30
ER

PT J
AU Sasamoto, Y
   Gomi, F
   Sawa, M
   Sakaguchi, H
   Tsujikawa, M
   Nishida, K
AF Sasamoto, Yuzuru
   Gomi, Fumi
   Sawa, Miki
   Sakaguchi, Hirokazu
   Tsujikawa, Motokazu
   Nishida, Kohji
TI Effect of Cataract in Evaluation of Macular Pigment Optical Density by
   Autofluorescence Spectrometry
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; JAPANESE POPULATION; HEALTHY-SUBJECTS; PRIMATE
   RETINAS; OCULAR MEDIA; RISK-FACTORS; DEGENERATION; ZEAXANTHIN; LUTEIN;
   LIGHT
AB PURPOSE. To assess the effect of cataract on the evaluation of macular pigment optical density (MPOD) in aged patients.
   METHODS. MPOD was prospectively measured using autofluorescence spectrometry before and after cataract surgery. The Lens Opacities Classification System III was used to grade the cataracts at baseline.
   RESULTS. Forty-five eyes of 41 subjects, who had no ocular disorders or fundus autofluorescence abnormalities except for age-related nuclear cataract, were included. Preoperative MPOD was 0.350 +/- 0.117 density unit (DU). Regression analysis showed that a higher nuclear color score correlated with lower MPOD (t = -2.90, P = 0.0063). The preoperative MPOD prediction formula was MPOD = 0.545 - 0.069 X nuclear color score. A higher nuclear color score correlated significantly with failure to measure the MPOD (chi(2) = 5.08, P = 0.0242). The mean postoperative MPOD was 0.600 DU (95% confidence interval [CI], 0.562-0.637), which was significantly (P < 0.0001) higher than the preoperative level of 0.350 DU (95% CI, 0.313-0.388). Regression analysis showed that higher preoperative MPOD correlated with higher postoperative MPOD (t = 2.91, P = 0.0061).
   CONCLUSIONS. Cataract, especially its nuclear component, affects MPOD measured by autofluorescence spectrometry. Care should be taken when using this method in eyes with age-related macular maculopathy and age-related macular degeneration and in older patients who may develop these diseases. (Invest Ophthalmol Vis Sci. 2011;52:927-932) DOI:10.1167/iovs.10-5664
C1 [Sasamoto, Yuzuru; Gomi, Fumi; Sawa, Miki; Sakaguchi, Hirokazu; Tsujikawa, Motokazu; Nishida, Kohji] Osaka Univ, Grad Sch Med, Dept Ophthalmol, Suita, Osaka 5650871, Japan.
C3 Osaka University
RP Gomi, F (通讯作者)，Osaka Univ, Grad Sch Med, Dept Ophthalmol, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM fgomi@ophthal.med.osaka-u.ac.jp
OI Nishida, Kohji/0000-0001-9069-3610; Gomi, Fumi/0000-0003-0807-8817
FU Bausch & Lomb Japan, Ltd., Tokyo, Japan
FX Supported in part by Bausch & Lomb Japan, Ltd., Tokyo, Japan.
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NR 42
TC 27
Z9 28
U1 1
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 FEB
PY 2011
VL 52
IS 2
BP 927
EP 932
DI 10.1167/iovs.10-5664
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 728AQ
UT WOS:000287846300040
PM 21071730
DA 2022-11-30
ER

PT J
AU Polito, A
   Cereda, M
   Romanelli, F
   Pertile, G
AF Polito, A.
   Cereda, M.
   Romanelli, F.
   Pertile, G.
TI Macular translocation with 360 degrees retinotomy for management of
   retinal pigment epithelial tear: long-term results
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID INTRAVITREAL BEVACIZUMAB; CHOROIDAL NEOVASCULARIZATION; DEGENERATION;
   INJECTION; RANIBIZUMAB; THERAPY; AVASTIN
AB Background To determine long-term functional and morphological changes after full macular translocation (FMT) with 360 degrees retinotomy in patients with retinal pigment epithelium (RPE) tears, in light of the increasing number of reports of this complication following vascular endothelial growth factor (VEGF)-modulating therapy.
   Methods We retrospectively reviewed a consecutive series of six patients with RPE tears secondary to neovascular age-related macular degeneration who underwent FMT with 360 degrees retinotomy between March 2005 and June 2006. Preoperative and postoperative visual acuity, fundus fluorescein angiography (FA) and optical coherence tomography (OCT) were reviewed. RPE tears occurred spontaneously in three cases and after intravitreal triamcinolone in three cases. Preoperative and postoperative best-corrected visual acuity was converted to logarithm of the minimal angle of resolution visual acuity for analysis.
   Results Mean postoperative follow-up was 39 months (range 36-50 months). At 12, 24 and 36 months mean visual acuity increased by 6.00 (5.3), 5.57 (5.54) and 6.67 (4.76) lines, respectively. This improvement was maintained at final examination. FA and OCT revealed pigment epithelium atrophy extending to the new fovea in one case only, which also had longer symptom duration.
   Conclusions Long-term follow-up of FMT showed significant improvement in the majority of patients. FMT may be an option for cases of RPE tears of recent onset. Further investigations are necessary to determine FMT's role in tears developing during the course of anti-VEGF therapy.
C1 [Polito, A.; Cereda, M.; Romanelli, F.; Pertile, G.] Osped S Cuore Don Calabria, Dept Ophthalmol, Verona, Italy.
C3 IRCCS Sacro Cuore Don Calabria
RP Polito, A (通讯作者)，Osped S Cuore Don Calabria, Dept Ophthalmol, Via Don Sempreboni 5, I-37024 Negrar, Italy.
EM apolito23@yahoo.it
RI Pertile, Grazia/AAC-4956-2022
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NR 25
TC 15
Z9 16
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 JAN
PY 2011
VL 95
IS 1
BP 74
EP 78
DI 10.1136/bjo.2009.170381
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 695OB
UT WOS:000285380300015
PM 20576765
DA 2022-11-30
ER

PT J
AU Lyzogubov, VV
   Tytarenko, RG
   Jha, P
   Liu, JA
   Bora, NS
   Bora, PS
AF Lyzogubov, Valeriy V.
   Tytarenko, Ruslana G.
   Jha, Purushottam
   Liu, Juan
   Bora, Nalini S.
   Bora, Puran S.
TI Role of Ocular Complement Factor H in a Murine Model of Choroidal
   Neovascularization
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; MOUSE MODEL; ALTERNATIVE PATHWAY; TARGETED
   INHIBITOR; ACTIVATION; POLYMORPHISM; EXPRESSION; Y402H;
   IMMUNOFLUORESCENCE; ANGIOGENESIS
AB The objective of this study was to explore the relationship between local (ie, ocular) complement factor H (CFH) and choroidal neovascularization (CNV) associated with wet age-related macular degeneration (AMD), a leading cause of irreversible blindness, in laser-treated C57BL/6 mice. Immunohistochemical and RT-PCR analysis of retinal pigmented epithelium (RPE)-choroid sclera revealed that the expression of CFH was down-regulated on day 1 with a dramatic increase on days 5 and 7 postlaser injury. Flat mount and Western blot analysis further revealed that membrane attack complex (MAC) expression was up-regulated on days 1 and 3 postlaser injury; however, MAC was down-regulated on days 5 and 7 postinjury but was still higher than in non-injured mice Similar patterns for CFH and MAC were observed for RPE cells when serial paraffin sections of the laser spots were analyzed. Subretinal injection of siRNA directed against CFH resulted in a threefold suppression of CFH in the RPE and choroid without affecting either CFH levels in the liver or the functional activity of the alternative pathway in the peripheral blood. Ocular knock-down of CFH resulted in increased MAC deposition, which leads to the early onset as well as exacerbation of laser-induced CNV. In conclusion, our findings provide evidence that CFH present on RPE and choroid regulates local MAC formation that is critical for the development of laser-induced CNV. (Am J Pathol 2010, 177:1870-1880 DOI: 10.2353/ajpath.2010.091168)
C1 [Lyzogubov, Valeriy V.; Tytarenko, Ruslana G.; Jha, Purushottam; Liu, Juan; Bora, Nalini S.; Bora, Puran S.] Univ Arkansas Med Sci, Dept Ophthalmol, Jones Eye Inst, Pat & Willard Walker Eye Res Ctr, Little Rock, AR 72205 USA.
C3 University of Arkansas System; University of Arkansas Medical Sciences
RP Bora, NS (通讯作者)，Univ Arkansas Med Sci, Dept Ophthalmol, Jones Eye Inst, Pat & Willard Walker Eye Res Ctr, 4301 W Markham,Mail Slot 523, Little Rock, AR 72205 USA.
EM nbora@uams.edu; pbora@uams.edu
RI Mohammed, Imran/J-8271-2012
OI Mohammed, Imran/0000-0002-8412-0768; Bora, Puran/0000-0003-4781-1217
FU National Institutes of Health (NIH) [EY014623, EY016205, 2P20 RR16460];
   University of Arkansas for Medical Sciences; NIH/National Center for
   Research Resources [1 S10 RR 19395]; NATIONAL CENTER FOR RESEARCH
   RESOURCES [P20RR016460, S10RR019395] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R01EY016205, R01EY014623] Funding Source: NIH
   RePORTER
FX Supported by National Institutes of Health (NIH) grants EY014623 and
   EY016205, and grants from University of Arkansas for Medical Sciences,
   Little Rock, AR. The use of the facilities in the University of Arkansas
   for Medical Sciences Digital and Confocal Microscopy Laboratory was
   supported by NIH grant 2P20 RR16460 and NIH/National Center for Research
   Resources grant 1 S10 RR 19395.
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NR 44
TC 37
Z9 38
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD OCT
PY 2010
VL 177
IS 4
BP 1870
EP 1880
DI 10.2353/ajpath.2010.091168
PG 11
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 658NG
UT WOS:000282496100030
PM 20813971
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Rabenlehner, D
   Stanzel, BV
   Krebs, I
   Binder, S
   Goll, A
AF Rabenlehner, Doris
   Stanzel, Boris V.
   Krebs, Ilse
   Binder, Susanne
   Goll, Alexandra
TI Reduction of iatrogenic RPE lesions in AMD patients: evidence for wound
   healing?
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE retinal pigment epithelium; wound healing; age-related macular
   degeneration; fundus autofluorescence
ID RETINAL-PIGMENT EPITHELIUM; HUMAN BRUCHS MEMBRANE; MACULAR DEGENERATION;
   FUNDUS AUTOFLUORESCENCE; IN-VIVO; CLINICOPATHOLOGICAL CORRELATION;
   NEOVASCULAR MEMBRANES; OCULAR FUNDUS; TRANSPLANTATION; DEBRIDEMENT
AB Purpose Our purpose was to study retinal pigment epithelium (RPE) wound healing in patients with age-related macular degeneration (AMD).
   Patients and methods Abrasive debridement of nasal RPE was performed with a metal cannula during pars plana vitrectomy for foveal choroidal neovascularization (CNV) membrane excision combined with simultaneous autologous RPE transplantation. Fundus autofluorescence, fluorescein angiography images, and red-free pictures were taken initially within 1-2 weeks postoperatively, subsequently in 2-week intervals until 3 months, monthly until 6 months, and every 3 months thereafter. The borders of these lesions were measured; areas were calculated and compared using ArchiCad Software. Fourteen eyes of 14 patients suffering from AMD were included (nine women and four men, mean age 75.6 years +/- 6.6 years).
   Results Six of 14 (42.9 %) patients showed a reduction of the RPE debrided area. The size of these lesions reduced 5.6-20% within 2 postoperative months compared with their size at first examination (from a mean of 13.7 mm2 +/- 7.2 at baseline to a mean of 12.8 mm2 +/- 6.7 at 2 months postoperatively). No further reduction of the lesions was seen after the 2 months. In eight cases, borders of the RPE debrided areas stayed stable during observation time.
   Conclusions Wound healing of abrasively debrided RPE monolayer defects in patients with AMD occurs to a certain extent in nearly half of the cases. This process seems to stop after 2 months.
C1 [Rabenlehner, Doris] Bolton Inst Retinol & Biomicroscop Laser Surg, A-1030 Vienna, Austria.
   [Rabenlehner, Doris; Stanzel, Boris V.; Krebs, Ilse; Binder, Susanne] Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, Vienna, Austria.
   [Rabenlehner, Doris; Krebs, Ilse; Binder, Susanne] Rudolph Fdn Clin, Dept Ophthalmol, Vienna, Austria.
   [Stanzel, Boris V.] Stanford Univ, Sch Med, Dept Ophthalmol, Stanford, CA 94305 USA.
   [Goll, Alexandra] Med Univ Vienna, Med Stat Inst, Vienna, Austria.
C3 Ludwig Boltzmann Institute; Stanford University; Medical University of
   Vienna
RP Rabenlehner, D (通讯作者)，Bolton Inst Retinol & Biomicroscop Laser Surg, Juchgasse 25, A-1030 Vienna, Austria.
EM doris.rabenlehner@mediatrain.at
RI Stanzel, Boris/ADP-9221-2022; Stanzel, Boris/AAG-7010-2022
OI Stanzel, Boris/0000-0002-4316-1539; Stanzel, Boris/0000-0002-4316-1539;
   Graf, Alexandra/0000-0003-0035-2658
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NR 48
TC 9
Z9 9
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 MAR
PY 2008
VL 246
IS 3
BP 345
EP 352
DI 10.1007/s00417-007-0658-6
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 260DW
UT WOS:000252992000004
PM 17704936
DA 2022-11-30
ER

PT J
AU Chang, Y
   Lee, FL
   Chen, SJ
   Chen, SF
AF Chang, Y
   Lee, FL
   Chen, SJ
   Chen, SF
TI Optical measurement of human retinal macular pigment and its spatial
   distribution with age
SO MEDICAL PHYSICS
LA English
DT Article
DE age; macular pigment; spatial distribution; imaging fundus reflectometry
ID NERVE-FIBER LAYER; HUMAN OCULAR FUNDUS; SPECTRAL REFLECTANCE;
   DIRECTIONAL REFLECTANCE; FLICKER PHOTOMETRY; PRIMATE RETINAS; HUMAN-EYE;
   DENSITY; REFLECTOMETRY; IDENTIFICATION
AB The existence of macular pigment (MP) in human eyes has been found to be of importance in the prevention of age-related macular degeneration (ARMD). A noninvasive technique of two-wavelength imaging fundus reflectometry was developed to measure the density distribution of this yellow pigment in retina in vivo. A total of 55 healthy human subjects were recruited and divided into three groups with average ages and sample sizes of 25.2 +/- 2.1 (N = 25), 40.2 +/- 8.3 (N = 13), and 67.5 +/- 7.1 years (N = 17), respectively. Only the MP distributions in the horizontal meridian of retinas are presented in this report. The results show that the average peak optical density of MP are 0.23 +/- 0.07, 0.21 +/- 0.05, and 0.25 +/- 0.06 from young to old groups, respectively. No significant difference is shown in the statistical t-test between the groups of the peak MP density. The half width of MP spatial distribution (HWMPD) are 4.8degrees +/- 1.5degrees, 5.1degrees +/- 2.1degrees and 7.7degrees +/- 2.0degrees (1degrees approximate to 0.3 mm) from young to old groups, respectively. Mean HWMPD approximate to 5.6degrees +/- 2.1degrees. It shows that the area of MP is increased approximately by a rate of 0.06degrees/yr according to the application of linear regression. However, the cause of the MP extension in the retina with age is unknown. (C) 2002 American Association of Physicists in Medicine.
C1 Natl Yang Ming Univ, Inst Biomed Engn, Taipei 11221, Taiwan.
   Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei 11211, Taiwan.
C3 National Yang Ming Chiao Tung University; Taipei Veterans General
   Hospital
RP Chang, Y (通讯作者)，Natl Yang Ming Univ, Inst Biomed Engn, Taipei 11221, Taiwan.
EM ychang@bme.ym.edu.tw
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NR 52
TC 17
Z9 17
U1 0
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0094-2405
EI 2473-4209
J9 MED PHYS
JI Med. Phys.
PD NOV
PY 2002
VL 29
IS 11
BP 2621
EP 2628
DI 10.1118/1.1515761
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Radiology, Nuclear Medicine & Medical Imaging
GA 617CG
UT WOS:000179342200020
PM 12462729
DA 2022-11-30
ER

PT J
AU Margalit, E
   Maia, M
   Weiland, JD
   Greenberg, RJ
   Fujii, GY
   Torres, G
   Piyathaisere, DV
   O'Hearn, TM
   Liu, WT
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   Dagnelie, G
   Scribner, DA
   de Juan, E
   Humayun, MS
AF Margalit, E
   Maia, M
   Weiland, JD
   Greenberg, RJ
   Fujii, GY
   Torres, G
   Piyathaisere, DV
   O'Hearn, TM
   Liu, WT
   Lazzi, G
   Dagnelie, G
   Scribner, DA
   de Juan, E
   Humayun, MS
TI Retinal prosthesis for the blind
SO SURVEY OF OPHTHALMOLOGY
LA English
DT Review
DE artificial vision; blindness; cortical prosthesis; electrical
   stimulation; electronic implants; macular degeneration; optic nerve;
   optic nerve prosthesis; retina; retinal prosthesis; retinitis
   pigmentosa; visual cortex; visual prosthesis
ID ELECTRICALLY-EVOKED RESPONSE; CENTRAL-NERVOUS-SYSTEM; VISUAL-SYSTEM;
   STIMULUS PARAMETERS; INTRACORTICAL MICROSTIMULATION; SUBRETINAL
   MICROPHOTODIODES; MORPHOMETRIC-ANALYSIS; RETINITIS-PIGMENTOSA; CHARGE
   INJECTION; ELECTRODE ARRAY
AB Most of current concepts for a visual prosthesis are based on neuronal electrical stimulation at different locations along the visual pathways within the central nervous system. The different designs of Visual prostheses are named according to their locations (i.e., cortical, optic nerve, subretinal, and epiretinal). Visual loss caused by outer retinal degeneration in diseases such as retinitis pigmentosa or age-related macular degeneration can be reversed by electrical Stimulation of the retina or the optic nerve (retinal or optic nerve prostheses, respectively). On the other hand, Visual loss caused by inner or whole thickness retinal diseases, eye loss, optic nerve diseases (tumors, ischemia, inflammatory processes etc.), or diseases of the central nervous system (not including diseases of the primary and secondary visual cortices) can be reversed by a cortical visual prosthesis. The intent of this article is to provide an overview of current and future concepts of retinal and optic nerve prostheses. This article will begin with general considerations that are related to all Or most Of visual prostheses and then concentrate on the retinal and optic nerve designs. The authors believe that the field has grown beyond the scope of a single article so cortical prostheses will be described only because of their direct effect oil the concept and technical development of the other prostheses, and this will be done in a more general and historic perspective.. (C) 2002 by Elsevier Science Inc. All rights reserved.
C1 Wilmer Eye Inst, Intraocular Prosthesis Grp, Baltimore, MD USA.
   Second Sight LLC, Valencia, CA USA.
   N Carolina State Univ, Dept Elect & Comp Engn, Raleigh, NC 27695 USA.
   USN, Res Lab, Washington, DC 20375 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; University of North
   Carolina; North Carolina State University; United States Department of
   Defense; United States Navy; Naval Research Laboratory
RP Humayun, MS (通讯作者)，Wilmer Ophthalmol Inst, Maumenee 738,600 N Wolf St, Baltimore, MD 21287 USA.
RI Maia, Mauricio/I-5892-2015
OI Maia, Mauricio/0000-0002-7034-8091; Weiland, James/0000-0003-3453-9074
FU NEI NIH HHS [R01 EY012843, R24EY12893-01, R209EY11888] Funding Source:
   Medline; NATIONAL EYE INSTITUTE [R01EY012843, R29EY011888, R24EY012893]
   Funding Source: NIH RePORTER
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NR 171
TC 312
Z9 345
U1 4
U2 85
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0039-6257
EI 1879-3304
J9 SURV OPHTHALMOL
JI Surv. Ophthalmol.
PD JUL-AUG
PY 2002
VL 47
IS 4
BP 335
EP 356
AR PII S0039-6257(02)00311-9
DI 10.1016/S0039-6257(02)00311-9
PG 22
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 581MN
UT WOS:000177296300002
PM 12161210
DA 2022-11-30
ER

PT J
AU Ullah, H
   Faran, M
   Batool, Z
   Nazir, A
   Gilanie, G
   Amin, N
AF Ullah, H.
   Faran, M.
   Batool, Z.
   Nazir, A.
   Gilanie, G.
   Amin, N.
TI Diagnosis of Ocular Diseases Using Optical Coherence Tomography (OCT) at
   lambda=840 nm
SO LASERS IN ENGINEERING
LA English
DT Article
DE Superluminescent diode (SLD) laser; optical coherence tomography (OCT);
   retina; optic nerve; eye disease; optical coherence tomography
   segmentation and evaluation (OCTSEG); graphical interface for medical
   image analysis and simulation (GIMIAS)
AB Optical coherence tomography (OCT) is an imaging technique performed without any incision in the body and has a significant importance in biomedical diagnostics. OCT has been extensively used for early diagnose of ocular disease by obtaining two-dimensional (2-D) and three-dimensional (3-D) images. Using OCT with a superluminescent diode (SLD) laser with a wavelength, lambda, of 840 nm we identified problems in the retina and optic nerve. OCT data set images were obtained from Sankara Nethralaya (SN) Eye Hospital, Chennai, India using a high-definition (HD)-OCT machine with a scan length of 2 mm and a raster scan protocol containing 512 x 1024 pixels for the identification of ocular diseases such as macular hole (MH), diabetic retinopathy (DR), age-related macular degeneration (AMD) and central serous retinopathy (CSR) for different patients of different ages. These images were processed using two different software packages: optical coherence tomography segmentation and evaluation (OCTSEG); and graphical interface for medical image analysis and simulation (GIMIAS) for further identification of fluid accumulation, vessel collapse, layer breakage and fluid drainage. OCTSEG was used to identify and separate different five layers. Each layer has been distinguished with colour. GIMIAS was used to colourize OCT images which can help us to observe and diagnose different problems in the layers. Each colourization has different benefit. Using this software, different area of a diseased eye can be easily detected. Finally, the comparison of three types of images made this diagnosis easier and clear.
C1 [Ullah, H.; Faran, M.; Batool, Z.; Nazir, A.] Islamia Univ Bahawalpur, Dept Phys, Biophoton Imaging Tech Lab BITL, Bahawalpur, Pakistan.
   [Gilanie, G.] Islamia Univ Bahawalpur, Dept Comp Sci, Bahawalpur, Pakistan.
   [Amin, N.] COMSATS Univ Islamabad, Dept Phys, Lahore Campus,1-5 KM Def Rd,Off Raiwind Rd, Lahore, Pakistan.
C3 Islamia University of Bahawalpur; Islamia University of Bahawalpur;
   COMSATS University Islamabad (CUI)
RP Ullah, H (通讯作者)，Islamia Univ Bahawalpur, Dept Phys, Biophoton Imaging Tech Lab BITL, Bahawalpur, Pakistan.
EM hafeezullah@iub.edu.pk
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NR 10
TC 0
Z9 0
U1 0
U2 0
PU OLD CITY PUBLISHING INC
PI PHILADELPHIA
PA 628 NORTH 2ND ST, PHILADELPHIA, PA 19123 USA
SN 0898-1507
EI 1029-029X
J9 LASER ENG
JI Laser Eng.
PY 2022
VL 53
IS 1-2
BP 73
EP 85
PG 13
WC Materials Science, Multidisciplinary; Optics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Materials Science; Optics
GA 2D9AK
UT WOS:000811830500005
DA 2022-11-30
ER

PT J
AU Yang, X
   Rai, U
   Chung, JY
   Esumi, N
AF Yang, Xue
   Rai, Usha
   Chung, Jin-Yong
   Esumi, Noriko
TI Fine Tuning of an Oxidative Stress Model with Sodium Iodate Revealed
   Protective Effect of NF-kappa B Inhibition and Sex-Specific Difference
   in Susceptibility of the Retinal Pigment Epithelium
SO ANTIOXIDANTS
LA English
DT Article
DE retinal pigment epithelium; sodium iodate; oxidative stress; IKKbeta;
   NF-kappaB; sex differences; anti-oxidant; catalase
ID IKK-BETA; MESENCHYMAL TRANSITION; MACULAR DEGENERATION; CATALASE;
   KINASE; TRANSCRIPTION; INJURY; INFLAMMATION; ACTIVATION; EXPRESSION
AB Oxidative stress of the retinal pigment epithelium (RPE) is a major risk factor for age-related macular degeneration (AMD). As a dry AMD model via oxidative stress, sodium iodate (NaIO3), which is primarily toxic to the RPE, has often been used at a high dose to cause RPE death for studying photoreceptor degeneration. Thus, characterization of RPE damage by a low dose of NaIO3 is still limited. To quantify RPE damage caused by NaIO3 in mice, we recently developed a morphometric method using RPE flat-mounts. Here, we report that NaIO3 has a narrow range of dose-effect correlation at 11-18 mg/kg body weight in male C57BL/6J mice. We evaluated the usefulness of our quantification method in two experimental settings. First, we tested the effect of NF-kappa B inhibition on NaIO3-induced RPE damage in male C57BL/6J mice. IKK beta inhibitor BAY 651942 suppressed upregulation of NF-kappa B targets and protected the RPE from oxidative stress. Second, we tested sex-specific differences in NaIO3-induced RPE damage in C57BL/6J mice using a low dose near the threshold. NaIO3 caused more severe RPE damage in female mice than in male mice. These results demonstrate the usefulness of the quantification method and the importance of fine-tuning of the NaIO3 dose. The results also show the therapeutic potential of IKK beta inhibition for oxidative stress-related RPE diseases, and reveal previously-unrecognized sex-specific differences in RPE susceptibility to oxidative stress.
C1 [Yang, Xue; Rai, Usha; Chung, Jin-Yong; Esumi, Noriko] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Smith Bldg,Room 3041,400 North Broadway, Baltimore, MD 21231 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Esumi, N (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Smith Bldg,Room 3041,400 North Broadway, Baltimore, MD 21231 USA.
EM xyangcelia@gmail.com; urai2@jhmi.edu; jchung9@jhmi.edu; nesumi1@jhmi.edu
FU BrightFocus Foundation [M2015220]; US National Institutes of Health
   [P30EY001765]; Wilmer Pooled Professor Research Fund; Research to
   Prevent Blindness, Inc; Johns Hopkins University/Wilmer Eye Institute
   [WILM003]
FX This work was supported by research grants from the BrightFocus
   Foundation (M2015220 to N.E.), the US National Institutes of Health
   (P30EY001765 to Wilmer Eye Institute), an award from Wilmer Pooled
   Professor Research Fund (PPF 2016 to N.E.), and the Research to Prevent
   Blindness, Inc. (unrestricted funds to Wilmer Eye Institute). Part of
   this work was also funded through a research grant from Bayer AG to
   Johns Hopkins University/Wilmer Eye Institute (WILM003).
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NR 76
TC 0
Z9 0
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD JAN
PY 2022
VL 11
IS 1
AR 103
DI 10.3390/antiox11010103
PG 20
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 YO8WH
UT WOS:000748213800001
PM 35052607
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Ng, WY
   Zhang, SA
   Wang, ZR
   Ong, CJT
   Gunasekeran, DV
   San Lim, GY
   Zheng, FH
   Tan, SCY
   Tan, GSW
   Rim, TH
   Schmetterer, L
   Ting, DSW
AF Ng, Wei Yan
   Zhang, Shihao
   Wang, Zhaoran
   Ong, Charles Jit Teng
   Gunasekeran, Dinesh, V
   San Lim, Gilbert Yong
   Zheng, Feihui
   Tan, Shaun Chern Yuan
   Tan, Gavin Siew Wei
   Rim, Tyler Hyungtaek
   Schmetterer, Leopold
   Ting, Daniel Shu Wei
TI Updates in deep learning research in ophthalmology
SO CLINICAL SCIENCE
LA English
DT Review
ID MAJOR RISK-FACTORS; ARTIFICIAL-INTELLIGENCE; DIABETIC-RETINOPATHY;
   GLOBAL PREVALENCE; MACULAR DEGENERATION; COST-EFFECTIVENESS; AUTOMATED
   DETECTION; PREDICTION; HEALTH; MODELS
AB Ophthalmology has been one of the early adopters of artificial intelligence (AI) within the medical field. Deep learning (DL), in particular, has garnered significant attention due to the availability of large amounts of data and digitized ocular images. Currently, AI in Ophthalmology is mainly focused on improving disease classification and supporting decision-making when treating ophthalmic diseases such as diabetic retinopathy, age-related macular degeneration (AMD), glaucoma and retinopathy of prematurity (ROP). However, most of the DL systems (DLSs) developed thus far remain in the research stage and only a handful are able to achieve clinical translation. This phenomenon is due to a combination of factors including concerns over security and privacy, poor generalizability, trust and explainability issues, unfavorable end-user perceptions and uncertain economic value. Overcoming this challenge would require a combination approach. Firstly, emerging techniques such as federated learning (FL), generative adversarial networks (GANs), autonomous AI and blockchain will be playing an increasingly critical role to enhance privacy, collaboration and DLS performance. Next, compliance to reporting and regulatory guidelines, such as CONSORT-AI and STARD-AI, will be required to in order to improve transparency, minimize abuse and ensure reproducibility. Thirdly, frameworks will be required to obtain patient consent, perform ethical assessment and evaluate end-user perception. Lastly, proper health economic assessment (HEA) must be performed to provide financial visibility during the early phases of DLS development. This is necessary to manage resources prudently and guide the development of DLS.
C1 [Ng, Wei Yan; Zhang, Shihao; Ong, Charles Jit Teng; Gunasekeran, Dinesh, V; San Lim, Gilbert Yong; Zheng, Feihui; Tan, Shaun Chern Yuan; Tan, Gavin Siew Wei; Rim, Tyler Hyungtaek; Schmetterer, Leopold; Ting, Daniel Shu Wei] Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore.
   [Ng, Wei Yan; Wang, Zhaoran; San Lim, Gilbert Yong; Tan, Gavin Siew Wei; Rim, Tyler Hyungtaek; Schmetterer, Leopold; Ting, Daniel Shu Wei] Natl Univ Singapore, Duke NUS Med Sch, Singapore, Singapore.
   [Gunasekeran, Dinesh, V] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; National University of Singapore
RP Ting, DSW (通讯作者)，Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore.; Ting, DSW (通讯作者)，Natl Univ Singapore, Duke NUS Med Sch, Singapore, Singapore.
EM daniel.ting.s.w@singhealth.com.sg
RI CHENG, FREYA/GOH-0443-2022
OI CHENG, FREYA/0000-0001-9179-3461; Bidwai, Pooja
   Vishal/0000-0002-3077-4395; Schmetterer, Leopold/0000-0002-7189-1707
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NR 191
TC 4
Z9 4
U1 9
U2 31
PU PORTLAND PRESS LTD
PI LONDON
PA 1ST FLR, 10 QUEEN STREET PLACE, LONDON, ENGLAND
SN 0143-5221
EI 1470-8736
J9 CLIN SCI
JI Clin. Sci.
PD OCT
PY 2021
VL 135
IS 20
BP 2357
EP 2376
DI 10.1042/CS20210207
PG 20
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA XA7SF
UT WOS:000720840900002
PM 34661658
DA 2022-11-30
ER

PT J
AU Motschi, AR
   Roberts, PK
   Desissaire, S
   Schranz, M
   Schwarzhans, F
   Bogunovic, H
   Pircher, M
   Hitzenberger, CK
AF Motschi, Alice R.
   Roberts, Philipp K.
   Desissaire, Sylvia
   Schranz, Markus
   Schwarzhans, Florian
   Bogunovic, Hrvoje
   Pircher, Michael
   Hitzenberger, Christoph K.
TI Identification and quantification of fibrotic areas in the human retina
   using polarization-sensitive OCT
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; DEPTH-RESOLVED BIREFRINGENCE; NERVE-FIBER
   LAYER; MACULAR DEGENERATION; IN-VIVO; BIOLOGICAL TISSUE; AXIS
   ORIENTATION; RETARDATION; SEGMENTATION; CONTRAST
AB Subretinal fibrosis is one of the most prevalent causes of blindness in the elderly population, but a true gold standard to objectively diagnose fibrosis is still lacking. Since fibrotic tissue is birefringent, it can be detected by polarization-sensitive optical coherence tomography (PS-OCT). We present a new algorithm to automatically detect, segment, and quantify fibrotic lesions within 3D data sets recorded by PS-OCT. The algorithm first compensates for the birefringence of anterior ocular tissues and then uses the uniformity of the birefringent optic axis as an indicator to identify fibrotic tissue, which is then segmented and quantified. The algorithm was applied to 3D volumes recorded in 57 eyes of 57 patients with neovascular age-related macular degeneration using a spectral domain PS-OCT system. The results of fibrosis detection were compared to the clinical diagnosis based on color fundus photography (CFP), and the precision of fibrotic area measurement was assessed by three repeated measurements in a sub-set of 15 eyes. The average standard deviation of the fibrotic area obtained in eyes with a lesion area 0.7 mm(2) was 15%. Fibrosis detection by CFP and PS-OCT agreed in 48 cases, discrepancies were only observed in cases of lesion area < 0.7 mm(2). These remaining discrepancies are discussed, and a new method to treat ambiguous cases is presented. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License.
C1 [Motschi, Alice R.; Desissaire, Sylvia; Pircher, Michael; Hitzenberger, Christoph K.] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
   [Roberts, Philipp K.; Schranz, Markus] Med Univ Vienna, Dept Ophthalmol & Optometry, Vienna, Austria.
   [Schwarzhans, Florian] Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, Vienna, Austria.
   [Bogunovic, Hrvoje] Med Univ Vienna, Christian Doppler Lab Ophthalm Image Anal, Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna; Medical
   University of Vienna; Medical University of Vienna
RP Motschi, AR (通讯作者)，Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
EM alice.motschi@meduniwien.ac.at
RI Bogunovic, Hrvoje/J-3445-2014
OI Bogunovic, Hrvoje/0000-0002-9168-0894; Michael,
   Pircher/0000-0001-9285-7527; Hitzenberger,
   Christoph/0000-0002-6608-8821; Desissaire, Sylvia/0000-0002-7227-8031
FU Austrian Science Fund [KLI 749]
FX Austrian Science Fund (KLI 749) .
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NR 61
TC 4
Z9 4
U1 1
U2 2
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 JUL 1
PY 2021
VL 12
IS 7
BP 4380
EP 4400
DI 10.1364/BOE.426650
PG 21
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 TE6OV
UT WOS:000670130900004
PM 34457420
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Goerdt, L
   Sauer, L
   Vitale, AS
   Modersitzki, NK
   Fleckenstein, M
   Bernstein, PS
AF Goerdt, Lukas
   Sauer, Lydia
   Vitale, Alexandra S.
   Modersitzki, Natalie K.
   Fleckenstein, Monika
   Bernstein, Paul S.
TI Comparing Fluorescence Lifetime Imaging Ophthalmoscopy in Atrophic Areas
   of Retinal Diseases
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE atrophic retinal diseases; FLIO; fluorescence lifetime imaging;
   geographic atrophy
ID GEOGRAPHIC ATROPHY; FUNDUS AUTOFLUORESCENCE; MACULAR DEGENERATION;
   CHOROIDEREMIA; SENSITIVITY; PROGRESSION; PREVALENCE; PATTERNS; TYPE-2
AB Purpose: Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a non-invasive imaging modality to investigate the human retina. This study compares FLIO lifetimes in different degenerative retinal diseases.
   Methods: Included were eyes with retinal pigment epithelium (RPE) and/or photoreceptor atrophy due to Stargardt disease (n = 66), pattern dystrophy (n = 18), macular telangiectasia type 2 (n= 49), retinitis pigmentosa (n= 28), choroideremia (n= 26), and geographic atrophy (n = 32) in age-related macular degeneration, as well as 37 eyes of 37 age-matched healthy controls. Subjects received Heidelberg Engineering FLIO, autofluorescence intensity, and optical coherence tomography imaging. Amplitude-weighted mean FLIO lifetimes (tau(m)) were calculated and analyzed.
   Results: Retinal FLIO lifetimes show significant differences depending on the disease. Atrophic areas in geographic atrophy and choroideremia showed longest mean FLIO lifetimes. tau(m) values within areas of RPE and outer nuclear layer atrophywere significantly longer than within areas with preserved outer nuclear layer (P < 0.001) or non-atrophic areas (P < 0.001).
   Conclusions: FLIO is able to contribute additional information regarding differences in chronic degenerative retinal diseases. Although it cannot replace conventional autofluorescence imaging, FLIO adds to the knowledge in these diseases andmay help with the correct differentiation between them. This may lead to a more in-depth understanding of the pathomechanisms related to atrophy and types of progression.
   Translational Relevance: Differences between atrophic retinal diseases highlighted by FLIO may indicate separate pathomechanisms leading to atrophy and disease progression.
C1 [Goerdt, Lukas; Sauer, Lydia; Vitale, Alexandra S.; Modersitzki, Natalie K.; Fleckenstein, Monika; Bernstein, Paul S.] Univ Utah, John A Moran Eye Ctr, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
   [Goerdt, Lukas] Univ Bonn, Dept Ophthalmol, Bonn, Germany.
C3 Utah System of Higher Education; University of Utah; University of Bonn
RP Bernstein, PS (通讯作者)，Univ Utah, John A Moran Eye Ctr, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM paul.bernstein@hsc.utah.edu
FU National Institutes of Health [EY11600, EY14800]; LowyMedical Research
   Institute; University of Utah Population Health Research Foundation;
   National Center for Research Resources; National Center for Advancing
   Translational Sciences, National Institutes of Health [UL1TR002538];
   Research to Prevent Blindness
FX The authors thank Heidelberg Engineering for providing the FLIO and for
   their technical assistance; they especially thank Yoshihiko Katayama,
   PhD. The authors thank all co-workers from the John A. Moran Eye Center
   who helped recruit and image patients, as well as Benjamin Brintz, PhD,
   for statistical assistance. Supported by grants fromthe National
   Institutes of Health (EY11600 and EY14800) and by LowyMedical Research
   Institute and Research to Prevent Blindness. This investigation was also
   supported by the University of Utah Population Health Research
   Foundation, with funding obtained in part from the National Center for
   Research Resources and the National Center for Advancing Translational
   Sciences, National Institutes of Health, through Grant UL1TR002538
   (formerly 5UL1TR001067-05, 8UL1TR000105, and UL1RR025764). The funding
   organizations had no role in the design or conduct of this research.
   Heidelberg Engineering provided the FLIO instrument to the University of
   Utah at no cost.
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NR 59
TC 2
Z9 2
U1 0
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 JUN
PY 2021
VL 10
IS 7
AR 11
DI 10.1167/tvst.10.7.11
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA TD3KI
UT WOS:000669229400003
PM 34110387
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Birtel, J
   Gliem, M
   Herrmann, P
   Neuhaus, C
   Holz, FG
   MacLaren, RE
   Scholl, HPN
   Issa, PC
AF Birtel, Johannes
   Gliem, Martin
   Herrmann, Philipp
   Neuhaus, Christine
   Holz, Frank G.
   MacLaren, Robert E.
   Scholl, Hendrik P. N.
   Issa, Peter Charbel
TI North Carolina macular dystrophy shows a particular drusen phenotype and
   atrophy progression
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE genetics; macula; retina; dystrophy
ID QUANTITATIVE FUNDUS AUTOFLUORESCENCE; FAMILY; MCDR1; DEGENERATION;
   DUPLICATION
AB Background/Aim To provide a comprehensive multimodal retinal imaging characterisation of patients with North Carolina macular dystrophy (NCMD). Methods Clinical evaluation and retinal imaging in six families. Results Twenty-one subjects showed phenotypic characteristics of NCMD . Small drusen-like deposits were found in all affected individuals, either tightly grouped in the macula, or surrounding atrophic or fibrotic macular alterations. These small subretinal lesions showed an increased fundus autofluorescence and were associated with only mild irregularities on optical coherence tomography imaging. Similar drusen-like deposits were regularly seen in the peripheral fundus, predominantly temporally and often with a radial distribution. Two patients showed a bilateral chorioretinal atrophy and two had a macular neovascularisation (MNV). Findings from follow-up examinations were available from 11 patients. The retinal phenotype remained overall stable, except for two patients: one patient with atrophy showed a distinct growth of the atrophic lesions on longitudinal AF imaging over a review period of 14 years. One patient with MNV showed a unilateral decline of best-corrected visual acuity. Genetic testing identified the single nucleotide variant chr6:100040987G>C upstream of the PRDM13 gene in all family members with NCMD phenotype. Conclusion Patients with NCMD show a characteristic retinal phenotype and distribution of drusen that differ from drusen in patients with age-related macular degeneration. Although the prognosis of this developmental condition is overall better than for other macular diseases with drusen, patients may be at risk of developing MNV or enlargement of pre-existing atrophy.
C1 [Birtel, Johannes; Gliem, Martin; MacLaren, Robert E.; Issa, Peter Charbel] Oxford Univ Hosp NHS Fdn Trust, Oxford Eye Hosp, Oxford OX3 9DU, England.
   [Birtel, Johannes; Gliem, Martin; MacLaren, Robert E.; Issa, Peter Charbel] Univ Oxford, Nuffield Dept Clin Neurosci, Nuffield Lab Ophthalmol, Oxford, England.
   [Birtel, Johannes; Herrmann, Philipp; Holz, Frank G.] Univ Hosp Bonn, Dept Ophthalmol, Bonn, Germany.
   [Neuhaus, Christine] Bioscientia, Bioscientia Ctr Human Genet, Ingelheim, Germany.
   [Scholl, Hendrik P. N.] Inst Mol & Clin Ophthalmol Basel IOB, Basel, Switzerland.
   [Scholl, Hendrik P. N.] Univ Basel, Dept Ophthalmol, Basel, Switzerland.
C3 Oxford University Hospitals NHS Foundation Trust; University of Oxford;
   University of Bonn; University of Basel
RP Issa, PC (通讯作者)，Oxford Univ Hosp NHS Fdn Trust, Oxford Eye Hosp, Oxford OX3 9DU, England.
EM study-enquiry@outlook.com
RI Charbel Issa, Peter/E-8935-2018
OI Charbel Issa, Peter/0000-0002-0351-6673
FU National Institute for Health Research (NIHR) Oxford Biomedical Research
   Centre (BRC); Dr Werner Jackstadt Foundation, Wuppertal, Germany
   [S0134-10.22]
FX This work was supported by the National Institute for Health Research
   (NIHR) Oxford Biomedical Research Centre (BRC) and by the Dr Werner
   Jackstadt Foundation, Wuppertal, Germany (Grant S0134-10.22 to JB).
CR Birtel J, 2021, KLIN MONATSBL AUGENH, V238, P249, DOI 10.1055/a-1388-7236
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NR 38
TC 3
Z9 3
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 SEP
PY 2022
VL 106
IS 9
BP 1269
EP 1273
DI 10.1136/bjophthalmol-2021-318815
EA MAR 2021
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4D0ZF
UT WOS:000726804400001
PM 33785507
DA 2022-11-30
ER

PT J
AU Pennington, BO
   Bailey, JK
   Faynus, MA
   Hinman, C
   Hee, MN
   Ritts, R
   Nadar, V
   Zhu, DH
   Mitra, D
   Martinez-Camarillo, JC
   Lin, TC
   Thomas, BB
   Hinton, DR
   Humayun, MS
   Lebkowski, J
   Johnson, LV
   Clegg, DO
AF Pennington, Britney O.
   Bailey, Jeffrey K.
   Faynus, Mohamed A.
   Hinman, Cassidy
   Hee, Mitchell N.
   Ritts, Rory
   Nadar, Vignesh
   Zhu, Danhong
   Mitra, Debbie
   Martinez-Camarillo, Juan Carlos
   Lin, Tai-Chi
   Thomas, Biju B.
   Hinton, David R.
   Humayun, Mark S.
   Lebkowski, Jane
   Johnson, Lincoln, V
   Clegg, Dennis O.
TI Xeno-free cryopreservation of adherent retinal pigmented epithelium
   yields viable and functional cells in vitro and in vivo
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; PHAGOCYTOSIS; PARYLENE; DIFFERENTIATION;
   TRANSPLANTATION; VITRIFICATION; MELANOCYTES; PREVALENCE; INTEGRIN
AB Age-related macular degeneration (AMD) is the primary cause of blindness in adults over 60 years of age, and clinical trials are currently assessing the therapeutic potential of retinal pigmented epithelial (RPE) cell monolayers on implantable scaffolds to treat this disease. However, challenges related to the culture, long-term storage, and long-distance transport of such implants currently limit the widespread use of adherent RPE cells as therapeutics. Here we report a xeno-free protocol to cryopreserve a confluent monolayer of clinical-grade, human embryonic stem cell-derived RPE cells on a parylene scaffold (REPS) that yields viable, polarized, and functional RPE cells post-thaw. Thawed cells exhibit >= 95% viability, have morphology, pigmentation, and gene expression characteristic of mature RPE cells, and secrete the neuroprotective protein, pigment epithelium-derived factor (PEDF). Stability under liquid nitrogen (LN2) storage has been confirmed through one year. REPS were administered immediately post-thaw into the subretinal space of a mammalian model, the Royal College of Surgeons (RCS)/nude rat. Implanted REPS were assessed at 30, 60, and 90 days post-implantation, and thawed cells demonstrate survival as an intact monolayer on the parylene scaffold. Furthermore, immunoreactivity for the maturation marker, RPE65, significantly increased over the post-implantation period in vivo, and cells demonstrated functional attributes similar to non-cryopreserved controls. The capacity to cryopreserve adherent cellular therapeutics permits extended storage and stable transport to surgical sites, enabling broad distribution for the treatment of prevalent diseases such as AMD.
C1 [Pennington, Britney O.; Bailey, Jeffrey K.; Faynus, Mohamed A.; Hinman, Cassidy; Clegg, Dennis O.] Univ Calif Santa Barbara, Ctr Stem Cell Biol & Engn, Neurosci Res Inst, NRI,UC Santa Barbara, Biol 2 Bldg 571, Santa Barbara, CA 93106 USA.
   [Pennington, Britney O.; Bailey, Jeffrey K.; Faynus, Mohamed A.; Hinman, Cassidy; Nadar, Vignesh; Lebkowski, Jane; Johnson, Lincoln, V; Clegg, Dennis O.] Regenerat Patch Technol LLC, Portola Valley, CA 94028 USA.
   [Hee, Mitchell N.] Univ Calif Santa Barbara, Coll Creat Studies, Biol, Santa Barbara, CA 93106 USA.
   [Ritts, Rory; Clegg, Dennis O.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
   [Zhu, Danhong; Mitra, Debbie; Martinez-Camarillo, Juan Carlos; Lin, Tai-Chi; Thomas, Biju B.; Hinton, David R.; Humayun, Mark S.] Univ Southern Calif, Keck Sch Med, Usc Roski Eye Inst, Dept Pathol & Ophthalmol, Los Angeles, CA 90007 USA.
   [Humayun, Mark S.] Univ Southern Calif, DRB, Dept Biomed Engn, Los Angeles, CA 90007 USA.
   [Martinez-Camarillo, Juan Carlos; Thomas, Biju B.; Hinton, David R.; Humayun, Mark S.] Univ Southern Calif, USC Dr Allen & Charlotte Ginsburg Inst Biomed The, Los Angeles, CA 90007 USA.
C3 University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara;
   University of Southern California; University of Southern California;
   University of Southern California
RP Pennington, BO (通讯作者)，Univ Calif Santa Barbara, Ctr Stem Cell Biol & Engn, Neurosci Res Inst, NRI,UC Santa Barbara, Biol 2 Bldg 571, Santa Barbara, CA 93106 USA.; Pennington, BO (通讯作者)，Regenerat Patch Technol LLC, Portola Valley, CA 94028 USA.
EM bop@ucsb.edu
FU Garland Initiative for Vision; California Institute for Regenerative
   Medicine (CIRM) [DR1-01444, CL1-00521, TB1-1177, FA1-00616, TG2-01151,
   DR3-07438]; Foundation Fighting Blindness Wynn-Gund Translational
   Research Acceleration Program; Santen
FX This research was funded by Garland Initiative for Vision, the
   California Institute for Regenerative Medicine (CIRM; Grants DR1-01444,
   CL1-00521, TB1-1177, FA1-00616, TG2-01151, and Disease Team 3 Grant
   DR3-07438) and the Foundation Fighting Blindness Wynn-Gund Translational
   Research Acceleration Program. RPT received funding from Santen and
   CIRM.
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NR 51
TC 5
Z9 5
U1 1
U2 3
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAR 18
PY 2021
VL 11
IS 1
AR 6286
DI 10.1038/s41598-021-85631-6
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA TA9UF
UT WOS:000667589500022
PM 33737600
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Shye, M
   Hanna, RM
   Patel, SS
   Tram-Tran, N
   Hou, J
   Mccannel, C
   Khalid, M
   Hanna, M
   Abdelnour, L
   Kurtz, I
AF Shye, Michael
   Hanna, Ramy M.
   Patel, Sapna S.
   Tram-Tran, Ngoc
   Hou, Jean
   Mccannel, Collin
   Khalid, Maham
   Hanna, Mina
   Abdelnour, Lama
   Kurtz, Ira
TI Worsening proteinuria and renal function after intravitreal vascular
   endothelial growth factor blockade for diabetic proliferative
   retinopathy
SO CLINICAL KIDNEY JOURNAL
LA English
DT Review
DE acute kidney injury; aflibercept; bevacizumab; diabetic retinopathy;
   focal and segmental sclerosis; nephrotic syndrome; proteinuria;
   ranibizumab; vascular endothelial growth factor; VEGF depletion
ID SEGMENTAL GLOMERULOSCLEROSIS; MACULAR DEGENERATION; NEPHROTIC SYNDROME;
   FACTOR INHIBITORS; PRESSURE CHANGES; BLOOD-PRESSURE; FACTOR THERAPY;
   BEVACIZUMAB; INJECTION; DISEASE
AB Systemic vascular endothelial growth factor (VEGF) inhibitions can induce worsening hypertension, proteinuria and glomerular diseases of various types. These agents can also be used to treat ophthalmic diseases like proliferative diabetic retinopathy, diabetic macular edema, central retinal vein occlusion and age-related macular degeneration. Recently, pharmacokinetic studies confirmed that these agents are absorbed at levels that result in biologically significant suppression of intravascular VEGF levels. There have now been 23 other cases published that describe renal sequela of intravitreal VEGF blockade, and they unsurprisingly mirror known systemic toxicities of VEGF inhibitors. We present three cases where stable levels of proteinuria and chronic kidney disease worsened after initiation of these agents. Two of our three patients were biopsied. The first patient's biopsy showed diabetic nephropathy and focal and segmental glomerulosclerosis (FSGS) with collapsing features and acute interstitial nephritis (AIN). The second patient's biopsy showed AIN in a background of diabetic glomerulosclerosis. This is the second patient seen by our group, whose biopsy revealed segmental glomerulosclerosis with collapsing features in the setting of intravitreal VEGF blockade. Though FSGS with collapsing features and AIN are not the typical lesions seen with systemic VEGF blockade, they have been reported as rare case reports previously. In addition to reviewing known elements of intravitreal VEGF toxicity, the cases presented encompass renal pathology data supporting that intravitreal VEGF blockade can result in deleterious systemic and renal pathological disorders.
C1 [Shye, Michael; Hanna, Ramy M.; Abdelnour, Lama; Kurtz, Ira] Univ Calif Los Angeles, David Geffen Sch Med, Div Nephrol, Dept Med, Los Angeles, CA 90095 USA.
   [Hanna, Ramy M.; Khalid, Maham] UCI Sch Med, Dept Med, Div Nephrol, Irvine, CA USA.
   [Patel, Sapna S.; Tram-Tran, Ngoc] Long Beach Mem Med Ctr, Dept Med, Div Nephrol, Long Beach, CA USA.
   [Hou, Jean] Cedars Sinai Med Ctr, Dept Pathol, Div Renal Pathol, Los Angeles, CA 90048 USA.
   [Mccannel, Collin] Univ Calif Los Angeles, Dept Ophthalmol, David Geffen Sch Med, Los Angeles, CA USA.
   [Hanna, Mina] Univ Queensland, Sch Med, Ochsner Clin Sch, Ochsner Hlth Syst, New Orleans, LA USA.
   [Kurtz, Ira] Brain Res Ctr, Los Angeles, CA 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; 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; Ochsner Health System; University of Queensland
RP Hanna, RM (通讯作者)，Univ Calif Los Angeles, David Geffen Sch Med, Div Nephrol, Dept Med, Los Angeles, CA 90095 USA.
EM ramyh1@uci.edu
FU National Institutes of Health (NIH) [R01-DK077162]; Allan Smidt
   Charitable Fund; Factor Family Foundation; Ralph Block Family
   Foundation; NIH [R01-DK077162]
FX I.K. is supported in part by funds from the National Institutes of
   Health (NIH) (R01-DK077162), the Allan Smidt Charitable Fund, the Factor
   Family Foundation and the Ralph Block Family Foundation. Sponsorship:
   this work was not sponsored. I.K. is supported in part by funds from the
   NIH (R01-DK077162), the Allan Smidt Charitable Fund, the Factor Family
   Foundation and the Ralph Block Family Foundation.
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NR 62
TC 13
Z9 14
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2048-8505
EI 2048-8513
J9 CLIN KIDNEY J
JI Clin. Kidney J.
PD DEC
PY 2020
VL 13
IS 6
BP 969
EP 980
AR sfaa049
DI 10.1093/ckj/sfaa049
PG 12
WC Urology & Nephrology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Urology & Nephrology
GA PT1SU
UT WOS:000608400700007
PM 33391740
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Lu, YM
   Kim, TH
   Yao, XC
AF Lu, Yiming
   Kim, Tae-Hoon
   Yao, Xincheng
TI Comparative study of wild-type and rd10 mice reveals transient intrinsic
   optical signal response before phosphodiesterase activation in retinal
   photoreceptors
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Intrinsic optical signal; functional imaging; retinal degeneration;
   photoreceptors; rd10; phosphodiesterase deficiency
ID MUTANT MOUSE; PHOTOTRANSDUCTION; DEGENERATION; PHYSIOLOGY
AB Transient intrinsic optical signal (IOS) has been observed in stimulus-evoked retinal photoreceptors. This study is to compare IOS changes in wild-type and retinal degeneration 10 (rd10) mouse retinas, to evaluate the effect of cyclic guanosine monophosphate phosphodiesterase on photoreceptor-IOS. Time-lapse near-infrared light microscopy was employed to monitor the spatiotemporal dynamics of the IOS responses in freshly isolated retinas activated by visible light stimulation. Comparative IOS recordings were conducted at postnatal days 14 (P14) and P16. At P14, intrinsic optical signal magnitudes and spatiotemporal dynamics in wild-type and rd10 retinas were similar, indicating that the phosphodiesterase deficiency in rd10 did not affect the formation of photoreceptor-IOS. At P16, IOS magnitude in rd10 significantly decreased compared to that in wild-type, suggesting the IOS sensitivity to the photoreceptor degeneration in rd10. Our experimental results and theoretical analysis indicate that early disc-based stages of the phototransduction cascade before the activation of phosphodiesterase may contribute to the formation of the photoreceptor-IOS responses; and the IOS can be a sensitive biomarker for objective assessment of retinal function. Impact statement Comparative study of wild-type and rd10 mice was implemented to reveal that transient intrinsic optical signal (IOS) was initiated before the phosphodiesterase activation in stimulus-activated photoreceptors and the IOS magnitude was sensitive to photoreceptor degeneration. The photoreceptor-IOS promises a noninvasive biomarker for objective assessment of age-related macular degeneration, retinitis pigmentosa, and other eye diseases that can produce photoreceptor dysfunctions.
C1 [Lu, Yiming; Kim, Tae-Hoon; Yao, Xincheng] Univ Illinois, Dept Bioengn, Chicago, IL 60607 USA.
   [Yao, Xincheng] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 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
RP Yao, XC (通讯作者)，Univ Illinois, Dept Bioengn, Chicago, IL 60607 USA.; Yao, XC (通讯作者)，Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA.
EM xcy@uic.edu
RI Yao, Xincheng/ABA-1526-2020; Kim, Taehoon/AAS-5818-2020; LU,
   YIMING/AAC-9992-2020
OI LU, YIMING/0000-0002-4895-1484; Kim, Tae-Hoon/0000-0002-4391-4860
FU NIH [R01 EY030101, R01 EY023522, P30 EY001792]; Research to Prevent
   Blindness; Richard and Loan Hill endowment
FX This research was supported in part by NIH grants R01 EY030101, R01
   EY023522, P30 EY001792; by unrestricted grant from Research to Prevent
   Blindness; by Richard and Loan Hill endowment.
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NR 28
TC 7
Z9 7
U1 1
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1535-3702
EI 1535-3699
J9 EXP BIOL MED
JI Exp. Biol. Med.
PD FEB
PY 2020
VL 245
IS 4
SI SI
BP 360
EP 367
AR 1535370219896284
DI 10.1177/1535370219896284
EA DEC 2019
PG 8
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA LA2NJ
UT WOS:000503585300001
PM 31852239
OA Green Published
DA 2022-11-30
ER

PT J
AU Karabulut, M
   Karabulut, S
   Sul, S
   Karalezli, A
AF Karabulut, Mujdat
   Karabulut, Sinem
   Sul, Sabahattin
   Karalezli, Aylin
TI Optic nerve head microvascular changes after phacoemulsification surgery
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Optical coherence tomography angiography; Intraocular pressure
   phacoemulsification; Vessel density
ID OCULAR BLOOD-FLOW; CLEAR CORNEAL PHACOEMULSIFICATION; INCISION
   CATARACT-SURGERY; INTRAOCULAR-PRESSURE; GLAUCOMA; AMPLITUDE; COLOR
AB Background To determine optic nerve head (ONH) microvascular changes detected by optical coherence tomography angiography (OCTA) and intraocular pressure changes (IOPs) after uncomplicated phacoemulsification surgery. Methods The study was designed as a prospective observational study. Twenty-four eyes were included. Eyes with retinal vascular pathology, any type of age-related macular degeneration, IOP more than 21 mmHg, axial length less than 20 mm and more than 24 mm, corneal edema and cataracts that can disrupt images, and history of ocular surgery were excluded. Patients underwent OCTA imaging and IOP measurement preoperatively (baseline) and postoperatively (weeks 1 and 4). Vessel density % (VD) in the total disc, peripapillary, and inside disc were measured. IOP was measured with the applanation tonometer. Comparison of VD and IOP and correlation between VD and IOP change were determined. Results VD was significantly increased in all quadrants in week 4 compared to those in week 1. In terms of VD and IOP, although there was no significant difference between week 1 and baseline, week 4 results were significantly different from baseline (p < 0.05 and p < 0.001, respectively). The IOP was significantly lower in week 4 (14.8 mmHg) than in week 1 (16.0 mmHg) (p < 0.001). There was a significant negative correlation between the inside disc and total VD and IOP at weeks 1 and 4. Conclusion Phacoemulsification surgery can result in a decrease in IOP and an increase in VD of the ONH.
C1 [Karabulut, Mujdat; Karabulut, Sinem; Sul, Sabahattin; Karalezli, Aylin] Mugla Sitki Kocman Univ, Dept Ophthalmol, Med Sch, Mugla, Turkey.
C3 Mugla Sitki Kocman University
RP Karabulut, M (通讯作者)，Mugla Sitki Kocman Univ, Dept Ophthalmol, Med Sch, Mugla, Turkey.
EM mujdatkarabulut@gmail.com
RI Sul, Sabahattin/D-5289-2017; , mujdat/AAH-2911-2021
OI Sul, Sabahattin/0000-0003-4812-7636; , mujdat/0000-0002-7844-5638
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NR 28
TC 1
Z9 2
U1 0
U2 6
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 2019
VL 257
IS 12
BP 2729
EP 2733
DI 10.1007/s00417-019-04473-1
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JO0HP
UT WOS:000497268700018
PM 31529322
DA 2022-11-30
ER

PT J
AU Lu, YM
   Benedetti, J
   Yao, XC
AF Lu, Yiming
   Benedetti, Jacopo
   Yao, Xincheng
TI Light-Induced Length Shrinkage of Rod Photoreceptor Outer Segments
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE photoreceptors; outer segment discs; functional imaging; microscopy
ID ELECTRON-MICROSCOPY; STRUCTURAL-CHANGES; OSMOTIC BEHAVIOR; FROG; RETINA;
   MOUSE; SCATTERING; MORPHOGENESIS; ORGANIZATION; PROTEINS
AB Purpose: This study was designed to verify light-induced outer segment (OS) length shrinkage of rod photoreceptors and to characterize its anatomic source at disc-level resolution.
   Methods: Frog (Rana pipiens) retinas were used for this study. Time-lapse light microscopy of freshly isolated OSs was employed to test transient rod OS changes at 10 ms temporal resolution. Histological light microscopy of dark-and light-adapted retinas was used to confirm light-induced rod OS length changes; and transmission electron microscopy (TEM) was used to quantify light-driven structural perturbation of rod OSs at disc level resolution.
   Results: Time-lapse light microscopy images verified transient length shrinking responses in freshly isolated rod OSs. Histological light microscopy images confirmed reduced rod OS lengths in light-adapted retinas, compared to that of dark-adapted retinas. TEM images disclosed shortened inter-disc distances in light-adapted retinas compared to dark-adapted retinas.
   Conclusions: Light-induced rod OS length shrinkage was confirmed using time-lapse light microscopy of isolated rod OSs and histological light microscopy of dark-and light-adapted retinas. TEM revealed that the rod OS length shrinkage was correlated to the light-driven decrease of the space between individual discs, not the disc thickness itself.
   Translational Relevance: Light-induced transient rod response promises a noninvasive biomarker for early diagnosis of age-related macular degeneration and retinitis pigmentosa, in which the rod photoreceptors are known to be more vulnerable than cone photoreceptors.
C1 [Lu, Yiming; Benedetti, Jacopo; Yao, Xincheng] Univ Illinois, Dept Bioengn, Chicago, IL USA.
   [Yao, Xincheng] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 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
RP Yao, XC (通讯作者)，Univ Illinois, Bioengn & Ophthalmol, Clin Sci North, Suite W103,Room 164D,820 South Wood St, Chicago, IL 60612 USA.
EM xcy@uic.edu
RI LU, YIMING/AAC-9992-2020; Yao, Xincheng/ABA-1526-2020
OI LU, YIMING/0000-0002-4895-1484; 
FU NIH [R01 EY023522, R01 EY024628, P30 EY001792]; Research to Prevent
   Blindness; Richard and Loan Hill endowment; NATIONAL EYE INSTITUTE
   [P30EY001792, R01EY024628, R01EY023522] Funding Source: NIH RePORTER
FX Supported by NIH grants R01 EY023522, R01 EY024628, and P30 EY001792; by
   an unrestricted grant from Research to Prevent Blindness; and by Richard
   and Loan Hill endowment.
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NR 40
TC 15
Z9 15
U1 0
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 DEC
PY 2018
VL 7
IS 6
AR 29
DI 10.1167/tvst.7.6.29
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HF7VA
UT WOS:000454448100001
PM 30619649
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Jiang, SB
   Franco, YL
   Zhou, Y
   Chen, JJ
AF Jiang, Sibo
   Franco, Yesenia L.
   Zhou, Yan
   Chen, Jianjun
TI Nanotechnology in retinal drug delivery
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE nanotechnology; nanoparticle; drug delivery; retina; age-related macular
   degeneration; diabetic retinopathy
ID INTRAVITREAL INJECTION; OCULAR DELIVERY; NANOPARTICLES; HYDROGELS; EYE;
   RELEASE; BEVACIZUMAB; CARBOPLATIN; NANOSPHERES; SYSTEMS
AB Retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy (DR) are the leading causes of blindness in adults over the age of 50 years in the US. While most of those conditions do not have a cure, currently available treatment options attempt to prevent further vision loss. For many ophthalmic drugs, an efficient delivery system to provide maximum therapeutic efficacy and promote patient compliance remains an unmet medical need. An exploration of literature via PubMed spanning from 2007 to 2017 was conducted to identify studies that have evaluated nanotechnology as platforms for delivering therapeutic agents to the posterior segment of the eye where the retina is located. Until now, four routes that have been utilized for retinal drug delivery are the intravitreal, periocular, subretinal, and systemic routes. Intravitreal injections are now widely used in clinical practice due to their ability to directly target the back of the eye but are highly invasive procedures that may cause several complications, particularly with repeated uses over a short timespan. Nanotechnology shows great promise to revolutionize retinal drug delivery, offering many advantages such as a targeted delivery system towards the specific site of the retina as well as sustained delivery of therapeutic agents. In this review, specific eye anatomy and constraints on ocular drug administration are illustrated. Further, we list and highlight several examples of nanosystems, such as hydrogels, liposomes, dendrimers, and micelles, used via different drug delivery routes to treat various retinal diseases.
C1 [Jiang, Sibo; Franco, Yesenia L.] Univ Florida, Dept Pharmaceut, Orlando, FL 32827 USA.
   [Zhou, Yan] Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA.
   [Chen, Jianjun] Southern Med Univ, Guangdong Prov Key Lab New Drug Screening, Sch Pharmaceut Sci, Guangzhou 510515, Guangdong, Peoples R China.
C3 State University System of Florida; University of Florida; University of
   Minnesota System; University of Minnesota Twin Cities; Southern Medical
   University - China
RP Chen, JJ (通讯作者)，Southern Med Univ, Guangdong Prov Key Lab New Drug Screening, Sch Pharmaceut Sci, Guangzhou 510515, Guangdong, Peoples R China.
EM jchen21@smu.edu.cn
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NR 50
TC 37
Z9 38
U1 3
U2 30
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 1038
EP 1044
DI 10.18240/ijo.2018.06.23
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GM0BY
UT WOS:000437711600023
PM 29977820
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Zarbin, MA
AF Zarbin, Marco A.
TI Anti-VEGF Agents and the Risk of Arteriothrombotic Events
SO ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE anti-VEGF agents; arteriothrombotic events; plausibility
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC MACULAR EDEMA; INTRAVITREAL
   INJECTION; CARDIOVASCULAR-DISEASE; PLASMA-LEVELS; DEGENERATION;
   RANIBIZUMAB; AFLIBERCEPT; STROKE; METAANALYSIS
AB Blockade of vascular endothelial growth factor (VEGF) signaling, whether via sequestration of free VEGF or via inhibition of the tyrosine kinases activated by VEGF, is associated with decreased nitric oxide (NO) and prostaglandin-I2 (PG-I2) production along with vascular endothelial cell death. Systemic administration of drugs that block VEGF signaling (eg, for cancer treatment) is associated with systemic complications such as hypertension and thrombosis. Evidence regarding the risk of systemic serious adverse events after intravitreal injection of anti-VEGF agents in patients with diabetic macular edema or neovascular age-related macular degeneration is inconsistent, in part because of study design limitations (eg, bias of ascertainment through strict enrollment criteria and/ or inadequate power to identify the risk of low frequency events). Studies involving patients at high risk of arteriothrombotic events (eg, patients with diabetic macular edema) who have high exposure to intravitreal anti-VEGF therapy (eg, monthly aflibercept or ranibizumab injection) demonstrate an increased risk of all-cause mortality compared with randomized controls. The pharmacokinetics of anti-VEGF drug clearance from the systemic circulation and the documented sustained reduction in free plasma VEGF levels after intravitreal aflibercept and bevacizumab injection are consistent with these findings. Although the frequency of systemic serious adverse events after intravitreal anti-VEGF therapy is low, some patients may be at higher risk (eg, those with recent stroke or multiple strokes), and physicians may wish to take special measures with these patients to minimize the risk of systemic complications.
C1 [Zarbin, Marco A.] Rutgers New Jersey Med Sch, Inst Ophthalmol & Visual Sci, Newark, NJ USA.
C3 Rutgers State University New Brunswick; Rutgers State University Medical
   Center
RP Zarbin, MA (通讯作者)，Rutgers State Univ, Inst Ophthalmol & Visual Sci, Rutgers New Jersey Med Sch, 90 Bergen St, Newark, NJ 07103 USA.
EM zarbin@earthlink.net
OI Zarbin, Marco/0000-0002-7811-7132
FU New Jersey Lions Eye Research Foundation; Eng Family Fund for Excellence
   in Ophthalmology; Joseph J. and Marguerite DiSepio Retina Research Fund
FX Supported in part by the New Jersey Lions Eye Research Foundation, the
   Eng Family Fund for Excellence in Ophthalmology, and the Joseph J. and
   Marguerite DiSepio Retina Research Fund.
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NR 31
TC 30
Z9 30
U1 1
U2 5
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 JAN-FEB
PY 2018
VL 7
IS 1
SI SI
BP 63
EP 67
DI 10.22608/APO.2017495
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GA2CM
UT WOS:000428124300011
PM 29405046
DA 2022-11-30
ER

PT J
AU Pan, JS
   Li, JR
   Chen, ZD
   Mangiaracina, EA
   Connell, CS
   Wu, HY
   Wang, XM
   Bingham, GP
   Hassan, SE
AF Pan, Jing Samantha
   Li, Jingrong
   Chen, Zidong
   Mangiaracina, Emily A.
   Connell, Christopher S.
   Wu, Hongyuan
   Wang, Xiaoye Michael
   Bingham, Geoffrey P.
   Hassan, Shirin E.
TI Motion-generated optical information allows event perception despite
   blurry vision in AMD and amblyopic patients
SO JOURNAL OF VISION
LA English
DT Article
DE blurry vision; age-related macular degeneration; amblyopia; event
   perception; optic flow; image structure
ID CONTRAST-SENSITIVITY; FLOW; DYNAMICS; DESIGN; CHARTS
AB Events consist of objects in motion. When objects move, their opaque surfaces reflect light and produce both static image structure and dynamic optic flow. The static and dynamic optical information co-specify events. Patients with age-related macular degeneration (AMD) and amblyopia cannot identify static objects because of weakened image structure. However, optic flow is detectable despite blurry vision because visual motion measurement uses low spatial frequencies. When motion ceases, image structure persists and might preserve properties specified by optic flow. We tested whether optic flow and image structure interact to allow event perception with poor static vision. AMD (Experiment 1), amblyopic (Experiments 2 and 3), and normally sighted observers identified common events from either blurry (Experiments 1 and 2) or clear images (Experiment 3), when either single image frames were presented, a sequence of frames was presented with motion masks, or a sequence of frames was presented with detectable motion. Results showed that with static images, but no motion, events were not perceived well by participants other than controls in Experiment 3. However, with detectable motion, events were perceived. Immediately following this and again after five days, participants were able to identify events from the original static images. So, when image structure information is weak, optic flow compensates for it and enables event perception. Furthermore, weakened static image structure information nevertheless preserves information that was once available in optic flow. The combination is powerful and allows events to be perceived accurately and stably despite blurry vision.
C1 [Pan, Jing Samantha; Wu, Hongyuan] Sun Yat Sen Univ, Dept Psychol, Guangzhou, Guangdong, Peoples R China.
   [Li, Jingrong; Chen, Zidong] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China.
   [Mangiaracina, Emily A.; Connell, Christopher S.; Hassan, Shirin E.] Indiana Univ, Sch Optometry, Bloomington, IN USA.
   [Wang, Xiaoye Michael; Bingham, Geoffrey P.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA.
C3 Sun Yat Sen University; Sun Yat Sen University; Indiana University
   System; Indiana University Bloomington; Indiana University System;
   Indiana University Bloomington
RP Pan, JS (通讯作者)，Sun Yat Sen Univ, Dept Psychol, Guangzhou, Guangdong, Peoples R China.
EM panj27@mail.sysu.edu.cn
OI Wang, Xiaoye/0000-0003-1272-368X
FU National Natural Science Foundation of China [31571116]; Sun Yat-sen
   University [16wkpy29]
FX This project was funded by the National Natural Science Foundation of
   China (Grant 31571116) and Sun Yat-sen University (Grant 16wkpy29),
   awarded to the first author. The funding agencies had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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   UEBERSAX JS, 1987, PSYCHOL BULL, V101, P140, DOI 10.1037/0033-2909.101.1.140
   West SK, 2002, ARCH OPHTHALMOL-CHIC, V120, P774
NR 35
TC 2
Z9 3
U1 1
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 1534-7362
J9 J VISION
JI J. Vision
PD OCT
PY 2017
VL 17
IS 12
AR 13
DI 10.1167/17.12.13
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA FO8IK
UT WOS:000417128900013
PM 29067401
OA gold
DA 2022-11-30
ER

PT J
AU Popovic, M
   Chaudhary, V
   McKay, BR
   Moinul, P
   Mohaghagh, M
   Beattie, A
   Fava, M
   Eino, D
   Mann, K
   Kobetz, L
   Barbosa, J
AF Popovic, Marko
   Chaudhary, Varun
   McKay, Bryon R.
   Moinul, Prima
   Mohaghagh, Mohammad
   Beattie, Anne
   Fava, Mark
   Eino, Dalia
   Mann, Keith
   Kobetz, Lawrence
   Barbosa, Joshua
TI Discrepancies in physician patient agreement in reporting ocular history
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
ID GLAUCOMA PATIENTS
AB Objective: The purpose of this study was to investigate the extent of agreement between physicians and patients in reporting ocular history and to determine whether there are any predictive factors for physician patient consensus.
   Design: Retrospective chart review.
   Participants: Between June and September 2014, adult patients undergoing cataract surgery were recruited for the study.
   Methods: Before surgery, patient demographics and self-reported ocular history were extracted from a prospectively collected database. Medical charts were retrospectively examined to retrieve physician-reported ocular history.
   Results: One hundred and thirty-eight patients participated. Mean cohort log MAR visual acuity was 0.46 +/- 0.34 (Snellen equivalent of approximately 20/60) and mean age was 74.1 +/- 8.3 years. For glaucoma, Cohen's kappa revealed a moderate-to-good concordance between physicians and patients (kappa = 0.604), whereas a poor-to-fairlevel of agreement existed in reporting maculopathy, such as age-related macular degeneration and macular holes (kappa = 0.254). The logistic regression model revealed that preoperative visual acuity (p = 0.223), sex (p = 0.736), age (p = 0.910), and education (p = 0.738) were not significant predictors of physician patient agreement.
   Conclusions: The accuracy of patient-reported ocular history varies by pathology. Self-reported glaucoma history is consistent between patients and physicians; however, patients under-report the diagnosis of maculopathy. Age, sex, and level of education do not appear to influence patient-reported accuracy of ocular comorbidities.
C1 McMaster Univ, Hamilton Reg Eye Inst, Dept Surg, Div Ophthalmol, Hamilton, ON, Canada.
   McMaster Univ, Dept Surg, St Josephs Hosp, Eye Res Unit,Hamilton Reg Eye Inst, Hamilton, ON, Canada.
C3 McMaster University; McGill University; McMaster University
RP Chaudhary, V (通讯作者)，Hamilton Reg Eye Inst, Dept Surg, Div Ophthalmol, 2757 King St East, Hamilton, ON L8G 5E4, Canada.
EM vchaudh@mcmaster.ca
RI Chaudhary, Varun/AAQ-2371-2021
OI Chaudhary, Varun/0000-0002-9988-4146; Popovic, Marko/0000-0002-0370-5968
CR Caterino JM, 2013, AM J EMERG MED, V31, P1397, DOI 10.1016/j.ajem.2013.06.014
   Chaudhary V, CAN J OPHTH IN PRESS
   Eze-Nliam C, 2012, BMC HEALTH SERV RES, V12, DOI 10.1186/1472-6963-12-78
   Freedman SF, 2003, AM J OPHTHALMOL, V136, P640, DOI 10.1016/S0002-9394(03)00334-9
   Grodum K, 2002, ACTA OPHTHALMOL SCAN, V80, P627, DOI 10.1034/j.1600-0420.2002.800613.x
   Khan IJ, 2014, OPHTHALMOLOGY, V121, P492, DOI 10.1016/j.ophtha.2013.09.033
   Mbadugha CA, 2014, SCI REP-UK, V4, DOI 10.1038/srep07585
NR 7
TC 6
Z9 6
U1 0
U2 0
PU CANADIAN OPHTHAL SOC
PI OTTAWA
PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA
SN 0008-4182
EI 1715-3360
J9 CAN J OPHTHALMOL
JI Can. J. Opthalmol.-J. Can. Opthalmol.
PD OCT
PY 2016
VL 51
IS 5
BP 378
EP 381
DI 10.1016/j.jcjo.2016.03.011
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EA9GQ
UT WOS:000386950900024
PM 27769330
DA 2022-11-30
ER

PT J
AU Waizel, M
   Rickmann, A
   Blanke, BR
   Wolf, K
   Kazerounian, S
   Szurman, P
AF Waizel, Maria
   Rickmann, Annekatrin
   Blanke, Bjoern R.
   Wolf, Katharina
   Kazerounian, Sara
   Szurman, Peter
TI Response to bevacizumab after treatment with aflibercept in eyes with
   neovascular AMD
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Aflibercept; Bevacizumab; Ranibizumab; Vascular endothelial growth
   factor; Vascular endothelial growth factor A; VEGF switch
ID ANTI-VEGF THERAPY; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION;
   INTRAVITREAL AFLIBERCEPT; RANIBIZUMAB; TACHYPHYLAXIS; SWITCH
AB Purpose: To study the visual outcome and change in central macular thickness (CMT) in patients with neovascular age-related macular degeneration (AMD) who were previously treated with aflibercept (VEGF Trap-Eye, Eylea) and were subsequently switched to bevacizumab (Avastin).
   Methods: In this observational analysis, 19 eyes initially treated with at least 3 injections of bevacizumab after initial treatment with at least 3 injections of aflibercept are reported. Outcome measures were Snellen visual acuity (best-corrected visual acuity (BCVA) and CMT measured by spectral-domain optical coherence tomography.
   Results: A total of 19 eyes initially treated with 6.5 +/- 2.8 intravitreal injections of aflibercept were switched to 5.4 +/- 3.2 injections of bevacizumab. Median BCVA decreased from 20/94 to 20/113 after aflibercept and increased slightly to 20/101 after bevacizumab (p = 0.84, Friedman test). Of all 19 eyes, 36.8% achieved gain in visual acuity of more than 1 line and 21.1% of more than 3 lines. The CMT decreased slightly from 433 +/- 229 mu m at baseline to 367 +/- 198 mu m after aflibercept treatment (p = 0.18, Wilcoxon test) and decreased statistically significantly to 335 +/- 184 mu m after bevacizumab treatment (p = 0.0065, Wilcoxon test).
   Conclusions: Switching from aflibercept to bevacizumab treatment has an equivalent anatomical effect in eyes with neovascular AMD as switching from bevacizumab to aflibercept. Therefore, switching back to bevacizumab might represent a reasonable therapy strategy to overcome tachyphylaxis during long-term monotherapy with aflibercept.
C1 [Waizel, Maria; Kazerounian, Sara] Univ Eye Hosp Basel, Ctr Ophthalmol, Basel, Switzerland.
   [Waizel, Maria; Rickmann, Annekatrin; Wolf, Katharina; Kazerounian, Sara; Szurman, Peter] Knappschaft Hosp Saar, Knappschaft Eye Clin Sulzbach, Sulzbach, Germany.
   [Blanke, Bjoern R.; Szurman, Peter] Univ Eye Clin Tuebingen, Ctr Ophthalmol, Tubingen, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital
RP Waizel, M (通讯作者)，Univ Eye Hosp Basel, Switzerland Mittlere Str 91, Basel, Switzerland.
EM maria.waizel@usb.ch
OI Waizel, Maria/0000-0002-6588-4842
CR Bakall B, 2013, AM J OPHTHALMOL, V156, P15, DOI 10.1016/j.ajo.2013.02.017
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NR 12
TC 8
Z9 10
U1 0
U2 1
PU WICHTIG PUBLISHING
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 1120-6721
EI 1724-6016
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD SEP-OCT
PY 2016
VL 26
IS 5
BP 469
EP 472
DI 10.5301/ejo.5000781
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EK1MB
UT WOS:000393688500026
PM 27079204
DA 2022-11-30
ER

PT J
AU Fei, P
   Zaitoun, I
   Farnoodian, M
   Fisk, DL
   Wang, SJ
   Sorenson, CM
   Sheibani, N
AF Fei, Ping
   Zaitoun, Ismail
   Farnoodian, Mitra
   Fisk, Debra L.
   Wang, Shoujian
   Sorenson, Christine M.
   Sheibani, Nader
TI Expression of Thrombospondin-1 Modulates the Angioinflammatory Phenotype
   of Choroidal Endothelial Cells
SO PLOS ONE
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; RETINAL VASCULAR DEVELOPMENT; GROWTH-FACTOR;
   VE-CADHERIN; IN-VITRO; ANGIOGENESIS; ENDOGLIN; GENE; NEOVASCULARIZATION;
   HETEROGENEITY
AB The choroidal circulation plays a central role in maintaining the health of outer retina and photoreceptor function. Alterations in this circulation contribute to pathogenesis of many eye diseases including exudative age-related macular degeneration. Unfortunately, very little is known about the choroidal circulation and its molecular and cellular regulation. This has been further hampered by the lack of methods for routine culturing of choroidal endothelial cells (ChEC), especially from wild type and transgenic mice. Here we describe a method for isolation and culturing of mouse ChEC. We show that expression of thrombospondin-1 (TSP1), an endogenous inhibitor of angiogenesis and inflammation, has a significant impact on phenotype of ChEC. ChEC from TSP1-deficient (TSP1-/-) mice were less proliferative and more apoptotic, less migratory and less adherent, and failed to undergo capillary morphogenesis in Matrigel. However, re-expression of TSP1 was sufficient to restore TSP1-/- ChEC migration and capillary morphogenesis. TSP1-/- ChEC expressed increased levels of TSP2, phosphorylated endothelial nitric oxide synthase (NOS) and inducible NOS (iNOS), a marker of inflammation, which was associated with significantly higher level of NO and oxidative stress in these cells. Wild type and TSP1-/- ChEC produced similar levels of VEGF, although TSP1-/- ChEC exhibited increased levels of VEGF-R1 and pSTAT3. Other signaling pathways including Src, Akt, and MAPKs were not dramatically affected by the lack of TSP1. Together our results demonstrate an important autocrine role for TSP1 in regulation of ChEC phenotype.
C1 [Fei, Ping; Zaitoun, Ismail; Farnoodian, Mitra; Fisk, Debra L.; Wang, Shoujian; Sheibani, Nader] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA.
   [Sorenson, Christine M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI USA.
   [Sorenson, Christine M.; Sheibani, Nader] Univ Wisconsin, Sch Med & Publ Hlth, McPherson Eye Res Inst, Madison, WI USA.
   [Sheibani, Nader] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biomed Engn, Madison, WI 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;
   University of Wisconsin System; University of Wisconsin Madison
RP Sheibani, N (通讯作者)，Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA.
EM nsheibanikar@wisc.edu
RI Sheibani, Nader/AAG-2379-2020
OI Sheibani, Nader/0000-0003-2723-9217
FU UW Paul P. Carbone Cancer Center Support Grant from the National
   Institutes of Health [EY023024, EY022883, P30 EY016665, P30 CA014520];
   Research to Prevent Blindness; American Diabetes Association
   [1-10-BS-160]; Retina Research Foundation; NATIONAL CANCER INSTITUTE
   [P30CA014520] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [P30EY016665, R21EY023024, R24EY022883] Funding Source: NIH RePORTER
FX This work was supported by grants EY023024, EY022883, P30 EY016665 Core
   grant, and P30 CA014520 UW Paul P. Carbone Cancer Center Support Grant
   from the National Institutes of Health and an unrestricted departmental
   award from Research to Prevent Blindness. NS is a recipient of a
   Research Award from American Diabetes Association, 1-10-BS-160 and
   Retina Research 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 63
TC 21
Z9 21
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 DEC 30
PY 2014
VL 9
IS 12
AR e116423
DI 10.1371/journal.pone.0116423
PG 28
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AX6YH
UT WOS:000347063500083
PM 25548916
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zhao, ZY
   Xu, P
   Jie, ZL
   Zuo, YQ
   Yu, B
   Soong, L
   Sun, JR
   Chen, Y
   Cai, JY
AF Zhao, Zhenyang
   Xu, Pei
   Jie, Zuliang
   Zuo, Yiqin
   Yu, Bo
   Soong, Lynn
   Sun, Jiaren
   Chen, Yan
   Cai, Jiyang
TI gamma delta T Cells as a Major Source of IL-17 Production During
   Age-Dependent RPE Degeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; IL-17; inflammation; T lymphocyte
ID SUBRETINAL DRUSENOID DEPOSITS; MACULAR DEGENERATION; MICROGLIAL
   ACTIVATION; APOLIPOPROTEIN-E; RETICULAR PSEUDODRUSEN; HUMAN RETINA;
   PIVOTAL ROLE; MOUSE MODEL; ACCUMULATION; INFLAMMATION
AB PURPOSE. Chronic inflammation is a key factor contributing to the progression of age-related macular degeneration (AMD). The goals of the current study were to develop an improved mouse model with retinal pathologic features similar to those of AMD and to characterize the immunoreactive cells in the outer retina and choroid during degeneration of the retinal pigment epithelium (RPE).
   METHODS. Mice deficient in nuclear erythroid 2-related factor 2 (Nrf2) at 12 months of age were fed a high-fat, cholesterol-rich diet for up to 16 weeks. Ocular phenotype was monitored by optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) in live animals, and was further validated by retinal histopathology. Immunofluorescence staining of either cryosections or RPE flat mounts was used to define immunoreactive cells. Flow cytometry analyses were further performed to define the subsets of intraocular T lymphocytes.
   RESULTS. After 16 weeks on a high-fat (HF) diet, 58% of the eyes from Nrf2(-/-) mice had progression of retinal lesions. Major histocompatibility complex class II (MHC II)-positive microglia, FoxP3(+) regulatory T cells (Tregs), and CD3(+) IL-17-producing T cells were detected in either the retina or sub-RPE space. Flow cytometry analyses further revealed that most of the IL-17-producing cells were CD3(+) CD4(-) TCR gamma delta(+) cells.
   CONCLUSIONS. The results suggest that the T cell-mediated immune responses played important roles in controlling the progression of AMD-like phenotype in Nrf2-deficient mice.
C1 [Zhao, Zhenyang; Xu, Pei; Zuo, Yiqin; Yu, Bo; Chen, Yan; Cai, Jiyang] Univ Texas Med Branch, Dept Ophthalmol & Visual Sci, 301 Univ Blvd, Galveston, TX 77555 USA.
   [Jie, Zuliang; Soong, Lynn; Sun, Jiaren] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
   [Cai, Jiyang] Univ Texas Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77555 USA.
C3 University of Texas System; University of Texas Medical Branch
   Galveston; University of Texas System; University of Texas Medical
   Branch Galveston; University of Texas System; University of Texas
   Medical Branch Galveston
RP Cai, JY (通讯作者)，Univ Texas Med Branch, Dept Ophthalmol & Visual Sci, 301 Univ Blvd, Galveston, TX 77555 USA.
EM jicai@utmb.edu
RI Zhao, Zhenyang/N-3321-2015; Xu, Pei/B-1680-2016
OI Zhao, Zhenyang/0000-0002-1701-3751; Xu, Pei/0000-0002-9480-8021
FU National Institutes of Health [EY 021937, EY 019706, AI 109100];
   BrightFocus Foundation; International Retina Research Foundation; Ted
   Nash Long Life Foundation; NATIONAL EYE INSTITUTE [R00EY019706,
   R01EY021937] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY
   AND INFECTIOUS DISEASES [R21AI109100] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health Grants EY 021937, EY 019706,
   and AI 109100; BrightFocus Foundation; International Retina Research
   Foundation; and Ted Nash Long Life Foundation.
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NR 80
TC 28
Z9 29
U1 0
U2 13
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 OCT
PY 2014
VL 55
IS 10
DI 10.1167/iovs.14-15166
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AT1ZS
UT WOS:000344730500004
PM 25212781
OA Green Published
DA 2022-11-30
ER

PT J
AU Croze, RH
   Buchholz, DE
   Radeke, MJ
   Thi, WJ
   Hu, QR
   Coffey, PJ
   Clegg, DO
AF Croze, Roxanne H.
   Buchholz, David E.
   Radeke, Monte J.
   Thi, William J.
   Hu, Qirui
   Coffey, Peter J.
   Clegg, Dennis O.
TI ROCK Inhibition Extends Passage of Pluripotent Stem Cell-Derived Retinal
   Pigmented Epithelium
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE Embryonic stem cells; Retinal pigmented epithelium; Cellular therapy;
   Cell culture; Cell proliferation
ID RHO KINASE INHIBITOR; MESENCHYMAL TRANSITION; MACULAR DEGENERATION;
   DIRECTED DIFFERENTIATION; SMOOTH-MUSCLE; PROLIFERATION; PROTEIN; RPE;
   SURVIVAL; PATHWAY
AB Human embryonic stem cells (hESCs) offer a potentially unlimited supply of cells for emerging cell-based therapies. Unfortunately, the process of deriving distinct cell types can be time consuming and expensive. In the developed world, age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with more than 7.2 million people afflicted in the U.S. alone. Both hESC-derived retinal pigmented epithelium (hESC-RPE) and induced pluripotent stem cell-derived RPE (iPSC-RPE) are being developed for AMD therapies by multiple groups, but their potential for expansion in culture is limited. To attempt to overcome this passage limitation, we examined the involvement of Rho-associated, coiled-coil protein kinase (ROCK) in hESC-RPE and iPSC-RPE culture. We report that inhibiting ROCK1/2 with Y-27632 allows extended passage of hESC-RPE and iPSC-RPE. Microarray analysis suggests that ROCK inhibition could be suppressing an epithelial-to-mesenchymal transition through various pathways. These include inhibition of key ligands of the transforming growth factor-beta pathway (TGFB1 and GDF6) and Wnt signaling. Two important processes are affected, allowing for an increase in hESC-RPE expansion. First, ROCK inhibition promotes proliferation by inducing multiple components that are involved in cell cycle progression. Second, ROCK inhibition affects many pathways that could be converging to suppress RPE-to-mesenchymal transition. This allows hESC-RPE to remain functional for an extended but finite period in culture.
C1 [Croze, Roxanne H.; Buchholz, David E.; Thi, William J.; Hu, Qirui; Clegg, Dennis O.] Univ Calif Santa Barbara, Ctr Stem Cell Biol & Engn, Santa Barbara, CA 93106 USA.
   [Croze, Roxanne H.; Buchholz, David E.; Radeke, Monte J.; Thi, William J.; Hu, Qirui; Coffey, Peter J.; Clegg, Dennis O.] Univ Calif Santa Barbara, Ctr Study Macular Degenerat, Santa Barbara, CA 93106 USA.
   [Croze, Roxanne H.; Buchholz, David E.; Radeke, Monte J.; Thi, William J.; Hu, Qirui; Coffey, Peter J.; Clegg, Dennis O.] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
   [Croze, Roxanne H.; Buchholz, David E.; Radeke, Monte J.; Thi, William J.; Hu, Qirui; Coffey, Peter J.; Clegg, Dennis O.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara
RP Clegg, DO (通讯作者)，Univ Calif Santa Barbara, Ctr Stem Cell Biol & Engn, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
EM clegg@lifesci.ucsb.edu
OI Coffey, Peter/0000-0002-5427-2939
FU Garland Initiative for Vision; California Institute for Regenerative
   Medicine [DR1-0144, LA1-02086, DR1-01444, CL1-00521, TG2-01151]; Fight
   for Sight; Foundation Fighting Blindness Wynn-Gund Translational
   Research Acceleration Program; University of California Santa Barbara
   Institute for Collaborative Biotechnologies from the U.S. Army Research
   Office [W911NF-09-0001]; Bright Focus Foundation [M2011064]; Major
   Facilities Grant [FA1-00616]
FX This work was supported by the Garland Initiative for Vision, Grant
   DR1-0144 from the California Institute for Regenerative Medicine, Fight
   for Sight, The Foundation Fighting Blindness Wynn-Gund Translational
   Research Acceleration Program, the University of California Santa
   Barbara Institute for Collaborative Biotechnologies through Grant
   W911NF-09-0001 from the U.S. Army Research Office, the Bright Focus
   Foundation (M2011064, M.J.R.) and the California Institute for
   Regenerative Medicine (LA1-02086 [P.J.C.], DR1-01444, CL1-00521,
   TG2-01151 (D.O.C.), and Major Facilities Grant FA1-00616. R.H.C. is a
   fellow of the California Institute for Regenerative Medicine. The
   content of the information does not necessarily reflect the position or
   the policy of the government, and no official endorsement should be
   inferred. We thank Carolyn Radeke for technical support of the
   microarray experiments and Lincoln Johnson, Dean Bok, James Thomson, and
   David Gamm for their generous gifts of fetal and induced pluripotent
   stem cells.
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NR 75
TC 51
Z9 52
U1 1
U2 23
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD SEP
PY 2014
VL 3
IS 9
BP 1066
EP 1078
DI 10.5966/sctm.2014-0079
PG 13
WC Cell & Tissue Engineering
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA AP6LJ
UT WOS:000342189000023
PM 25069775
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Zhao, LL
   Wang, CG
   Song, DL
   Li, YF
   Song, Y
   Su, GF
   Dunaief, JL
AF Zhao, Liangliang
   Wang, Chenguang
   Song, Delu
   Li, Yafeng
   Song, Ying
   Su, Guanfang
   Dunaief, Joshua L.
TI Systemic Administration of the Antioxidant/Iron Chelator alpha-Lipoic
   Acid Protects Against Light-Induced Photoreceptor Degeneration in the
   Mouse Retina
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE lipoic acid; oxidative stress; light damage; retinal degeneration
ID EXPERIMENTAL DIABETIC-RETINOPATHY; PIGMENT EPITHELIAL-CELLS; MACULAR
   DEGENERATION; OXIDATIVE STRESS; DEFERIPRONE PROTECTS; RAT RETINA; IRON;
   MICE; COMPLEMENT; MEMORY
AB PURPOSE. Oxidative stress and inflammation have key roles in the light damage (LD) model of retinal degeneration as well as in age-related macular degeneration (AMD). We sought to determine if lipoic acid (LA), an antioxidant and iron chelator, protects the retina against LD.
   METHODS. Balb/c mice were treated with LA or control saline via intraperitoneal injection, and then were placed in constant cool white light-emitting diode (LED) light (10,000 lux) for 4 hours. Retinas were evaluated at several time points after LD. Photoreceptor apoptosis was assessed using the TUNEL assay. Retinal function was analyzed via electroretinography (ERG). Retinal degeneration was assessed after LD by optical coherence tomography (OCT), TUNEL analysis, and histology. The mRNAs of several oxidative stress, inflammation, and iron-related genes were quantified by quantitative PCR (qPCR).
   RESULTS. The LD resulted in substantial photoreceptor-specific cell death. Dosing with LA protected photoreceptors, decreasing the numbers of TUNEL-positive photoreceptors and increasing the number of surviving photoreceptors. The retinal mRNA levels of genes indicating oxidative stress, inflammation, and iron accumulation were lower following LD in mice treated with LA than in control mice. The ERG analysis demonstrated functional protection by LA.
   CONCLUSIONS. Systemic LA is protective against light-induced retinal degeneration. Since this agent already has proven protective in other retinal degeneration models, and is safe and protective against diabetic neuropathy in patients, it is worthy of consideration for a human clinical trial against retinal degeneration or AMD.
C1 [Zhao, Liangliang; Wang, Chenguang; Su, Guanfang] Jilin Univ, Hosp 2, Dept Ophthalmol, Changchun, Jilin, Peoples R China.
   [Zhao, Liangliang; Wang, Chenguang; Song, Delu; Li, Yafeng; Song, Ying; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
C3 Jilin University; University of Pennsylvania; Pennsylvania Medicine
RP Dunaief, JL (通讯作者)，305 Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@upenn.edu
FU Pennsylvania Lions Eye Resarch and Sight Conservation Foundation;
   National Institutes of Health (NIH; Bethesda, MD, USA) [EY015240];
   Research to Prevent Blindness; FM Kirby Foundation; Paul and Evanina
   Bell Mackall Foundation Trust; NATIONAL EYE INSTITUTE [P30EY001583,
   R01EY015240] Funding Source: NIH RePORTER
FX Supported by the Pennsylvania Lions Eye Resarch and Sight Conservation
   Foundation, National Institutes of Health (NIH; Bethesda, MD, USA) Grant
   EY015240, Research to Prevent Blindness, the FM Kirby Foundation, the
   Paul and Evanina Bell Mackall Foundation Trust, and a gift in memory of
   Dr. Lee F. Mauger.
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NR 54
TC 29
Z9 29
U1 2
U2 19
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 SEP
PY 2014
VL 55
IS 9
BP 5979
EP 5988
DI 10.1167/iovs.14-15025
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AQ9DX
UT WOS:000343146900066
PM 25146987
OA Green Published
DA 2022-11-30
ER

PT J
AU Singh, RSJ
   Kim, JE
AF Singh, Ravi S. J.
   Kim, Judy E.
TI Ocular Hypertension Following Intravitreal Anti-vascular Endothelial
   Growth Factor Agents
SO DRUGS & AGING
LA English
DT Review
ID INTRAOCULAR-PRESSURE CHANGES; OPEN-ANGLE GLAUCOMA; MACULAR DEGENERATION;
   PEGAPTANIB SODIUM; DOSING REGIMEN; UNITED-STATES; RANIBIZUMAB;
   BEVACIZUMAB; INJECTION; PREVALENCE
AB Age-related macular degeneration (AMD) is the leading cause of severe vision loss in adults over the age of 65 years. The advent of anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections has revolutionized the management of exudative AMD. However, multiple case series of sustained elevated intraocular pressure (IOP) after intravitreal injections of anti-VEGF agents have been reported. Sustained elevated IOP has been reported with all anti-VEGF agents being used in ophthalmology and even in patients without any prior history of glaucoma. No clear correlations to injection frequency or patient characteristics have emerged from the multiple reports so far, but it appears that patients with preexisting glaucoma or ocular hypertension and those receiving a greater number of injections with shorter injection intervals may be at a higher risk for developing ocular hypertension related to anti-VEGF agents. Until future studies elucidate the pathophysiology of sustained IOP following anti-VEGF injections, it is prudent to recognize the possibility of elevations in IOP in association with anti-VEGF therapy. Treating physicians should look for subtle optic nerve head changes and IOP measurements suspicious for glaucoma and have a low threshold for treating elevated IOP if the patient is likely to require multiple intravitreal anti-VEGF injections. Ocular hypertension following anti-VEGF injections appears to be amenable to anti-glaucoma treatment and every effort should be made to preserve the peripheral vision in these patients where central vision is already threatened by exudative AMD.
C1 [Singh, Ravi S. J.; Kim, Judy E.] Med Coll Wisconsin, Inst Eye, Dept Ophthalmol, Milwaukee, WI 53226 USA.
C3 Medical College of Wisconsin
RP Kim, JE (通讯作者)，Med Coll Wisconsin, Inst Eye, Dept Ophthalmol, 925 N 87th St, Milwaukee, WI 53226 USA.
EM jekim@mcw.edu
FU Research to Prevent Blindness, Inc., New York, NY, USA
FX Funding for the preparation of this article was provided in part by an
   unrestricted grant from Research to Prevent Blindness, Inc., New York,
   NY, USA. The authors have no conflicts of interest that are directly
   relevant to the content of this article.
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NR 51
TC 22
Z9 23
U1 0
U2 5
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 2012
VL 29
IS 12
BP 949
EP 956
DI 10.1007/s40266-012-0031-2
PG 8
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 059CX
UT WOS:000312683100003
PM 23179897
DA 2022-11-30
ER

PT J
AU Zhou, P
   Fan, L
   Yu, KD
   Zhao, MW
   Li, XX
AF Zhou, Peng
   Fan, Lei
   Yu, Ke-Da
   Zhao, Ming-Wei
   Li, Xiao-Xin
TI Toll-like receptor 3 C1234T may protect against geographic atrophy
   through decreased dsRNA binding capacity
SO FASEB JOURNAL
LA English
DT Article
DE age-related macular degeneration; double-stranded RNA
ID MACULAR DEGENERATION; FUNCTIONAL ANALYSES; POLYMORPHISMS
AB The genetic association between a variant in the Toll-like receptor 3 (TLR3) gene (C1234T in mRNA, L412F in protein, Reference SNP Cluster Report rs3775291) and geographic atrophy (GA; also called advanced "dry" age-related macular degeneration) was controversial in previous studies. We performed a meta-analysis by pooling the current evidence in literature and found that the T allele of the TLR3 C1234T variant showed a summary odds ratio of 0.753 (95% confidence interval: 0.612-0.927; P=0.007). Further experiments were performed to analyze how this mutant influences the function of TLR3. We found that this SNP did not affect mRNA, protein, or surface expression of TLR3. However, the binding capacity of L412F mutation of TLR3 for double-stranded RNA in the TLR3 protein was only 51.12 +/- 3.96% (P<0.001) of the wild-type level. There was a consistently reduced TLR3-mediated NF-kappa B activation. Therefore, TLR3 C1234T (L412F in the protein) may protect against GA by reduced binding capacity of TLR3 to dsRNA. This study may provide a better understanding of the genetic architecture underlying disease susceptibility and may advance the potential for preclinical prediction in future genetic testing.-Zhou, P., Fan, L., Yu, K. -D., Zhao, M. -W., Li, X. -X. Toll-like receptor 3 C1234T may protect against geographic atrophy through decreased dsRNA binding capacity, FASEB J. 25, 3489-3495 (2011). www.fasebj.org
C1 [Zhou, Peng; Zhao, Ming-Wei; Li, Xiao-Xin] Peking Univ Peoples Hosp, Dept Ophthalmol, Beijing 100044, Peoples R China.
   [Zhou, Peng; Zhao, Ming-Wei; Li, Xiao-Xin] Minist Educ, Key Lab Vis Loss & Restorat, Beijing, Peoples R China.
   [Zhou, Peng] Fudan Univ, Eye & Ear Nose & Throat Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China.
   [Fan, Lei; Yu, Ke-Da] Fudan Univ, Dept Breast Surg, Ctr Canc, Inst Canc, Shanghai 200433, Peoples R China.
C3 Peking University; Fudan University; Fudan University
RP Li, XX (通讯作者)，Peking Univ Peoples Hosp, Dept Ophthalmol, 11 S Ave XiZhiMen, Beijing 100044, Peoples R China.
EM drxiaoxinli@gmail.com
RI Zhou, Peng/C-6054-2008
OI Zhou, Peng/0000-0002-1744-5167
FU National Basic Research Program of China (973 Program) [2011CB510200]
FX This research was supported by National Basic Research Program of China
   (973 Program) grant 2011CB510200.
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NR 20
TC 42
Z9 45
U1 0
U2 10
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 OCT
PY 2011
VL 25
IS 10
BP 3489
EP 3495
DI 10.1096/fj.11-189258
PG 7
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 826LU
UT WOS:000295356400019
PM 21712495
DA 2022-11-30
ER

PT J
AU Brown, NH
   Koreishi, AF
   McCall, M
   Izatt, JA
   Rickman, CB
   Toth, CA
AF Brown, Ninita H.
   Koreishi, Anjum F.
   McCall, Michelle
   Izatt, Joseph A.
   Rickman, Catherine Bowes
   Toth, Cynthia A.
TI Developing SDOCT to assess donor human eyes prior to tissue sectioning
   for research
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; SDOCT; Human donor eyes; Drusen
ID OPTICAL COHERENCE TOMOGRAPHY; PERIPHERAL RETINAL LESIONS; AGE-RELATED
   MACULOPATHY; IN-VIVO; HISTOLOGIC CORRELATION; MACULAR DEGENERATION;
   GRADING SYSTEM; RODENT RETINA; HIGH-SPEED; IMAGES
AB To compare spectral domain optical coherence tomography (SDOCT) cross-sectional images of human central retina obtained from donor eyes with and without age-related macular degeneration (AMD) to corresponding histopathology from light micrographs. To establish the utility of SDOCT for localizing pathology in the posterior eyecup, for identifying ocular disease in donor eyes, or for directing subsequent sectioning of retinal lesions for research.
   Seven consecutive human donor eyes were selected based on age. The eyes, with the anterior segment removed, were imaged by SDOCT with a focusing aspheric lens. Four eyes were from donors with a clinical history of AMD, and three were from age-matched donors with no history of AMD. Histopathological correlation of morphological changes detected in three eyes by SDOCT was obtained for comparison to step serial-sectioned light microscopy images of the formalin-fixed, paraffin-embedded retina. A simplified imaging setup was tested on an enucleated porcine eye for comparison.
   AMD pathology was detected and localized in four eyes by SDOCT. The SDOCT images correlated with the histopathology observed by light microscopy in each sectioned eye. Pathologies included a subfoveal neovascular lesion with subretinal fluid, peripapillary neovascularization, epiretinal membrane, foveal cyst, choroidal folds, and drusen. Similar imaging was possible with the simplified setup.
   SDOCT imaging identified retinal disease of the posterior eyecup in human donor eyes. Pathology detected with SDOCT was verified by light microscopy in three eyes, supporting the utility of SDOCT as a screening tool for research.
C1 [Brown, Ninita H.; Izatt, Joseph A.; Toth, Cynthia A.] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA.
   [Koreishi, Anjum F.; McCall, Michelle; Izatt, Joseph A.; Rickman, Catherine Bowes; Toth, Cynthia A.] Duke Univ, Ctr Eye, Dept Ophthalmol, Durham, NC 27710 USA.
   [Rickman, Catherine Bowes] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
C3 Duke University; Duke University; Duke University
RP Toth, CA (通讯作者)，Duke Univ, Ctr Eye, Dept Ophthalmol, Erwin Rd, Durham, NC 27710 USA.
EM cynthia.toth@duke.edu
RI Toth, Cynthia/L-5534-2019; toth, cynthia a/F-5614-2011; Izatt,
   Joseph/C-9067-2014
OI Toth, Cynthia/0000-0002-2324-0854; Izatt, Joseph/0000-0003-1993-2249;
   Bowes Rickman, Catherine/0000-0002-8555-9596
FU NIH [EB01630, 5R21EY017393-02]; NEI [P30EY005722]; Macular Vision
   Research Foundation; Ruth and Milton Steinbach Fund; Research to Prevent
   Blindness William; Mary Greve Special Scholars Award; NATIONAL EYE
   INSTITUTE [R21EY017393, P30EY005722] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
   [T32EB001630] Funding Source: NIH RePORTER
FX Authors acknowledge the contributions of Farshid Guilak for critically
   reviewing the study proposal; Elizabeth Williams, Ramiro Maldonado, and
   Katrina Winter for collecting data; Sina Farsiu and Bradley Bower for
   serving as scientific advisors.; We gratefully acknowledge the financial
   support of the NIH under grant EB01630 (Brown), 5R21EY017393-02 (McCall,
   Izatt, Toth), and NEI P30EY005722 in addition to the Macular Vision
   Research Foundation (Bowes-Rickman), the Ruth and Milton Steinbach Fund
   (Bowes-Rickman), and the Research to Prevent Blindness William and Mary
   Greve Special Scholars Award (Bowes-Rickman).
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NR 44
TC 16
Z9 16
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 AUG
PY 2009
VL 247
IS 8
BP 1069
EP 1080
DI 10.1007/s00417-009-1044-3
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 469KK
UT WOS:000267896700008
PM 19225801
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Owsley, C
   McGwin, G
   Lee, PP
   Wasserman, N
   Searcey, K
AF Owsley, Cytithia
   McGwin, Gerald, Jr.
   Lee, Paul P.
   Wasserman, Nicole
   Searcey, Karen
TI Characteristics of Low-Vision Rehabilitation Services in the United
   States
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; VISUAL IMPAIRMENT; US ADULTS; EYE;
   OPHTHALMOLOGISTS; POPULATION; PREVALENCE; BLINDNESS; ACUITY; TRIAL
AB Objectives: To describe characteristics of services, providers, and patients in low-vision rehabilitation entities serving adults in the United States.
   Methods: Entities (excluding Veterans Affairs clinics) were identified through professional associations, Web searches, and a telephone survey to retina practices. A census obtained information on entity types, provider types, rehabilitation services available, and clientele. surveys were administered by telephone, fax, e-mail, or mail, whichever was preferred by the respondent.
   Results: A total of 1228 low-vision rehabilitation service entities were identified, with 608 surveyed (49.5% response rate). Almost half (42.7%) were private optometry practices. State agencies had the highest number of clients per week (45.0 clients per week) whereas private optometry practices had the lowest (4.1 clients per week). Most (>= 88.0%) established rehabilitation goals, fit optical aids with basic training, and conducted eye examinations. Scanning, eccentric viewing, orientation and mobility, and advanced device training were less commonly offered (25%-50% of entities). Central vision impairment was the most common deficit (74.1% of clients), with age-related macular degeneration being the most common cause (67.1%). Among the clients, 85.9% had problems reading and 67.7% had problems driving; 44.9% had adjustment disorders. Almost 1 in 3 clients was aged 80 years or older.
   Conclusion: This census for the first time characterizes usual-care low-vision rehabilitation services in the United States for nonveteran adults.
C1 [Owsley, Cytithia; McGwin, Gerald, Jr.; Wasserman, Nicole; Searcey, Karen] Univ Alabama, Dept Ophthalmol, Sch Med, Birmingham, AL 35294 USA.
   [McGwin, Gerald, Jr.] Univ Alabama, Dept Surg, Sch Med, Birmingham, AL 35294 USA.
   [McGwin, Gerald, Jr.] Univ Alabama, Dept Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA.
   [Lee, Paul P.] Duke Univ, Ctr Eye, Durham, NC 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; Duke
   University
RP Owsley, C (通讯作者)，Univ Alabama, Dept Ophthalmol, Sch Med, 700 S 18th St,Ste 609, Birmingham, AL 35294 USA.
EM owsley@uab.edu
RI Owsley, Cynthia/B-7986-2014
OI Lee, Paul/0000-0002-3338-136X
FU National Eye institute [R21-EY16801, R21-EY14071]; EyeSight Foundation
   of Alabama; Research to Prevent Blindness, Inc; Alfreda J. Schueler
   Trust; NATIONAL EYE INSTITUTE [R21EY014071, R21EY016801] Funding Source:
   NIH RePORTER
FX This work was supported by grants R21-EY16801 and R21-EY14071 from the
   National Eye institute and by the EyeSight Foundation of Alabama,
   Research to Prevent Blindness, Inc, and the Alfreda J. Schueler Trust.
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NR 37
TC 98
Z9 101
U1 0
U2 12
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD MAY
PY 2009
VL 127
IS 5
BP 681
EP 689
DI 10.1001/archophthalmol.2009.55
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 442NK
UT WOS:000265847700014
PM 19433720
OA Bronze, Green Accepted
DA 2022-11-30
ER

PT J
AU Gatto, B
   Palumbo, M
   Sissi, C
AF Gatto, B.
   Palumbo, M.
   Sissi, C.
TI Nucleic Acid Aptamers Based on the G-Quadruplex Structure: Therapeutic
   and Diagnostic Potential
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE G-quadruplex; aptamer; SELEX; DNA; RNA; anticoagulant; anticancer;
   antiviral; antirheumatic; diagnosis
ID IN-VITRO SELECTION; THROMBIN BINDING APTAMER; RNASE-H DOMAIN;
   NF-KAPPA-B; DNA APTAMERS; ANTIPROLIFERATIVE ACTIVITY; FORMING
   OLIGONUCLEOTIDES; INDUCE APOPTOSIS; ENZYME SUBUNIT; PROTEIN
AB Aptamers are short DNA-or RNA-based oligonucleotides selected from large combinatorial pools of sequences for their capacity to efficiently recognize targets ranging from small molecules to proteins or nucleic acid structures. Like antibodies, they exhibit high specificity and affinity for target binding. As a result, they may display effective interference in biological processes, which renders them not only valuable diagnostic tools, but also promising therapeutic agents. In fact, one aptamer that inhibits human VEGF already received approval for the treatment of age-related macular degeneration, while several others are undergoing clinical trials. Aptamers display a large number of structural arrangements, which accounts for their binding efficiency and selectivity for unrelated targets. Among several architectures, the G-quadruplex (G-4) is adopted by several aptamers, the most popular of which shows inhibitory properties against thrombin, a pharmacologically relevant protein. G-4 structures consist of planar arrays of four guanines, each guanine pairing with two neighbours by Hoogsteen bonding. Recent work shows that G-4 arrangement is highly polymorphic and therefore represents a large family of stable structures with a common overall fold, but with well differentiated recognition elements that allow prominent diversity to be explored. Conformational plasticity consents fine tuning of target recognition as obtained by aptamer selection. Here, we will review the present knowledge on aptamers based on the G-4 structures and assess their diagnostic and therapeutic potential as biotech drugs for the detection and treatment of severe pathologies including vascular, cancer and viral diseases.
C1 [Gatto, B.; Palumbo, M.; Sissi, C.] Univ Padua, Dept Pharmaceut Sci, I-35131 Padua, Italy.
C3 University of Padua
RP Palumbo, M (通讯作者)，Univ Padua, Dept Pharmaceut Sci, Via Marzolo 5, I-35131 Padua, Italy.
EM manlio.palumbo@unipd.it
RI Gatto, Barbara/B-1542-2013
OI Gatto, Barbara/0000-0001-9465-6913; SISSI, CLAUDIA/0000-0002-9713-1415;
   Palumbo, Manlio/0000-0002-3163-1564
FU AIRC (Associazione Italiana per la Ricerca sul Cancro); Italian Board of
   Education (PRIN); University of Padova
FX The authors are indebted to AIRC (Associazione Italiana per la Ricerca
   sul Cancro), to the Italian Board of Education (PRIN) and to the
   University of Padova for financial support.
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   Zhu QQ, 2007, J COMPUT AID MOL DES, V21, P641, DOI 10.1007/s10822-007-9147-6
NR 101
TC 130
Z9 136
U1 3
U2 104
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 0929-8673
EI 1875-533X
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD APR
PY 2009
VL 16
IS 10
BP 1248
EP 1265
DI 10.2174/092986709787846640
PG 18
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
   Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 440HT
UT WOS:000265692100006
PM 19355883
DA 2022-11-30
ER

PT J
AU Li, SY
   Fu, ZJ
   Ma, H
   Jang, WC
   So, KF
   Wong, D
   Lo, ACY
AF Li, Suk-Yee
   Fu, Zhong-Jie
   Ma, Huan
   Jang, Wai-Chi
   So, Kwok-Fai
   Wong, David
   Lo, Amy C. Y.
TI Effect of Lutein on Retinal Neurons and Oxidative Stress in a Model of
   Acute Retinal Ischemia/Reperfusion
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; ISCHEMIA-REPERFUSION INJURY; RAT RETINA;
   GANGLION-CELLS; MACULAR PIGMENT; INNER RETINA; VITAMIN-E; EXPRESSION;
   ZEAXANTHIN; APOPTOSIS
AB PURPOSE. Retinal ischemia/reperfusion (I/R) occurs in many ocular diseases and leads to neuronal death. Lutein, a potent antioxidant, is used to prevent severe visual loss in patients with early age-related macular degeneration (AMD), but its effect on I/R insult is unclear. The objective of the present study is to investigate the neuroprotective effect of lutein on retinal neurons after acute I/R injury.
   METHODS. Unilateral retinal I/R was induced by the blockade of internal carotid artery using intraluminal method in mice. Ischemia was maintained for 2 hours followed by 22 hours of reperfusion, during which either lutein or vehicle was administered. The number of viable retinal ganglion cells (RGC) was quantified. Apoptosis was investigated using TUNEL assay. Oxidative stress was elucidated using markers such as nitrotyrosine (NT) and poly(ADP-ribose) (PAR).
   RESULTS. In vehicle-treated I/R retina, severe cell loss in ganglion cell layer, increased apoptosis as well as increased NT and nuclear PAR immunoreactivity were observed. In lutein-treated I/R retina, significantly less cell loss, decreased number of apoptotic cells, and decreased NT and nuclear PAR immunoreactivity were seen.
   CONCLUSIONS. The neuroprotective effect of lutein was associated with reduced oxidative stress. Lutein has been hitherto used principally for protection of outer retinal elements in AMD. Our study suggests that it may also be relevant for the protection of inner retina from acute ischemic damage. (Invest Ophthalmol Vis Sci. 2009;50:836-843) DOI:10.1167/iovs.08-2310
C1 [Li, Suk-Yee; Fu, Zhong-Jie; Ma, Huan; Jang, Wai-Chi; Wong, David; Lo, Amy C. Y.] Univ Hong Kong, Inst Eye, Li Ka Shing Fac Med, Pokfulam, Hong Kong, Peoples R China.
   [So, Kwok-Fai] Univ Hong Kong, Dept Anat, Li Ka Shing Fac Med, Pokfulam, Hong Kong, Peoples R China.
   [So, Kwok-Fai] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Pokfulam, Hong Kong, Peoples R China.
   [So, Kwok-Fai; Wong, David; Lo, Amy C. Y.] Univ Hong Kong, Res Ctr Heart Brain Hormone & Healthy Aging, Pokfulam, Hong Kong, Peoples R China.
   [Wong, David] Royal Liverpool Univ Hosp, St Pauls Eye Unit, Liverpool, Merseyside, England.
C3 University of Hong Kong; University of Hong Kong; University of Hong
   Kong; University of Hong Kong; Royal Liverpool & Broadgreen University
   Hospitals NHS Trust; Royal Liverpool University Hospital; University of
   Liverpool
RP Lo, ACY (通讯作者)，Univ Hong Kong, Inst Eye, Li Ka Shing Fac Med, Pokfulam, Hong Kong, Peoples R China.
EM amylo@hkucc.hku.hk
RI Lo, Amy C. Y./C-1195-2009; Wong, Sai Hung David/D-8482-2015
OI Lo, Amy C. Y./0000-0003-4239-6851; So, Kwok-Fai/0000-0003-4039-4246; FU,
   ZHONGJIE/0000-0002-8182-2983
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NR 57
TC 95
Z9 103
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 FEB
PY 2009
VL 50
IS 2
BP 836
EP 843
DI 10.1167/iovs.08-2310
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 397MD
UT WOS:000262665900046
PM 18936152
DA 2022-11-30
ER

PT J
AU Pallikaris, A
   Skondra, D
   Karavvela, M
   Tsilimbaris, M
AF Pallikaris, Aristophanis
   Skondra, Dimitra
   Karavvela, Marieta
   Tsilimbaris, Miltiadis
TI Confocal Scanning Laser Tomography Analysis of Choroidal
   Neovascularization and Correlation with Quantitative Fluorescein
   Angiography
SO CURRENT EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; confocal scanning laser
   ophthalmoscopy; fluorescein angiography; photodynamic therapy; retinal
   imaging
ID OPTICAL COHERENCE TOMOGRAPHY; RANDOMIZED CLINICAL-TRIAL; DIABETIC
   MACULAR EDEMA; REPORT NO. 1; PHOTODYNAMIC THERAPY; PATHOLOGICAL MYOPIA;
   VERTEPORFIN THERAPY; VISUAL FUNCTION; DEGENERATION; MEMBRANES
AB Purpose: To investigate the agreement between confocal scanning laser tomography and quantitative fluorescein angiography in the analysis of retinal-thickness changes in patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Materials and Methods: The edema index of a cSLT was measured in 18 eyes of 16 patients with CNV secondary to AMD that underwent photodynamic therapy (PDT) with Visudyne. Measurements were taken 1 hour before as well as 1 hour, 1 month, and 3 months after therapy. Moreover, a custom-written algorithm was used to analyze the integrated contrast amplitude (ICA) of fluorescein angiograms acquired before as well as 1 month and 3 months after PDT. Confocal scanning laser analysis of the edema index (EI) before and after PDT and correlation of the results with quantitative fluorescein angiography was performed. Results: A statistical significant increase of the EI was observed 1 hour after PDT. Nonetheless, no other statistical significant change over time was observed either on the EI or the ICA. Significant correlation was observed between the EI and the ICA as well as their changes over time, yet better results were observed when non-parametric correlation was calculated.Conclusions: The axial intensity profile of the cSLT and the edema index provide important information with respect to the neovascular membranes and correlate well with quantitative fluorescein angiography. The application of cSLT and the EI provide an important tool that could complement the investigation of new treatments of neovascular membranes.
C1 [Pallikaris, Aristophanis; Karavvela, Marieta; Tsilimbaris, Miltiadis] Univ Crete, Inst Vis & Opt, Iraklion 71003, Greece.
   [Skondra, Dimitra] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
C3 University of Crete; Harvard University; Massachusetts Eye & Ear
   Infirmary
RP Pallikaris, A (通讯作者)，Univ Crete, Inst Vis & Opt, Iraklion 71003, Greece.
EM apallik@med.uoc.gr
OI Tsilimbaris, Miltiadis/0000-0002-0130-1150
CR Arnold J, 2001, OPHTHALMOLOGY, V108, P841
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NR 32
TC 1
Z9 1
U1 0
U2 2
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 4
BP 319
EP 327
AR PII 910508903
DI 10.1080/02713680902796153
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 434RT
UT WOS:000265292500010
PM 19373581
DA 2022-11-30
ER

PT J
AU Ezzat, MK
   Hann, CR
   Vuk-Pavlovic, S
   Pulido, JS
AF Ezzat, M-K
   Hann, C. R.
   Vuk-Pavlovic, S.
   Pulido, J. S.
TI Immune cells in the human choroid
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID SENILE MACULAR DEGENERATION; AGE-RELATED MACULOPATHY; DENDRITIC CELLS;
   BRUCHS MEMBRANE; EYE; NEOVASCULARIZATION; MACROPHAGES; EXPRESSION;
   SYSTEM; PREVALENCE
AB Aim: To characterise the leucocytes in human macular choroid with and without drusen, and in eyes with advanced age-related macular degeneration (AMD) with fibrovascular scarring (FVS).
   Methods: Ten eyes from nine donors ( range 55-91 years of age) were obtained from an eye bank within 38 h post mortem. Fixed macular biopsies were sectioned, stained immunochemically and examined for the presence of leucocyte antigens CD45, CD4, CD8, CD14 and CD83.
   Results: Four eyes without drusen, four eyes with drusen and two eyes with FVS contained 23.9 ( SD 6.2)%, 27.5 (7.2)%, and 19.3 (11.3)% CD45-positive cells, respectively. The corresponding percentages for CD4-positive cells were 5.4 (4.3), 8.9 (3.0) and 7.5 (8.1); for CD8-positive cells, 3.8 (0.7), 6.8 (2.2) and 6.3 (2.1); and for CD14-positive cells, 3.7 ( 3.7), 3.6 (1.6) and 2.6 ( 3.6), respectively. The authors found CD83-positive cells solely in one of the two FVS eyes examined that had the more severe form of scarring.
   Conclusion: Human choroid contains similar amounts of CD4-positive cells and monocytes irrespective of the presence of drusen, but CD8-positive cells are more abundant in macular choroid with drusen. The presence of haematopoietic cells in the macular choroid provides further evidence for the possible participation of inflammatory cells in pathogenesis of AMD.
C1 [Ezzat, M-K; Hann, C. R.; Pulido, J. S.] Mayo Clin, Dept Ophthalmol, Ctr Canc, Rochester, MN 55905 USA.
   [Vuk-Pavlovic, S.] Mayo Clin, Ctr Canc, Stem Cell Lab, Rochester, MN 55905 USA.
C3 Mayo Clinic; Mayo Clinic
RP Pulido, JS (通讯作者)，Mayo Clin, Dept Ophthalmol, Ctr Canc, 200 1st St SW, Rochester, MN 55905 USA.
EM Pulido.jose@mayo.edu
CR Anderson DH, 2002, AM J OPHTHALMOL, V134, P411, DOI 10.1016/S0002-9394(02)01624-0
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NR 26
TC 45
Z9 45
U1 0
U2 2
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 JUL
PY 2008
VL 92
IS 7
BP 976
EP 980
DI 10.1136/bjo.2007.129742
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 318RL
UT WOS:000257109700024
PM 18577650
DA 2022-11-30
ER

PT J
AU Liu, J
   Yan, SX
   Lu, N
   Yang, DN
   Lv, HY
   Wang, SL
   Zhu, X
   Zhao, YQ
   Wang, Y
   Ma, ZH
   Yu, Y
AF Liu, Jian
   Yan, Shixin
   Lu, Nan
   Yang, Dongni
   Lv, Hongyu
   Wang, Shuanglian
   Zhu, Xin
   Zhao, Yuqian
   Wang, Yi
   Ma, Zhenhe
   Yu, Yao
TI Automated retinal boundary segmentation of optical coherence tomography
   images using an improved Canny operator
SO SCIENTIFIC REPORTS
LA English
DT Article
ID SD-OCT IMAGES; LAYER SEGMENTATION; MACULAR EDEMA; THICKNESS;
   CLASSIFICATION; FLUID; PERFORMANCE; DRUSEN; EYES
AB Retinal segmentation is a prerequisite for quantifying retinal structural features and diagnosing related ophthalmic diseases. Canny operator is recognized as the best boundary detection operator so far, and is often used to obtain the initial boundary of the retina in retinal segmentation. However, the traditional Canny operator is susceptible to vascular shadows, vitreous artifacts, or noise interference in retinal segmentation, causing serious misdetection or missed detection. This paper proposed an improved Canny operator for automatic segmentation of retinal boundaries. The improved algorithm solves the problems of the traditional Canny operator by adding a multi-point boundary search step on the basis of the original method, and adjusts the convolution kernel. The algorithm was used to segment the retinal images of healthy subjects and age-related macular degeneration (AMD) patients; eleven retinal boundaries were identified and compared with the results of manual segmentation by the ophthalmologists. The average difference between the automatic and manual methods is: 2-6 microns (1-2 pixels) for healthy subjects and 3-10 microns (1-3 pixels) for AMD patients. Qualitative method is also used to verify the accuracy and stability of the algorithm. The percentage of "perfect segmentation" and "good segmentation" is 98% in healthy subjects and 94% in AMD patients. This algorithm can be used alone or in combination with other methods as an initial boundary detection algorithm. It is easy to understand and improve, and may become a useful tool for analyzing and diagnosing eye diseases.
C1 [Liu, Jian; Yan, Shixin; Zhao, Yuqian; Wang, Yi; Ma, Zhenhe; Yu, Yao] Northeastern Univ Qinhuangdao, Sch Control Engn, Qinhuangdao 066004, Hebei, Peoples R China.
   [Liu, Jian; Wang, Yi; Ma, Zhenhe; Yu, Yao] Hebei Key Lab Micronano Precis Opt Sensing & Meas, Qinhuangdao 066004, Hebei, Peoples R China.
   [Lu, Nan; Yang, Dongni] First Hosp Qinhuangdao, Dept Ophthalmol, Qinhuangdao 066004, Hebei, Peoples R China.
   [Lv, Hongyu] Qinhuangdao Maternal & Child Hlth Hosp, Dept Ophthalmol, Qinhuangdao 066004, Hebei, Peoples R China.
   [Wang, Shuanglian] Tangshan Maternal & Children Hosp, Tang Shan 063000, Peoples R China.
   [Zhu, Xin] Univ Aizu, Biomed Informat Engn Lab, Aizu Wakamatsu, Fukushima 9650053, Japan.
C3 Northeastern University - China; University of Aizu
RP Yu, Y (通讯作者)，Northeastern Univ Qinhuangdao, Sch Control Engn, Qinhuangdao 066004, Hebei, Peoples R China.; Yu, Y (通讯作者)，Hebei Key Lab Micronano Precis Opt Sensing & Meas, Qinhuangdao 066004, Hebei, Peoples R China.
EM y.j.yu@outlook.com
FU National Natural Science Foundation of China [61771119, 61901100,
   62075037]; Natural Science Foundation of Hebei Province [H2019501010,
   F2019501132, E2020501029, F2020501040]
FX This work was supported in part by National Natural Science Foundation
   of China (61771119, 61901100 and 62075037), Natural Science Foundation
   of Hebei Province (H2019501010, F2019501132, E2020501029 and
   F2020501040).
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NR 47
TC 1
Z9 1
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U2 11
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 26
PY 2022
VL 12
IS 1
AR 1412
DI 10.1038/s41598-022-05550-y
PG 16
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA YQ3SO
UT WOS:000749232200028
PM 35082355
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Im, S
   Han, JW
   Park, EJ
   Bang, JH
   Shin, HJ
   Chang, HS
   Woo, KM
   Park, WJ
   Park, TK
AF Im, Sora
   Han, Jung Woo
   Park, Euy Jun
   Bang, Ji Hong
   Shin, Hee Jeong
   Chang, Hun Soo
   Woo, Kee Min
   Park, Woo Jin
   Park, Tae Kwann
TI Suppression of choroidal neovascularization and epithelial-mesenchymal
   transition in retinal pigmented epithelium by adeno-associated
   virus-mediated overexpression of CCN5 in mice
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; GENE-THERAPY; CELLS;
   TRANSDUCTION; EXPRESSION; MANAGEMENT; RESPONSES; PROTEINS; FIBROSIS
AB Choroidal neovascularization (CNV) is a defining characteristic feature of neovascular age-related macular degeneration (nAMD) that frequently results in irreversible vision loss. The current strategies for the treatment of nAMD are mainly based on neutralizing vascular endothelial growth factor (VEGF). However, anti-VEGF therapies are often associated with subretinal fibrosis that eventually leads to damages in macula. In this study, we tested whether an anti-fibrotic and anti-angiogenic protein CCN5 can potentially be an effective and safe therapeutic modality in a mouse model of CNV. Laser photocoagulation was utilized to induce CNV, which was followed by intravitreal injection of recombinant adeno-associated virus serotype 2 encoding CCN5 (rAAV2-CCN5). Our data demonstrated that rAAV2-CCN5, but not a control viral vector, rAAV2-VLP, prominently attenuated both CNV lesions and angiogenesis. Aflibercept, which was utilized as a positive control, exhibited similar effects on CNV lesions and angiogenesis in our experimental settings. Upon laser photocoagulation, retinal pigmented epithelium (RPE) cells underwent significant morphological changes including cellular enlargement and loss of hexagonality. rAAV2-CCN5 significantly normalized these morphological defects. Laser photocoagulation also led to fibrotic deformation in RPE cells through inducing epithelial-mesenchymal transition (EMT), which was completely blocked by rAAV2-CCN5. In a striking contrast, aflibercept as well as rAAV2-VLP failed to exhibit any effects on EMT. Collectively, this study suggest that CCN5 might provide a potential novel strategy for the treatment of nAMD with a capability to inhibit CNV and fibrosis simaultaneously.
C1 [Im, Sora; Park, Euy Jun; Park, Woo Jin] Gwangju Inst Sci & Technol, Coll Life Sci, Gwangju, South Korea.
   [Han, Jung Woo; Park, Tae Kwann] Soonchunhyang Univ, Coll Med, Dept Ophthalmol, Bucheon, South Korea.
   [Bang, Ji Hong; Shin, Hee Jeong; Park, Tae Kwann] Bucheon Hosp, Soonchunhyang Grad Sch, Dept Interdisciplinary Program Biomed Sci, Bucheon, South Korea.
   [Chang, Hun Soo] Soonchunhyang Univ, Coll Med, Dept Anat, Cheonan, South Korea.
   [Chang, Hun Soo] Soonchunhyang Univ, Coll Med, BK21 Four Project, Cheonan, South Korea.
   [Woo, Kee Min; Park, Woo Jin] Olives Biotherapeut Inc, Gwangju, South Korea.
   [Park, Tae Kwann] Soonchunhyang Univ Hosp Bucheon, Lab Translat Res Retinal & Macular Degenerat, Bucheon, South Korea.
C3 Gwangju Institute of Science & Technology (GIST); Soonchunhyang
   University; Soonchunhyang University; Soonchunhyang University;
   Soonchunhyang University; Soonchunhyang University
RP Park, WJ (通讯作者)，Gwangju Inst Sci & Technol, Coll Life Sci, Gwangju, South Korea.; Park, TK (通讯作者)，Soonchunhyang Univ, Coll Med, Dept Ophthalmol, Bucheon, South Korea.; Park, TK (通讯作者)，Bucheon Hosp, Soonchunhyang Grad Sch, Dept Interdisciplinary Program Biomed Sci, Bucheon, South Korea.; Park, WJ (通讯作者)，Olives Biotherapeut Inc, Gwangju, South Korea.; Park, TK (通讯作者)，Soonchunhyang Univ Hosp Bucheon, Lab Translat Res Retinal & Macular Degenerat, Bucheon, South Korea.
EM woojinpark@icloud.com; tkpark@schmc.ac.kr
OI Shin, Hee Jeong/0000-0002-0944-6637
FU Korea Ministry of SMEs and Startups [S2842182]; National Research
   Foundation of Korea - Korean government (MSIT) [2022R1A4A200076711,
   2022R1A2C1004256]
FX K.M.W was supported by grant from Business for Startup growth and
   technological development (TIPS Program, S2842182) funded by Korea
   Ministry of SMEs and Startups in 2020. W.J.P was supported by grant from
   the National Research Foundation of Korea (2022R1A4A200076711,
   2022R1A2C1004256) funded by the Korean government (MSIT). MSIT is the
   abbreviation of Ministry of Science and ICT. The funder had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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TC 0
Z9 0
U1 1
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
PY 2022
VL 17
IS 6
AR e0269937
DI 10.1371/journal.pone.0269937
PG 16
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 3Y2RM
UT WOS:000843575700154
PM 35696413
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Xu, BH
   Zhou, LB
   Chen, QS
   Zhang, JN
   Huang, LJ
   Wang, SS
   Ye, ZM
   Ren, XR
   Cai, Y
   Jensen, LD
   Chen, WR
   Li, XR
   Ju, R
AF Xu, Bohan
   Zhou, Linbin
   Chen, Qishan
   Zhang, Jianing
   Huang, Lijuan
   Wang, Shasha
   Ye, Zhimin
   Ren, Xiangrong
   Cai, Yu
   Jensen, Lasse Dahl
   Chen, Weirong
   Li, Xuri
   Ju, Rong
TI Role of VEGFR2 in Mediating Endoplasmic Reticulum Stress Under Glucose
   Deprivation and Determining Cell Death, Oxidative Stress, and
   Inflammatory Factor Expression
SO FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE eye diseases; visual development; translational vision science; advanced
   technology; VEGFR2; ER stress; glucose deprivation
ID RETINAL-PIGMENT EPITHELIUM; N-LINKED GLYCOSYLATION; MACULAR
   DEGENERATION; MECHANISMS; RECEPTOR; GROWTH
AB Retinal pigment epithelium (RPE), a postmitotic monolayer located between the neuroretina and choroid, supports the retina and is closely associated with vision loss diseases such as age-related macular degeneration (AMD) upon dysfunction. Although environmental stresses are known to play critical roles in AMD pathogenesis and the roles of other stresses have been well investigated, glucose deprivation, which can arise from choriocapillary flow voids, has yet to be fully explored. In this study, we examined the involvement of VEGFR2 in glucose deprivation-mediated cell death and the underlying mechanisms. We found that VEGFR2 levels are a determinant for RPE cell death, a critical factor for dry AMD, under glucose deprivation. RNA sequencing analysis showed that upon VEGFR2 knockdown under glucose starvation, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are reduced. Consistently, VEGFR2 overexpression increased ER stress under the same condition. Although VEGFR2 was less expressed compared to EGFR1 and c-Met in RPE cells, it could elicit a higher level of ER stress induced by glucose starvation. Finally, downregulated VEGFR2 attenuated the oxidative stress and inflammatory factor expression, two downstream targets of ER stress. Our study, for the first time, has demonstrated a novel role of VEGFR2 in RPE cells under glucose deprivation, thus providing valuable insights into the mechanisms of AMD pathogenesis and suggesting that VEGFR2 might be a potential therapeutic target for AMD prevention, which may impede its progression.
C1 [Xu, Bohan; Zhou, Linbin; Chen, Qishan; Zhang, Jianing; Huang, Lijuan; Wang, Shasha; Ye, Zhimin; Ren, Xiangrong; Chen, Weirong; Li, Xuri; Ju, Rong] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China.
   [Cai, Yu] Chengdu Aier Eye Hosp, Chengdu, Peoples R China.
   [Jensen, Lasse Dahl] Linkoping Univ, Dept Med & Hlth Sci, Div Cardiovasc Med, Linkoping, Sweden.
C3 Sun Yat Sen University; Linkoping University
RP Chen, WR; Li, XR; Ju, R (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China.
EM chenwrq@aliyun.com; lixr6@mail.sysu.edu.cn; jurong@mail.sysu.edu.cn
RI Chen, Wei/GZK-7348-2022
FU State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun
   Yat-sen University in Guangzhou; National Natural Science Foundation of
   China [81470644]; Key Program of the National Natural Science Foundation
   of China [81330021]; NSFC-VR Collaboration Program of the National
   Natural Science Foundation of China [81611130082]
FX This research was supported by a grant of the State Key Laboratory of
   Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University in
   Guangzhou, the National Natural Science Foundation of China (81470644)
   to RJ, a Key Program of the National Natural Science Foundation of China
   (81330021), and a NSFC-VR Collaboration Program of the National Natural
   Science Foundation of China (81611130082) to XL.
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NR 43
TC 1
Z9 1
U1 2
U2 6
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 JUN 18
PY 2021
VL 9
AR 631413
DI 10.3389/fcell.2021.631413
PG 14
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA TC8RY
UT WOS:000668907100001
PM 34222224
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Waldstein, SM
   Seebock, P
   Donner, R
   Sadeghipour, A
   Bogunovic, H
   Osborne, A
   Schmidt-Erfurth, U
AF Waldstein, Sebastian M.
   Seeboeck, Philipp
   Donner, Rene
   Sadeghipour, Amir
   Bogunovic, Hrvoje
   Osborne, Aaron
   Schmidt-Erfurth, Ursula
TI Unbiased identification of novel subclinical imaging biomarkers using
   unsupervised deep learning
SO SCIENTIFIC REPORTS
LA English
DT Article
AB Artificial intelligence has recently made a disruptive impact in medical imaging by successfully automatizing expert-level diagnostic tasks. However, replicating human-made decisions may inherently be biased by the fallible and dogmatic nature of human experts, in addition to requiring prohibitive amounts of training data. In this paper, we introduce an unsupervised deep learning architecture particularly designed for OCT representations for unbiased, purely data-driven biomarker discovery. We developed artificial intelligence technology that provides biomarker candidates without any restricting input or domain knowledge beyond raw images. Analyzing 54,900 retinal optical coherence tomography (OCT) volume scans of 1094 patients with age-related macular degeneration, we generated a vocabulary of 20 local and global markers capturing characteristic retinal patterns. The resulting markers were validated by linking them with clinical outcomes (visual acuity, lesion activity and retinal morphology) using correlation and machine learning regression. The newly identified features correlated well with specific biomarkers traditionally used in clinical practice (r up to 0.73), and outperformed them in correlating with visual acuity (R2=0.46 compared to R2=0.29 for conventional markers), despite representing an enormous compression of OCT imaging data (67 million voxels to 20 features). In addition, our method also discovered hitherto unknown, clinically relevant biomarker candidates. The presented deep learning approach identified known as well as novel medical imaging biomarkers without any prior domain knowledge. Similar approaches may be worthwhile across other medical imaging fields.
C1 [Waldstein, Sebastian M.; Seeboeck, Philipp; Donner, Rene; Sadeghipour, Amir; Bogunovic, Hrvoje; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol & Optometry, Vienna Reading Ctr, Christian Doppler Lab Ophthalm Image Anal, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
   [Osborne, Aaron] Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
C3 Medical University of Vienna; Roche Holding; Genentech
RP Schmidt-Erfurth, U (通讯作者)，Med Univ Vienna, Dept Ophthalmol & Optometry, Vienna Reading Ctr, Christian Doppler Lab Ophthalm Image Anal, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
RI ; Bogunovic, Hrvoje/J-3445-2014
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311; Bogunovic,
   Hrvoje/0000-0002-9168-0894; Waldstein, Sebastian/0000-0003-2899-6279;
   Sadeghipour, Amir/0000-0003-2379-7895
FU Austrian Federal Ministry for Digital and Economic Affairs; National
   Foundation for Research, Technology and Development
FX The financial support by the Austrian Federal Ministry for Digital and
   Economic Affairs and the National Foundation for Research, Technology
   and Development is gratefully acknowledged. SMW, HB and US-E are members
   of the medical imaging cluster (MIC) at the Medical University of
   Vienna.
CR Busbee BG, 2013, OPHTHALMOLOGY, V120, P1046, DOI 10.1016/j.ophtha.2012.10.014
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NR 24
TC 12
Z9 12
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 31
PY 2020
VL 10
IS 1
AR 12954
DI 10.1038/s41598-020-69814-1
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA MV5QX
UT WOS:000556413400002
PM 32737379
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Karimi, P
   Gheisari, A
   Gasparini, SJ
   Baharvand, H
   Shekari, F
   Satarian, L
   Ader, M
AF Karimi, Padideh
   Gheisari, Ali
   Gasparini, Sylvia J.
   Baharvand, Hossein
   Shekari, Faezeh
   Satarian, Leila
   Ader, Marius
TI Crocetin Prevents RPE Cells from Oxidative Stress through Protection of
   Cellular Metabolic Function and Activation of ERK1/2
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration (AMD); oxidative stress; retinal
   pigment epithelium (RPE) cells; crocetin; energy production; ERK1/2
ID PIGMENT EPITHELIAL-CELLS; MITOCHONDRIAL ATP SYNTHASE; MACULAR
   DEGENERATION; INDUCED DAMAGE; VITAMIN-E; SAFFRON; DEATH; PROTEIN;
   NEUROPROTECTION; SUPPLEMENTATION
AB Age-related macular degeneration (AMD) is a leading cause for visual impairment in aging populations with limited established therapeutic interventions available. Oxidative stress plays an essential role in the pathogenesis of AMD, damaging the retinal pigment epithelium (RPE), which is essential for the function and maintenance of the light-sensing photoreceptors. This study aimed to evaluate the effects of crocetin, one of the main components of Saffron, on an in vitro RPE model of tert-butyl hydroperoxide (TBHP) induced oxidative stress using ARPE19 cells. The effects of crocetin were assessed using lactate de-hydrogenase (LDH) and ATP assays, as well as immunocytochemistry for cell morphology, junctional integrity, and nuclear morphology. The mechanism of crocetin action was determined via assessment of energy production pathways, including mitochondrial respiration and glycolysis in real-time as well as investigation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and distribution. Our results show that crocetin pre-treatment protects ARPE19 cells from TBHP-induced LDH release, intracellular ATP depletion, nuclear condensation, and disturbance of junctional integrity and cytoskeleton. The protective effect of crocetin is mediated via the preservation of energy production pathways and activation of ERK1/2 in the first minutes of TBHP exposure to potentiate survival pathways. The combined data suggest that a natural antioxidant, such as crocetin, represents a promising candidate to prevent oxidative stress in RPE cells and might halt or delay disease progression in AMD.
C1 [Karimi, Padideh; Gasparini, Sylvia J.; Ader, Marius] Tech Univ Dresden, CRTD Ctr Regenerat Therapies Dresden, Ctr Mol & Cellular Bioengn, D-01307 Dresden, Germany.
   [Gheisari, Ali] Tech Univ Dresden, CMCB Ctr Mol & Cellular Bioengn, D-01307 Dresden, Germany.
   [Baharvand, Hossein; Shekari, Faezeh] ACECR, Dept Stem Cells & Dev Biol, Cell Sci Res Ctr, Royan Inst Stem Cell Biol & Technol, Tehran 1665659911, Iran.
   [Baharvand, Hossein; Shekari, Faezeh] Univ Sci & Culture, Dept Dev Biol, Tehran 1665659911, Iran.
   [Satarian, Leila] ACECR, Dept Brain & Cognit Sci, Cell Sci Res Ctr, Royan Inst Stem Cell Biol & Technol, Tehran 1665659911, Iran.
C3 Technische Universitat Dresden; Technische Universitat Dresden; Academic
   Center for Education, Culture & Research (ACECR); Academic Center for
   Education, Culture & Research (ACECR)
RP Ader, M (通讯作者)，Tech Univ Dresden, CRTD Ctr Regenerat Therapies Dresden, Ctr Mol & Cellular Bioengn, D-01307 Dresden, Germany.; Satarian, L (通讯作者)，ACECR, Dept Brain & Cognit Sci, Cell Sci Res Ctr, Royan Inst Stem Cell Biol & Technol, Tehran 1665659911, Iran.
EM padideh.karimi_sejzei@mailbox.tu-dresden.de; ali.gheisari@tu-dresden.de;
   sylvia.gasparini@tu-dresden.de; baharvand@royaninstitute.org;
   faezehshekari@gmail.com; leilasatarian@royaninstitute.org;
   marius.ader@tu-dresden.de
RI Shekari, Faezeh/AEL-2145-2022; Satarian, Leila/M-3835-2017; Ader,
   Marius/E-7535-2010
OI Shekari, Faezeh/0000-0001-6026-5412; Satarian,
   Leila/0000-0002-5068-5031; Ader, Marius/0000-0001-9467-7677; Gasparini,
   Sylvia/0000-0002-3612-6428
FU Deutsche Forschungsgemeinschaft (DFG) [FZT111, EXC68]; Bundesministerium
   ftir Bildung und Forschung (BMBF) [01EK1613A]
FX This research was funded by Deutsche Forschungsgemeinschaft (DFG), grant
   number FZT111 and EXC68 (M.A.); Bundesministerium ftir Bildung und
   Forschung (BMBF) Research Grant 01EK1613A (M.A.).
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NR 99
TC 11
Z9 11
U1 1
U2 8
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 APR
PY 2020
VL 21
IS 8
AR 2949
DI 10.3390/ijms21082949
PG 24
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA LR3AC
UT WOS:000535565300291
PM 32331354
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU White, CE
   Kwok, B
   Olabisi, RM
AF White, Corina E.
   Kwok, Bryan
   Olabisi, Ronke M.
TI Activin A improves retinal pigment epithelial cell survival on stiff but
   not soft substrates
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
LA English
DT Article
DE retinal pigment epithelial cells; RPE cells; Activin A; Bruch's
   membrane; modulus stiffness
ID BETA; MODULUS
AB In several retinal degenerative disease pathologies, such as dry age-related macular degeneration (AMD), the retinal pigment epithelium (RPE) cell monolayer becomes dysfunctional. Promising tissue engineering treatment approaches implant RPE cells on scaffolds into the subretinal space. However, these approaches are not without challenges. Two major challenges that must be addressed are RPE dedifferentiation and the inflammatory response to cell/scaffold implantation. Design and optimization of scaffold cues for the purpose of RPE transplantation remain relatively unexplored, specifically the mechanical properties of the scaffolds. Prior work from our group indicated that by varying substrate moduli significant differences could be induced in cell cytoskeleton structure, cellular activity, and expression of inflammatory markers. We hypothesized that Activin A would provide rescue effects for cells demonstrating dedifferentiated characteristics. Results demonstrated that for cells on low modulus scaffolds, the mechanical environment was the dominating factor and Activin A was unable to rescue these cells. However, Activin A did demonstrate rescue effects for cells on high modulus scaffolds. This finding indicates that when cultured on scaffolds with an appropriate modulus, exogenous factors, such as Activin A, can improve RPE cell expression, morphology, and activity, while an inappropriate scaffold modulus can have devastating effects on RPE survival regardless of chemical stimulation. These findings have broad implications for the design and optimization of scaffolds for long-term successful RPE transplantation. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2871-2880, 2018.
C1 [White, Corina E.; Kwok, Bryan; Olabisi, Ronke M.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA.
C3 Rutgers State University New Brunswick
RP Olabisi, RM (通讯作者)，Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA.
EM ronke.olabisi@rutgers.edu
RI Olabisi, Ronke M/A-6599-2011
OI Olabisi, Ronke M/0000-0003-3738-5250; Kwok, Bryan/0000-0002-5178-8219
FU National Institutes of Health National Institute of General Medical
   Sciences (NIH NIGMS) biotechnology training program [T32 GM008339]; US
   Department of Education Graduate Assistance in Areas of National Need
   (GAANN) [P200A150131]; New Jersey Space Grant Consortium (NJSGC);
   NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008339] Funding
   Source: NIH RePORTER
FX Contract grant sponsor: National Institutes of Health National Institute
   of General Medical Sciences (NIH NIGMS) biotechnology training program;
   contract grant number: T32 GM008339 (CE White); Contract grant sponsor:
   US Department of Education Graduate Assistance in Areas of National Need
   (GAANN); contract grant number: P200A150131 (CE White); Contract grant
   sponsor: New Jersey Space Grant Consortium (NJSGC) (B Kwok).
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NR 14
TC 5
Z9 5
U1 2
U2 10
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1549-3296
EI 1552-4965
J9 J BIOMED MATER RES A
JI J. Biomed. Mater. Res. Part A
PD NOV
PY 2018
VL 106
IS 11
BP 2871
EP 2880
DI 10.1002/jbm.a.36476
PG 10
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA HA5JD
UT WOS:000450305800008
PM 30367547
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Song, DL
   Mohammed, I
   Bhuyan, R
   Miwa, T
   Williams, AL
   Gullipalli, D
   Sato, S
   Song, Y
   Dunaief, JL
   Song, WC
AF Song, Delu
   Mohammed, Imran
   Bhuyan, Rupak
   Miwa, Takashi
   Williams, Allison Lesher
   Gullipalli, Damodar
   Sato, Sayaka
   Song, Ying
   Dunaief, Joshua L.
   Song, Wen-Chao
TI Retinal Basal Laminar Deposits in Complement fH/fP Mouse Model of Dense
   Deposit Disease
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE factor H; properdin; retinal degeneration; dense deposit disease
ID GLOMERULONEPHRITIS TYPE-II; HEMOLYTIC-UREMIC SYNDROME; AGE-RELATED
   MACULOPATHY; SUB-RPE DEPOSITS; MACULAR DEGENERATION; FACTOR-H; FUNDUS
   CHANGES; ALTERNATIVE PATHWAY; PROPERDIN DEFICIENCY; C3 GLOMERULOPATHY
AB PURPOSE. Dense deposit disease (DDD) is caused by dysregulation of the alternative pathway of the complement cascade and characterized by electron-dense deposits in the kidney glomerular basement membrane (GBM) and drusen in Bruch's membrane (BrM). Complement factor H (fH) and factor properdin (fP) regulate complement activation; fH inhibits alternative pathway (AP) activation, whereas fP promotes it. We report pathologic changes in eyes of an fH and fP double-mutant mouse, which we previously showed have dense deposits in the GBM and early mortality from nephropathy.
   METHODS. fH(m/m), fP(-/-), and fH(m/m) /fP(-/-) mice were generated on a C57BL/6-129J background. Fundus imaging at 8 weeks of age was followed by analysis via light and electron microscopy. Retinal function was assessed by electroretinography (ERG). Complement levels and localization were tested by immunohistochemistry and ELISA. Retinas of fH(m/m) /fP(-/-) mice treated with intraperitoneal injections of an anti-C5 antibody were compared to those of age-and genotype-matched mice injected with an isotype control antibody.
   RESULTS. fH(m/m) /fP(-/-) mice suffered early-onset retinal hypopigmented spots detected using in vivo retinal photography, and histologic examination showed basal laminar deposits (BLamD), degeneration of the photoreceptors, and RPE vacuolization. ERG showed diminished retinal function. The anti-C5 antibody was retina-protective.
   CONCLUSIONS. This unique mouse represents a new model of complement-mediated rapid-onset DDD, and could be useful in exploring the pathologic changes associated with BLamD in age-related macular degeneration.
C1 [Song, Delu; Bhuyan, Rupak; Song, Ying; Dunaief, Joshua L.] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Mohammed, Imran; Miwa, Takashi; Williams, Allison Lesher; Gullipalli, Damodar; Sato, Sayaka; Song, Wen-Chao] Univ Penn, Dept Syst Pharmacol & Translat Therapeut, Perelman Sch Med, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; University of
   Pennsylvania; Pennsylvania Medicine
RP Dunaief, JL (通讯作者)，305 Stellar Chance Labs, 422 Curie Blvd, Philadelphia, PA 19104 USA.; Song, WC (通讯作者)，Room 1254 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@mail.med.upenn.edu; songwe@mail.med.upenn.edu
RI Williams, Allison/AAG-1481-2019
OI Williams, Allison/0000-0002-2920-1733; Mohammed,
   Imran/0000-0002-8412-0768
FU National Institutes of Health (NIH; Bethesda, MD, USA) [RO1EY023709,
   RO1AI085596]; BrightFocus Foundation [M2011-051]; Research to Prevent
   Blindness; FM Kirby Foundation; Paul and Evanina Bell Mackall Foundation
   Trust; National Center for Advancing Translational Sciences of the NIH
   [KL2TR001879]; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
   [KL2TR001879] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [P30EY001583, R01EY023709] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI085596] Funding
   Source: NIH RePORTER
FX Supported by National Institutes of Health (NIH; Bethesda, MD, USA)
   Grants RO1EY023709 (WCS), RO1AI085596 (WCS), and RO1EY023709 (JLD); a
   grant from the BrightFocus Foundation M2011-051 (WCS); Research to
   Prevent Blindness (JLD); the FM Kirby Foundation (JLD); the Paul and
   Evanina Bell Mackall Foundation Trust (a gift in memory of Lee F.
   Mauger; JLD); and grant KL2TR001879 from the National Center for
   Advancing Translational Sciences of the NIH (DS).
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NR 63
TC 3
Z9 3
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 JUL
PY 2018
VL 59
IS 8
BP 3405
EP 3415
DI 10.1167/iovs.18-24133
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GM7KT
UT WOS:000438365900008
PM 30025090
OA Green Published, Green Accepted, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Miere, A
   Oubraham, H
   Amoroso, F
   Butori, P
   Astroz, P
   Semoun, O
   Bruyere, E
   Pedinielli, A
   Addou-Regnard, M
   Jung, C
   Cohen, SY
   Souied, EH
AF Miere, Alexandra
   Oubraham, Hassiba
   Amoroso, Francesca
   Butori, Pauline
   Astroz, Polina
   Semoun, Oudy
   Bruyere, Elsa
   Pedinielli, Alexandre
   Addou-Regnard, Manar
   Jung, Camille
   Cohen, Salomon Y.
   Souied, Eric H.
TI Optical Coherence Tomography Angiography to Distinguish Changes of
   Choroidal Neovascularization after Anti-VEGF Therapy: Monthly Loading
   Dose versus Pro Re Nata Regimen
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RANIBIZUMAB
AB Purpose. To compare the qualitative and quantitative choroidal neovascularization (CNV) changes after antivascular endothelial growth factor (anti-VEGF) therapy in treatment-naive and treated eyes with age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). Methods. Consecutive patients with neovascular AMD underwent multimodal imaging, including OCTA (AngioPlex, CIRRUS HD-OCT model 5000; Carl Zeiss Meditec, Inc., Dublin, OH) at baseline and at three monthly follow-up visits. Treatment-naive AMD patients undergoing anti-VEGF loading phase were included in group A, while treated patients were included in group B. Qualitative and quantitative OCTA analyses were performed on outer retina to choriocapillaris (ORCC) slab. CNV size was measured using a free image analysis software (ImageJ, open-source imaging processing software, 2.0.0). Results. Twenty-five eyes of 25 patients were enrolled in our study (mean age 78.32 +/- 6.8 years): 13 treatment-naive eyes in group A and 12 treated eyes in group B. While qualitative analysis revealed no significant differences from baseline to follow-up in the two groups, quantitative analysis showed in group A a significant decrease in lesion area (P = 0.023); in group B, no significant change in the lesion area was observed during anti-VEGF therapy (P = 0.93). Conclusion. Treatment-naive and treated eyes with CNV secondary to neovascular AMD respond differently to anti-VEGF therapy. This should be taken into account when using OCTA for CNV follow-up or planning therapeutic strategies.
C1 [Miere, Alexandra; Oubraham, Hassiba; Amoroso, Francesca; Butori, Pauline; Astroz, Polina; Semoun, Oudy; Bruyere, Elsa; Pedinielli, Alexandre; Addou-Regnard, Manar; Cohen, Salomon Y.; Souied, Eric H.] Univ Paris Est Creteil, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, Creteil, France.
   [Jung, Camille; Cohen, Salomon Y.; Souied, Eric H.] Ctr Hosp Intercommunal Creteil, GRC Macula, Clin Res Ctr, Creteil, France.
   [Jung, Camille; Cohen, Salomon Y.; Souied, Eric H.] Ctr Hosp Intercommunal Creteil, GRC Macula, Biol Resources Ctr, Creteil, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil;
   Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil;
   Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil
RP Souied, EH (通讯作者)，Univ Paris Est Creteil, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, Creteil, France.; Souied, EH (通讯作者)，Ctr Hosp Intercommunal Creteil, GRC Macula, Clin Res Ctr, Creteil, France.; Souied, EH (通讯作者)，Ctr Hosp Intercommunal Creteil, GRC Macula, Biol Resources Ctr, Creteil, France.
EM esouied@hotmail.com
RI Miere, Alexandra/AIC-4074-2022
OI Miere, Alexandra/0000-0003-4123-8210; JUNG, Camille/0000-0001-8486-8939;
   Semoun, Oudy/0000-0002-2103-7545
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NR 33
TC 19
Z9 21
U1 0
U2 4
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.
PY 2018
VL 2018
AR 3751702
DI 10.1155/2018/3751702
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FW6EZ
UT WOS:000425412300001
PM 29507810
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Nashine, S
   Chwa, M
   Kazemian, M
   Thaker, K
   Lu, S
   Nesburn, A
   Kuppermann, BD
   Kenney, MC
AF Nashine, Sonali
   Chwa, Marilyn
   Kazemian, Mina
   Thaker, Kunal
   Lu, Stephanie
   Nesburn, Anthony
   Kuppermann, Baruch D.
   Kenney, M. Cristina
TI Differential Expression of Complement Markers in Normal and AMD
   Transmitochondrial Cybrids
SO PLOS ONE
LA English
DT Article
ID MITOCHONDRIAL-NUCLEAR INTERACTIONS; H-RELATED PROTEIN; RETINAL-PIGMENT
   EPITHELIUM; C-REACTIVE PROTEIN; MACULAR DEGENERATION; DNA VARIANTS;
   CHOROIDAL NEOVASCULARIZATION; FUNCTIONAL-PROPERTIES; CELLS; RISK
AB Purpose
   Variations in mitochondrial DNA (mtDNA) and abnormalities in the complement pathways have been implicated in the pathogenesis of age-related macular degeneration (AMD). This study was designed to determine the effects of mtDNA from AMD subjects on the complement pathway.
   Methods
   Transmitochondrial cybrids were prepared by fusing platelets from AMD and age-matched Normal subjects with Rho0 (lacking mtDNA) human ARPE-19 cells. Quantitative PCR and Western blotting were performed to examine gene and protein expression profiles, respectively, of complement markers in these cybrids. Bioenergetic profiles of Normal and AMD cybrids were examined using the Seahorse XF24 flux analyzer.
   Results
   Significant decreases in the gene and protein expression of complement inhibitors, along with significantly higher levels of complement activators, were found in AMD cybrids compared to Older-Normal cybrids. Seahorse flux data demonstrated that the bioenergetic profiles for Older-Normal and Older-AMD cybrid samples were similar to each other but were lower compared to Young-Normal cybrid samples.
   Conclusion
   In summary, since all cybrids had identical nuclei and differed only in mtDNA content, the observed changes in components of complement pathways can be attributed to mtDNA variations in the AMD subjects, suggesting that mitochondrial genome and retrograde signaling play critical roles in this disease. Furthermore, the similar bioenergetic profiles of AMD and Older-Normal cybrids indicate that the signaling between mitochondria and nuclei are probably not via a respiratory pathway.
C1 [Nashine, Sonali; Chwa, Marilyn; Thaker, Kunal; Lu, Stephanie; Nesburn, Anthony; Kuppermann, Baruch D.; Kenney, M. Cristina] Univ Calif Irvine, Gavin Herbert Eye Inst, Irvine, CA USA.
   [Kazemian, Mina] Touro Univ Nevada, Coll Osteopath Med, Henderson, NV USA.
   [Lu, Stephanie] Long Beach Hosp, VA Med Ctr, Long Beach, CA USA.
   [Nesburn, Anthony] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   [Kenney, M. Cristina] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA.
C3 University of California System; University of California Irvine; Cedars
   Sinai Medical Center; University of California System; University of
   California Irvine
RP Kenney, MC (通讯作者)，Univ Calif Irvine, Gavin Herbert Eye Inst, Irvine, CA USA.; Kenney, MC (通讯作者)，Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA.
EM mkenney@uci.edu
RI NASHINE, SONALI/AAG-1474-2020
FU Arnold and Mabel Beckman Foundation; Discovery Eye Foundation; Guenther
   Foundation; Beckman Initiative for Macular Research; Polly and Michael
   Smith Foundation; Max Factor Family Foundation; Iris and B. Gerald
   Cantor Foundation; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
   [UL1TR001414] Funding Source: NIH RePORTER
FX This work was supported by the Arnold and Mabel Beckman Foundation,
   Discovery Eye Foundation, Guenther Foundation, Beckman Initiative for
   Macular Research, Polly and Michael Smith Foundation, Max Factor Family
   Foundation, Iris and B. Gerald Cantor Foundation and SRN is a Arnold and
   Mabel Beckman Fellow. 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 75
TC 22
Z9 22
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 AUG 3
PY 2016
VL 11
IS 8
AR e0159828
DI 10.1371/journal.pone.0159828
PG 20
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DT3GA
UT WOS:000381367800041
PM 27486856
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Maslov, MY
   Chernysheva, GA
   Smol'jakova, VI
   Aliev, OI
   Kolosova, NG
   Plotnikov, MB
AF Maslov, Mikhail Y.
   Chernysheva, Galina A.
   Smol'jakova, Vera I.
   Aliev, Oleg I.
   Kolosova, Natalia G.
   Plotnikov, Mark B.
TI Hemorheological parameters and their correlations in OXYS rats: A new
   model of hyperviscosity syndrome
SO CLINICAL HEMORHEOLOGY AND MICROCIRCULATION
LA English
DT Article
DE OXYS rats; hyperviscosity syndrome; whole blood viscosity; plasma
   viscosity; RBC aggregation; RBC deformability
ID MACULAR DEGENERATION; BLOOD-VISCOSITY; PATHOGENETIC FACTORS; AMD
AB Rheohaemapheresis aims to normalize major rheological parameters and is used to treat patients with dry age-related macular degeneration (AMD). While effective, this approach is invasive and requires specially trained personnel. Therefore, the search for novel effective compounds with hemorheological properties that can be taken orally to treat AMD is justified. The use of a robust rodent model of AMD with high blood viscosity is crucial to test the efficacy of potential hemorheological drugs to treat this disease. The objective of this study was to investigate whether OXYS rats, generally used as an animal model of AMD, have hyperviscosity syndrome. The results of this study show that blood viscosity in OXYS rats at low (3-10 s(-1)) and high (45-300 s(-1)) shear rates were 14-20% and 7-10% higher than in Wistar rats, while hematocrit and plasma viscosity were not different. Red blood cells (RBCs) in OXYS rats were more prone to aggregation as shown by 39% shorter half-time than in Wistar rats. RBCs were also more rigid in OXYS than in Wistar rats as shown by 21-33% lower index of elongation at the shear stress of 1-7 Pa. These data indicate that OXYS rats have hyperviscosity syndrome as the result of abnormal RBC deformability and aggregation. We propose to use OXYS rats as an animal model for preclinical studies to test compounds with hemorheological properties aimed to treat AMD.
C1 [Maslov, Mikhail Y.] Tufts Univ, Sch Med, Steward St Elizabeths Med Ctr, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02111 USA.
   [Chernysheva, Galina A.; Smol'jakova, Vera I.; Aliev, Oleg I.; Plotnikov, Mark B.] Russian Acad Med Sci, ED Goldberg Inst Pharmacol, Tomsk 634028, Russia.
   [Kolosova, Natalia G.] Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Novosibirsk 630090, Russia.
   [Aliev, Oleg I.; Plotnikov, Mark B.] Tomsk State Univ, Tomsk 634050, Russia.
C3 St. Elizabeth's Medical Center; Tufts University; Russian Academy of
   Medical Sciences; Russian Academy of Sciences; Tomsk National Research
   Medical Center; E. D. Goldberg Research Institute of Pharmacology &
   Regenerative Medicine; Russian Academy of Sciences; Institute of
   Cytology & Genetics ICG SB RAS; Tomsk State University
RP Plotnikov, MB (通讯作者)，Russian Acad Med Sci, ED Goldberg Inst Pharmacol, Siberian Branch, Lenin St 3, Tomsk 634028, Russia.
EM mbp2001@mail.ru
RI Kolosova, Nataliya G/AAR-7409-2020; Kolosova, Nataliya G/P-3178-2015;
   Vera, Smolyakova Vera Smolyakova/I-9414-2017; Chernysheva,
   Galina/Q-7270-2016; Plotnikov, Mark/P-8957-2016; Aliev, Oleg/I-8689-2017
OI Kolosova, Nataliya G/0000-0003-2398-8544; Kolosova, Nataliya
   G/0000-0003-2398-8544; Vera, Smolyakova Vera
   Smolyakova/0000-0001-9501-4664; Chernysheva, Galina/0000-0002-6438-5734;
   Plotnikov, Mark/0000-0002-0548-6586; Aliev, Oleg/0000-0001-9788-1235
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NR 41
TC 2
Z9 2
U1 0
U2 0
PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 1386-0291
EI 1875-8622
J9 CLIN HEMORHEOL MICRO
JI Clin. Hemorheol. Microcirc.
PY 2015
VL 60
IS 4
BP 405
EP 411
DI 10.3233/CH-141860
PG 7
WC Hematology; Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Hematology; Cardiovascular System & Cardiology
GA CT6ZU
UT WOS:000362963500006
PM 25062716
DA 2022-11-30
ER

PT J
AU Wang, QL
   Lin, XY
   Xiang, W
   Xiao, W
   He, MG
AF Wang, Qilin
   Lin, Xingyan
   Xiang, Wu
   Xiao, Wei
   He, Mingguang
TI Assessment of laser induction of Bruch's membrane disruption in monkey
   by spectral-domain optical coherence tomography
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; TIME-DOMAIN; MODEL
AB Purpose Laser-induced choroidal neovascularisation is a widely used model for age-related macular degeneration. The success rates of induction have been relatively low in large animals such as monkeys. Our study aimed to investigate the laser-induced damages to the Bruch's membrane of monkeys using the spectral-domain optical coherence tomography (OCT).
   Methods Laser photocoagulation was performed in the posterior and peripheral fundus of a rhesus monkey using a 532 nm laser. The lesions were examined by fundus photography and spectral-domain OCT immediately after the procedure. Fluorescein angiography was performed after 3 and 4 weeks in the animal to assess the development of choroidal neovascularisation.
   Results A total of 44 lesions were produced in both eyes of the animal. Subretinal bubbles with or without haemorrhage were observed at 41 spots during the procedure. Spectral-domain OCT showed that laser damages varied considerably among lesions and the disruption of the Bruch's membrane could be visualised at 23 spots on the OCT images. Leakage of fluorescein was only observed after 3 and 4 weeks within the macular area at lesions where Bruch's membrane disruptions had been detected by OCT.
   Conclusions The presence of subretinal bubbles with haemorrhage is not an accurate indicator for successful disruption of the Bruch's membrane. Instead, spectral-domain OCT provides a better alternative to assess the retinal damages to the Bruch's membrane during laser induction of choroidal neovascularisation in monkeys.
C1 [Wang, Qilin; Lin, Xingyan; Xiang, Wu; Xiao, Wei; He, Mingguang] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
C3 Sun Yat Sen University
RP He, MG (通讯作者)，Zhongshan Ophthalm Ctr, Guangzhou 510060, Guangdong, Peoples R China.
EM mingguang_he@yahoo.com
RI He, Mingguang/AAY-5239-2020
OI He, Mingguang/0000-0002-6912-2810; Wang, Qilin/0000-0001-6967-6197
FU Fundamental Research Funds of State Key Lab, National Natural Science
   Foundation of China [81125007]
FX Fundamental Research Funds of State Key Lab, National Natural Science
   Foundation of China 81125007.
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NR 15
TC 3
Z9 3
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 JAN
PY 2015
VL 99
IS 1
BP 119
EP 124
DI 10.1136/bjophthalmol-2014-305813
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AW6CW
UT WOS:000346358000024
PM 25336578
DA 2022-11-30
ER

PT J
AU Jo, H
   Patterson, V
   Stoessel, S
   Kuan, CY
   Hoh, J
AF Jo, Hakryul
   Patterson, Victoria
   Stoessel, Sean
   Kuan, Chia-Yi
   Hoh, Josephine
TI Protoporphyrins Enhance Oligomerization and Enzymatic Activity of HtrA1
   Serine Protease
SO PLOS ONE
LA English
DT Article
ID SMALL-VESSEL DISEASE; MACULAR DEGENERATION; FAMILY PROTEINS; QUALITY
   CONTROL; SERUM-ALBUMIN; CANCER; OXYGEN; GENE; THERAPY; TARGETS
AB High temperature requirement protein A1 (HtrA1), a secreted serine protease of the HtrA family, is associated with a multitude of human diseases. However, the exact functions of HtrA1 in these diseases remain poorly understood. We seek to unravel the mechanisms of HtrA1 by elucidating its interactions with chemical or biological modulators. To this end, we screened a small molecule library of 500 bioactive compounds to identify those that alter the formation of extracellular HtrA1 complexes in the cell culture medium. An initial characterization of two novel hits from this screen showed that protoporphyrin IX (PPP-IX), a precursor in the heme biosynthetic pathway, and its metalloporphyrin (MPP) derivatives fostered the oligomerization of HtrA1 by binding to the protease domain. As a result of the interaction with MPPs, the proteolytic activity of HtrA1 against Fibulin-5, a specific HtrA1 substrate in age-related macular degeneration (AMD), was increased. This physical interaction could be abolished by the missense mutations of HtrA1 found in patients with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Furthermore, knockdown of HtrA1 attenuated apoptosis induced by PPP-IX. These results suggest that PPP-IX, or its derivatives, and HtrA1 may function as co-factors whereby porphyrins enhance oligomerization and the protease activity of HtrA1, while active HtrA1 elevates the pro-apoptotic actions of porphyrin derivatives. Further analysis of this interplay may shed insights into the pathogenesis of diseases such as AMD, CARASIL and protoporphyria, as well as effective therapeutic development.
C1 [Jo, Hakryul; Patterson, Victoria; Stoessel, Sean; Hoh, Josephine] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA.
   [Jo, Hakryul; Patterson, Victoria; Stoessel, Sean; Hoh, Josephine] Yale Univ, Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT 06510 USA.
   [Kuan, Chia-Yi] Emory Univ, Sch Med & Childrens Healthcare Atlanta, Dept Pediat, Atlanta, GA USA.
C3 Yale University; Yale University; Children's Healthcare of Atlanta
   (CHOA); Emory University
RP Hoh, J (通讯作者)，Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA.
EM Josephine.hoh@yale.edu
FU Rosebay Medical Foundation; Yale Medical School Dean's Research Fund
FX This work was funded by Rosebay Medical Foundation and Yale Medical
   School Dean's Research Fund. No URL is available. 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 42
TC 8
Z9 8
U1 0
U2 10
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 15
PY 2014
VL 9
IS 12
AR e115362
DI 10.1371/journal.pone.0115362
PG 17
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AW9WY
UT WOS:000346607100070
PM 25506911
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Xu, X
   Weng, YH
   Xu, L
   Chen, H
AF Xu, Xu
   Weng, Yuhua
   Xu, Lu
   Chen, Hao
TI Sustained release of avastin (R) from polysaccharides cross-linked
   hydrogels for ocular drug delivery
SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
LA English
DT Article
DE Avastin; Cross-linked hydrogel; Ocular drug delivery
ID CHOROIDAL NEOVASCULARIZATION; CHITOSAN; BEVACIZUMAB; RANIBIZUMAB;
   DEGRADATION; ALGINATE; DISEASE
AB Avastin (R) was the first choice drug for the treatment of age related macular degeneration (AMD) and proliferative diabetic retinopathy in clinic. Due to its short half-time in intraocular, it was required repeat administration. In this paper, an in situ injectable polysaccharides cross-linked hydrogel was developed for potential ocular drug delivery of avastin. The polysaccharide cross-linked hydrogel was first synthesized by simple mixing of glycol chitosan and oxidized alginate aqueous solution, and then characterized by scanning electron microscopy (SEM) and rheometer. In vitro degradation test indicated that the degradation rate of hydrogels could be controlled by the varying the content of oxidized alginate in hydrogels. In vitro release study showed that the encapsulated avastin had an initial burst release at early stage (within 4 h) followed by a sustained release manner in period of 3 days. With the increase of oxidized alginate concentration in the hydrogel, the release rate of avastin from hydrogels declined accordingly. Meanwhile, the structure stability of avastin released from hydrogels at specific time intervals did not show apparent changes as compared with native avastin based on the analysis of SDS-polyacrylamide gel electrophoresis (SDS-PAEG). As a result, the developed in situ injectable polysaccharides cross-linked hydrogel with controllable degradation rate and drug release might be a versatile carrier for avastin to apply in ocular drug delivery. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Chen, Hao] Wenzhou Med Coll, Inst Biomed Engn, Sch Ophthalmol & Optometry, Wenzhou 325027, Peoples R China.
   Wenzhou Med Coll, Hosp Eye, Wenzhou 325027, Peoples R China.
C3 Wenzhou Medical University; Wenzhou Medical University
RP Chen, H (通讯作者)，Wenzhou Med Coll, Inst Biomed Engn, Sch Ophthalmol & Optometry, 270 Xueyuan Rd, Wenzhou 325027, Peoples R China.
EM dragonhaochen@163.com
FU Key Program for International S&T Cooperation Projects of China
   [2012DFB30020]; Science and Technology Bureau of Wenzhou City
   [Y20090245]
FX This work was supported by Key Program for International S&T Cooperation
   Projects of China (2012DFB30020) and Science and Technology Bureau of
   Wenzhou City (Y20090245).
CR Alonso MJ, 2003, J PHARM PHARMACOL, V55, P1451, DOI 10.1211/0022357022476
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NR 23
TC 87
Z9 91
U1 4
U2 100
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0141-8130
J9 INT J BIOL MACROMOL
JI Int. J. Biol. Macromol.
PD SEP
PY 2013
VL 60
BP 272
EP 276
DI 10.1016/j.ijbiomac.2013.05.034
PG 5
WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry; Polymer Science
GA 223WJ
UT WOS:000324842900038
PM 23748006
DA 2022-11-30
ER

PT J
AU Bressler, NM
   Boyer, DS
   Williams, DF
   Butler, S
   Francom, SF
   Brown, B
   Di Nucci, F
   Cramm, T
   Tuomi, LL
   Ianchulev, T
   Rubio, RG
AF Bressler, Neil M.
   Boyer, David S.
   Williams, David F.
   Butler, Steven
   Francom, Steven F.
   Brown, Benton
   Di Nucci, Flavia
   Cramm, Timothy
   Tuomi, Lisa L.
   Ianchulev, Tsontcho
   Rubio, Roman G.
TI CEREBROVASCULAR ACCIDENTS IN PATIENTS TREATED FOR CHOROIDAL
   NEOVASCULARIZATION WITH RANIBIZUMAB IN RANDOMIZED CONTROLLED TRIALS
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID VERTEPORFIN PHOTODYNAMIC THERAPY; ARTERIAL THROMBOEMBOLIC EVENTS;
   VISION-RELATED FUNCTION; MACULAR DEGENERATION
AB Purpose: To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration.
   Methods: Events in five trials (FOCUS, MARINA, ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring process. Exact methods, stratified by study, were used to test for treatment differences based on odds ratios. A stepwise logistic regression model was fit to classify subjects' risk for CVA based on medical history. Treatment differences in CVA rates at 1 year or 2 years were evaluated within risk groups using stratified exact methods.
   Results: Pooled 2-year CVA rates were <3%; odds ratios (95% confidence intervals) for CVA risk were 1.2 (0.4-4.4) for ranibizumab 0.3-mg versus control, 2.2 (0.8-7.1) for 0.5 mg versus control, and 1.5 (0.8-3.0) for 0.5-mg versus 0.3-mg ranibizumab. No substantial increased risk of CVA for 0.5 mg versus 0.3 mg was identified in pooled analyses or any of the individual trials. In pooled analyses, the difference between 0.5-mg ranibizumab and control was larger (7.7 [1.2-177]) among high-risk CVA patients.
   Conclusion: This analysis provided some evidence, although not definitive, of a potential increased risk of CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab. Continued monitoring for CVA within clinical trials seems warrented. RETINA 32:1821-1828, 2012
C1 [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Retina Div, Baltimore, MD 21287 USA.
   [Boyer, David S.] Retina Vitreous Associates Med Grp, Los Angeles, CA USA.
   [Williams, David F.] VitreoRetinal Surg PA, Minneapolis, MN USA.
   [Butler, Steven; Francom, Steven F.; Brown, Benton; Di Nucci, Flavia; Cramm, Timothy; Tuomi, Lisa L.; Ianchulev, Tsontcho; Rubio, Roman G.] Genentech Inc, San Francisco, CA 94080 USA.
C3 Johns Hopkins University; Retina Vitreous Associates Medical Group;
   Roche Holding; Genentech
RP Bressler, NM (通讯作者)，Johns Hopkins Univ, Sch Med & Hosp, Wilmer Eye Inst, Retina Div,Dept Ophthalmol, Maumenee 752,600 North,Wolfe St, Baltimore, MD 21287 USA.
EM nmboffice@jhmi.edu
FU Genentech, Inc., South San Francisco, CA; Allergan; Bausch Lomb; Carl
   Zeiss Meditec; Genentech; Notal Vision, Inc.; Novartis; Othera; QLT;
   Regeneron; Steba Pharmaceuticals
FX Supported financially by Genentech, Inc., South San Francisco, CA. Dr.
   N. M. Bressler's employer, Department of Ophthalmology, the Johns
   Hopkins University (JHU) but Dr. N. M. Bressler does not receive funding
   from Allergan, Bausch & Lomb, Carl Zeiss Meditec, Genentech, Notal
   Vision, Inc., Novartis, Othera, QLT, Regeneron, and Steba
   Pharmaceuticals for sponsored projects in which he is an investigator.
   He 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. Dr. D. S. Boyer has been a consultant to Alcon,
   Allergan, Genentech, Novartis, QLT, Regeneron, and Pfizer, and he has
   been a speaker for Alcon, Genentech, Novartis, and Pfizer. Dr. D. F.
   Williams has provided consulting services to Genentech. Drs. S. Butler,
   S. F. Francom, B. Brown, F. Di Nucci, T. Cramm, L. L. Tuomi, T.
   Ianchulev, and R. G. Rubio are employees of Genentech. The studies
   analyzed for this report were cosponsored by Genentech, Inc, South San
   Francisco, CA, and Novartis Pharma, A.G., Basel, Switzerland.
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NR 18
TC 62
Z9 62
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 OCT
PY 2012
VL 32
IS 9
BP 1821
EP 1828
DI 10.1097/IAE.0b013e31825db6ba
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 012EH
UT WOS:000309217800017
PM 23011184
DA 2022-11-30
ER

PT J
AU Babizhayev, MA
   Yegorov, YE
AF Babizhayev, Mark A.
   Yegorov, Yegor E.
TI Therapeutic Uses of Drug-Carrier Systems for Imidazole-Containing
   Dipeptide Compounds That Act as Pharmacological Chaperones and Have
   Significant Impact on the Treatment of Chronic Diseases Associated With
   Increased Oxidative Stress and the Formation of Advanced Glycation End
   Products
SO CRITICAL REVIEWS IN THERAPEUTIC DRUG CARRIER SYSTEMS
LA English
DT Review
DE natural imidazole-containing peptidomimetics; carcinine;
   N-acetylcarnosine; L-carnosine; leucyl-histidylhydrazide; chemical and
   pharmacological chaperones; skin care; photoaging; cosmetic science;
   alpha A-crystallin; ophthalmic treatment; age-related cataract;
   age-related macular degeneration; ocular complications of diabetes
ID CARCININE BETA-ALANYLHISTAMINE; HISTIDINE-CONTAINING DIPEPTIDE;
   CARNOSINE PROTECTS PROTEINS; FREE-RADICAL OXIDATION; HEAT-SHOCK
   PROTEINS; ALPHA-CRYSTALLIN; N-ACETYLCARNOSINE; CHEMICAL CHAPERONES;
   CU,ZN-SUPEROXIDE DISMUTASE; MOLECULAR CHAPERONES
AB The purpose of this study was to determine how the naturally occurring molecules N-acetylcarnosine, L-carnosine, and carcinine, which are chemical or pharmacological chaperones, affect the cells and biomolecules of patients with skin diseases, cosmetic skin lesions, or underlying clinically significant visual impairment such as age-related cataracts, age-related retinal degeneration, and ocular complications of diabetes. We evaluated and characterized the effects of cited pharmacological chaperones on enzyme activity, protein structure in tissues, and other biomarkers of diseases in skin cells and tissues or in ocular tissues (human cataractous and normal lenses) derived from ophthalmic patients or age-matched donors. The samples were used to test imidazole-containing peptidomimetic chemical/pharmacological chaperones in relation to oxidative stress induced by reaction with lipid peroxides or advanced non-enzymatic glycation processes. Chaperone function is characterized by interaction with other proteins, mediating their folding, transport, and interaction with other molecules, lipid peroxidation products, and membranes. Although these therapies remain on hold pending further investigation, we present growing evidence demonstrating the ability of N-acetylcarnosine (lubricant eye drops) or carcinine pharmacological chaperone therapy to act as novel treatments for age-related cataracts, age-related macular degeneration, and ocular complications of diabetes. Finally, we examine strategies for identifying potential chaperone compounds and for experimentally demonstrating chaperone and transglycating (de-glycation) types of activity in in vitro and in vivo models of human age-related eye diseases, such as cataracts, and advanced glycation tissue protein-engineered systems.
C1 [Babizhayev, Mark A.] Innovat Vis Prod Inc, New Castle, DE USA.
   [Babizhayev, Mark A.] Moscow Helmholtz Res Inst Eye Dis, Moscow, Russia.
   [Yegorov, Yegor E.] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow, Russia.
C3 Helmholtz National Medical Research Center of Eye Diseases; Russian
   Academy of Sciences; Engelhardt Institute of Molecular Biology, RAS
RP Babizhayev, MA (通讯作者)，Innovat Vis Prod Inc, Moscow Div, Ivanovskaya 20,Suite 74, Moscow 127434, Russia.
EM markbabizhayev@yahoo.com
FU Innovative Vision Products, Inc. (IVP, Delaware, USA); Russian
   Foundation for Basic Research [09-04-01071a]; Federal Agency for
   Education [P1293]
FX This work was planned, organized, and supported by Innovative Vision
   Products, Inc. (IVP, Delaware, USA) and by the Russian Foundation for
   Basic Research (grant 09-04-01071a and Federal Agency for Education
   (State contract P1293). Dr. Mark A. Babizhayev thanks Exsymol SAM
   (Principaute de Monaco) for the provided cooperation in this study. The
   biologically significant applications of carnosine mimetics were
   patented by Dr. Babizhayev and the alliance Groups (WO 2004/028536 A1;
   WO 94/19325; WO 95/12581; WO 2004/064866 A1). IVP Inc. is a
   pharmaceutical and nanotechnology development company with a focus on
   innovative chemical entities, drug delivery systems, and unique medical
   devices to target specific biomedical applications.
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NR 138
TC 11
Z9 12
U1 1
U2 11
PU BEGELL HOUSE INC
PI DANBURY
PA 50 NORTH ST, DANBURY, CT 06810 USA
SN 0743-4863
EI 2162-660X
J9 CRIT REV THER DRUG
JI Crit. Rev. Ther. Drug Carr. Syst.
PY 2010
VL 27
IS 2
BP 85
EP 154
DI 10.1615/CritRevTherDrugCarrierSyst.v27.i2.10
PG 70
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 606MO
UT WOS:000278429300001
PM 20486899
DA 2022-11-30
ER

PT J
AU Zhao, L
   Sweet, BV
AF Zhao, Lili
   Sweet, Burgunda V.
TI Lutein and zeaxanthin for macular degeneration
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Article
DE carotenoids; dietary supplements; geriatrics; lutein; macular
   degeneration; mechanism of action; zeaxanthin
ID PIGMENT OPTICAL-DENSITY; AGE-RELATED MACULOPATHY; EYE DISEASE; DIETARY
   SUPPLEMENTATION; CONSTITUENT CAROTENOIDS; SERUM CONCENTRATIONS; PLASMA
   KINETICS; PROTECTIVE ROLE; RISK-FACTORS; VITAMIN-C
AB Purpose. The effects of increasing lutein and zeaxanthin dosages in people with age-related macular degeneration (AMD) are discussed.
   Summary. AMD is a disorder of the macula, the area associated with the sharpest visual acuity. AMD is classified as dry (nonneovascular) or wet (neovascular) and is associated with several risk factors, the biggest being age. The pathogenesis of AMD is unknown. Like many chronic illnesses, prevention is a key factor for managing AMD. Lutein and zeaxanthin, natural xanthophylls not synthesized by the human body, have been investigated for their use in promoting visual health. Lutein and zeaxanthin are dietary carotenoids that are components of a normal diet. The mechanism of protection that they confer is unknown, but two mechanisms have been hypothesized. Several studies have been conducted to assess the relationship between plasma levels of lutein and zeaxanthin and the risk of developing AMD and have yielded conflicting results. Increased dietary intake of or supplementation with lutein and zeaxanthin was found to result in increased plasma levels, which were positively and significantly associated with macular pigment optical density. Limited data have suggested that supplementation may also improve visual function. The optimal dose of lutein and zeaxanthin for the prevention or treatment of AMD has not yet been defined.
   Conclusion. A definite association between lutein and zeaxanthin supplementation and clinical benefit has yet to be shown; however, it may still be an appropriate cautionary measure for patients at high risk for developing AMD.
C1 [Sweet, Burgunda V.] Univ Michigan Hosp & Hlth Ctr, Ann Arbor, MI 48019 USA.
   [Zhao, Lili; Sweet, Burgunda V.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan; University of
   Michigan System; University of Michigan
RP Sweet, BV (通讯作者)，Univ Michigan Hosp & Hlth Ctr, UHB2D301,Box 5008,1500 E Med Ctr Dr, Ann Arbor, MI 48019 USA.
EM gsweet@umich.edu
OI Sweet, Burgunda/0000-0002-2106-771X
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   LUTEIN ZEAXANTHIN PR
NR 54
TC 34
Z9 37
U1 3
U2 31
PU AMER SOC HEALTH-SYSTEM PHARMACISTS
PI BETHESDA
PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA
SN 1079-2082
J9 AM J HEALTH-SYST PH
JI Am. J. Health-Syst. Pharm.
PD JUL 1
PY 2008
VL 65
IS 13
BP 1232
EP 1238
DI 10.2146/ahjp080052
PG 7
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 318YW
UT WOS:000257129700009
PM 18574012
DA 2022-11-30
ER

PT J
AU Schaumberg, DA
   Christen, WG
   Buring, JE
   Glynn, RJ
   Rifai, N
   Ridker, PM
AF Schaumberg, Debra A.
   Christen, William G.
   Buring, Julie E.
   Glynn, Robert J.
   Rifai, Nader
   Ridker, Paul M.
TI High-sensitivity C-reactive protein, other markers of inflammation, and
   the incidence of macular degeneration in women
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; AGE-RELATED MACULOPATHY; PUBLIC-HEALTH PRACTICE;
   CARDIOVASCULAR-DISEASE; RISK-FACTORS; BRUCHS MEMBRANE; Y402H VARIANT;
   DRUSEN; SUSCEPTIBILITY; POLYMORPHISM
AB Objective: To investigate whether high-sensitivity C-reactive protein (hsCRP) and other biomarkers of inflammation predict age-related macular degeneration (AMD).
   Methods: We measured hsCRP, soluble intercellular adhesion molecule-1 (sICAM-1), and fibrinogen levels in baseline plasma samples from 27 687 participants with a mean age of 54.6 years and initially free of AMD in the Women's Health Study. We prospectively ascertained 150 cases of AMD with vision loss of 20/30 or worse in the affected eye by self-report confirmed with review of medical records during 275 852 person-years of follow-up (mean=10 years) and used proportional hazards models to examine the relationship between these biomarkers and AMD.
   Results: After adjustment for multiple risk factors, the hazard ratio (HR) (95% confidence interval [ CI]) of AMD, contrasting the highest vs lowest quintile of hsCRP, was 3.09 (1.39-6.88) ( P trend=.02). In similar models, the HR( 95% CI) for sICAM-1 was 1.87 (0.97-3.58) ( P trend=.07). The relationship between fibrinogen and AMD was J-shaped, with an HR ( 95% CI) of 2.01 (1.07-3.75) for women in the highest fifth vs second fifth.
   Conclusion: Elevated circulating levels of hsCRP, sI-CAM-1, and fibrinogen precede the development of visually significant AMD in women, providing further support for the hypothesis that inflammation may play a role in AMD.
C1 Div Prevent Med, Boston, MA 02215 USA.
   Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
   Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA.
   Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA.
   Childrens Hosp, Schepens Eye Res Inst, Boston, MA 02115 USA.
C3 Harvard University; Brigham & Women's Hospital; Harvard University;
   Harvard Medical School; Harvard University; Harvard Medical School;
   Harvard University; Boston Children's Hospital; Harvard University;
   Boston Children's Hospital; Schepens Eye Research Institute
RP Schaumberg, DA (通讯作者)，Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA.
EM dschaumberg@rics.bwh.harvard.edu
FU NATIONAL CANCER INSTITUTE [R01CA047988] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R01EY006633, R01EY013834, K23EY000365,
   R01EY017362] Funding Source: NIH RePORTER; NATIONAL HEART, LUNG, AND
   BLOOD INSTITUTE [R01HL043851] Funding Source: NIH RePORTER; NCI NIH HHS
   [CA47988, R01 CA047988] Funding Source: Medline; NEI NIH HHS [R01
   EY013834-02, R01 EY013834-01A1, K23 EY000365-04, EY06633, R01 EY017362,
   R01 EY017362-01A2, K23 EY000365-05, R01 EY013834-03, EY013834, R01
   EY013834] Funding Source: Medline; NHLBI NIH HHS [R01 HL043851, HL43851]
   Funding Source: Medline
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NR 55
TC 63
Z9 66
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 MAR
PY 2007
VL 125
IS 3
BP 300
EP 305
DI 10.1001/archopht.125.3.300
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 145DR
UT WOS:000244846000001
PM 17353399
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Jeppesen, P
   Bek, T
AF Jeppesen, P
   Bek, T
TI The occurrence and causes of registered blindness in diabetes patients
   in Arhus County, Denmark
SO ACTA OPHTHALMOLOGICA SCANDINAVICA
LA English
DT Article
DE diabetic retinopathy; epidemiology; diabetes mellitus; blindness;
   diabetic maculopathy; proliferative diabetic retinopathy; social
   blindness; legal blindness
ID VISUAL IMPAIRMENT; EYE DISEASE; PREVALENCE; TYPE-2; POPULATION;
   MELLITUS; ACUITY; RISK; RETINOPATHY; VISION
AB Purpose: To report the occurrence of registered blindness among diabetes patients in Arhus County, Denmark during 1993-2002.
   Methods: Data were obtained from a database of 7527 diabetes patients, which included all patients in the county who had been treated for or had experienced visual loss due to diabetic retinopathy since 1992. Of these, 1949 had type 1 diabetes and represented 90% of the type 1 diabetes patient population in the county, and 5459 had type 2 diabetes and represented 40% of the type 2 diabetes patient population in the county.
   Results: The point prevalence of legal blindness was 0.6% for type 1 and 1.5% for type 2 diabetes patients at January 1st, 2003. In type 1 diabetes patients, the major cause of blindness was proliferative diabetic retinopathy (PDR) (66.2% of all blind eyes); in type 2 diabetes patients the major causes were age-related macular degeneration (21.9%), PDR (18.0%) and diabetic maculopathy (DMac) (18.5%). During 1993-2002 there was a significant decrease in the number of blind eyes secondary to PDR (p = 0.008) in type 1 diabetes patients, and a significant increase in the number of blind eyes secondary to DMac (p = 0.005) in type 2 diabetes patients.
   Conclusion: The major challenge in reducing diabetes-related blindness is related to the detection and treatment of an increased incidence of diabetic maculopathy in type 2 diabetes patients.
C1 Aarhus Univ Hosp, Dept Ophthalmol, DK-8000 Aarhus C, Denmark.
C3 Aarhus University
RP Jeppesen, P (通讯作者)，Aarhus Univ Hosp, Dept Ophthalmol, Norrebrogade 44, DK-8000 Aarhus C, Denmark.
EM pj@dadlnet.dk
OI Bek, Toke/0000-0002-0409-2534; Jeppesen, Peter/0000-0001-6400-0833
CR Attebo K, 1998, OPHTHALMOLOGY, V105, P154, DOI 10.1016/S0161-6420(98)91862-0
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NR 27
TC 35
Z9 40
U1 0
U2 1
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 OCT
PY 2004
VL 82
IS 5
BP 526
EP 530
DI 10.1111/j.1600-0420.2004.00313.x
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 858DE
UT WOS:000224169700005
PM 15453847
OA Bronze
DA 2022-11-30
ER

PT J
AU Lane, SS
   Kuppermann, BD
   Fine, IH
   Hamill, MB
   Gordon, JF
   Chuck, RS
   Hoffman, RS
   Packer, M
   Koch, DD
AF Lane, SS
   Kuppermann, BD
   Fine, IH
   Hamill, MB
   Gordon, JF
   Chuck, RS
   Hoffman, RS
   Packer, M
   Koch, DD
TI A prospective multicenter clinical trial to evaluate the safety and
   effectiveness of the implantable miniature telescope
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; CATARACT; LENS
AB PURPOSE: To evaluate the safety and preliminary efficacy of a novel visual prosthetic device, the Implantable Miniature Telescope, IMT (by Dr Isaac Lipshitz) (IMT), in a phase I trial in patients with significant bilateral central vision impairment from late-stage age-related macular degeneration (AMD). The IMT is designed to reduce the relative size of the scotoma by rendering enlarged (threefold) central visual field images over the central and peripheral retina.
   DESIGN: Prospective, multicenter, open,label clinical trial.
   METHODS: In this prospective, multicenter phase I trial, 14 patients aged 60 or older with bilateral geographic atrophy or disciform scar AMD, cataract, and best,corrected visual acuity (BCVA) between 20/80 and 20/400 had an IMT implanted in one eye. Distance and near BCVA, endothelial cell density, and quality of life, measured as activities of daily life (ADL), were evaluated preoperatively and postoperatively.
   RESULTS: At 12 months, 10 (77%) of 13 patients gained 2 more lines of either distance or near BCVA, and eight (62%) of 13 patients gained 3 or more lines in either distance or near BCVA. Mean endothelial cell density decreased by 13%. All adverse events resolved without sequelae. ADL scores improved in the majority of patients.
   CONCLUSION: The results of this phase I trial support further evaluation of the IMT in a larger study population with late-stage AMD. A phase II/III trial is in progress. (C) 2004 by Elsevier Inc. All rights reserved.
C1 Univ Calif Irvine, Dept Ophthalmol, Irvine, CA 92697 USA.
   Associated Eye Care, Stillwater, MN USA.
   Oregon Hlth & Sci Univ, Dept Ophthalmol, Eugene, OR USA.
   Baylor Coll Med, Cullen Eye Inst, Dept Ophthalmol, Houston, TX 77030 USA.
   ClinReg Consulting Serv Inc, Irvine, CA USA.
C3 University of California System; University of California Irvine; Oregon
   Health & Science University; Baylor College of Medicine
RP Kuppermann, BD (通讯作者)，Univ Calif Irvine, Dept Ophthalmol, 118 MedSurge 1, Irvine, CA 92697 USA.
EM bdkupper@uci.edu
RI Packer, Mark/P-8600-2019
OI Packer, Mark/0000-0003-2681-6641
CR Beltrame G, 2002, J CATARACT REFR SURG, V28, P118, DOI 10.1016/S0886-3350(01)00983-X
   CHENG H, 1986, ARCH OPHTHALMOL-CHIC, V104, P1170
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   Wang JJ, 1998, BRIT J OPHTHALMOL, V82, P743, DOI 10.1136/bjo.82.7.743
NR 12
TC 35
Z9 37
U1 0
U2 8
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 JUN
PY 2004
VL 137
IS 6
BP 993
EP 1001
DI 10.1016/j.ajo.2004.01.030
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 828YV
UT WOS:000222010600003
PM 15183782
DA 2022-11-30
ER

PT J
AU Nakamura, S
   Nishinaka, A
   Hidaka, Y
   Shimazawa, M
   Thomas, L
   Bakker, RA
   Hara, H
AF Nakamura, Shinsuke
   Nishinaka, Anri
   Hidaka, Yae
   Shimazawa, Masamitsu
   Thomas, Leo
   Bakker, Remko A.
   Hara, Hideaki
TI Efficacy of an Anti-Semaphorin 3A Neutralizing Antibody in a Male
   Experimental Retinal Vein Occlusion Mouse Model
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE diabetic macular ischemia; diabetic macular edema; diabetic retinopathy;
   retinal vein occlusion; Sema3A
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR EDEMA; GANGLION-CELLS; TNF-ALPHA;
   VASCULAR-PERMEABILITY; DIABETIC-RETINOPATHY; BRAIN; DEATH; AREAS; VEGF
AB PURPOSE. Semaphorin 3A (Sema3A) is a promising therapeutic target for macular edema in age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion (RVO). Anti-vascular endothelial growth factors (anti-VEGFs) are the current standard of care for many retinal diseases. This study investigated the Sema3A neutralizing antibody BI-X and/or anti-VEGF therapy (aflibercept) in an RVO mouse model. Treatment efficacy was examined and grouped by timing subsequent to the RVO mouse model induction: efficacy against the onset of intraretinal edema 1 day postinduction and protective effects at 7 days postinduction.
   METHODS. We examined the changes in expression of Sema3A in the retina of an RVO mouse model. In addition, changes in expression of tumor necrosis factor (TNF)-alpha and semaphorin-related proteins (neuropilin-1 and plexin A1) in the retina upon treatment were analyzed by Western blotting. The effects of BI-X and/or aflibercept were evaluated using measures of retinal edema, blood flow, and thinning of the inner nuclear layer.
   RESULTS. Induction of vein occlusion in the RVO mouse model significantly increased Sema3A expression in the retina, particularly in the inner nuclear layer. BI-X was effective as a monotherapy and in combination with anti-VEGF therapy, demonstrating a beneficial effect on intraretinal edema and retinal blood flow. Moreover, in the RVO mouse model, BI-X monotherapy normalized the changes in expression of TNF-alpha and semaphorinrelated proteins.
   CONCLUSIONS. These findings support targeting Sema3A to treat intraretinal edema and retinal ischemia.
C1 [Nakamura, Shinsuke; Nishinaka, Anri; Hidaka, Yae; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, Gifu, Japan.
   [Thomas, Leo; Bakker, Remko A.] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
C3 Gifu Pharmaceutical University; Boehringer Ingelheim
RP Hara, H (通讯作者)，Gifu Pharmaceut Univ, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
EM hidehara@gifu-pu.ac.jp
FU OPEN Health Communications (London, UK) - Boehringer Ingelheim
FX Editorial support in the preparation of this manuscript was provided by
   OPEN Health Communications (London, UK) and funded by Boehringer
   Ingelheim.
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NR 39
TC 1
Z9 1
U1 2
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 JUL
PY 2022
VL 63
IS 8
AR 14
DI 10.1167/iovs.63.8.14
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3F3MY
UT WOS:000830575900006
PM 35822950
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Rosmus, DD
   Lange, C
   Ludwig, F
   Ajami, B
   Wieghofer, P
AF Rosmus, Dennis-Dominik
   Lange, Clemens
   Ludwig, Franziska
   Ajami, Bahareh
   Wieghofer, Peter
TI The Role of Osteopontin in Microglia Biology: Current Concepts and
   Future Perspectives
SO BIOMEDICINES
LA English
DT Review
DE microglia; macrophages; osteopontin; SPP1; inflammation;
   neurodegeneration; multiple sclerosis; Alzheimer's disease; AMD; retina;
   CNS
ID AMYOTROPHIC-LATERAL-SCLEROSIS; EXPERIMENTAL AUTOIMMUNE
   ENCEPHALOMYELITIS; INDUCED CHOROIDAL NEOVASCULARIZATION; MOTOR-NEURON
   DEGENERATION; NF-KAPPA-B; ALZHEIMERS-DISEASE; MACULAR DEGENERATION;
   PROINFLAMMATORY CYTOKINE; DIABETIC-RETINOPATHY; PLASMA OSTEOPONTIN
AB The innate immune landscape of the central nervous system (CNS), including the brain and the retina, consists of different myeloid cell populations with distinct tasks to fulfill. Whereas the CNS borders harbor extraparenchymal CNS-associated macrophages whose main duty is to build up a defense against invading pathogens and other damaging factors from the periphery, the resident immune cells of the CNS parenchyma and the retina, microglia, are highly dynamic cells with a plethora of functions during homeostasis and disease. Therefore, microglia are constantly sensing their environment and closely interacting with surrounding cells, which is in part mediated by soluble factors. One of these factors is Osteopontin (OPN), a multifunctional protein that is produced by different cell types in the CNS, including microglia, and is upregulated in neurodegenerative and neuroinflammatory conditions. In this review, we discuss the current literature about the interaction between microglia and OPN in homeostasis and several disease entities, including multiple sclerosis (MS), Alzheimer's and cerebrovascular diseases (AD, CVD), amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD) and diabetic retinopathy (DR), in the context of the molecular pathways involved in OPN signaling shaping the function of microglia. As nearly all CNS diseases are characterized by pathological alterations in microglial cells, accompanied by the disturbance of the homeostatic microglia phenotype, the emergence of disease-associated microglia (DAM) states and their interplay with factors shaping the DAM-signature, such as OPN, is of great interest for therapeutical interventions in the future.
C1 [Rosmus, Dennis-Dominik; Wieghofer, Peter] Univ Leipzig, Inst Anat, D-04103 Leipzig, Germany.
   [Lange, Clemens; Ludwig, Franziska] Univ Freiburg, Freiburg Med Ctr, Eye Ctr, D-79106 Freiburg, Germany.
   [Lange, Clemens] St Franziskus Hosp, Dept Ophthalmol, Ophtha Lab, D-48145 Munster, Germany.
   [Ajami, Bahareh] Oregon Hlth & Sci Univ, Dept Microbiol & Immunol, Portland, OR 97239 USA.
   [Wieghofer, Peter] Augsburg Univ, Med Fac, Inst Theoret Med, Cellular Neuroanat, D-86159 Augsburg, Germany.
C3 Leipzig University; University of Freiburg; St. Franziskus-Hospital;
   Oregon Health & Science University
RP Wieghofer, P (通讯作者)，Univ Leipzig, Inst Anat, D-04103 Leipzig, Germany.; Wieghofer, P (通讯作者)，Augsburg Univ, Med Fac, Inst Theoret Med, Cellular Neuroanat, D-86159 Augsburg, Germany.
EM dennis-dominik.rosmus@medizin.uni-leipzig.de;
   clemens.lange@augen-franziskus.de;
   franziska.ludwig@uniklinik-freiburg.de; ajami@ohsu.edu;
   peter.wieghofer@med.uni-augsburg.de
RI Wieghofer, Peter/AAV-9572-2020
OI Lange, Clemens/0000-0002-2580-6823; Rosmus,
   Dennis-Dominik/0000-0002-4094-0334
FU German Academic Scholarship Foundation; German Ophthalmological Society
FX D.-D.R. was supported by scholarships provided by the German Academic
   Scholarship Foundation and the German Ophthalmological Society. All
   figures were created with Biorender.com.
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NR 253
TC 2
Z9 2
U1 2
U2 5
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2227-9059
J9 BIOMEDICINES
JI Biomedicines
PD APR
PY 2022
VL 10
IS 4
AR 840
DI 10.3390/biomedicines10040840
PG 31
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental;
   Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Research & Experimental Medicine;
   Pharmacology & Pharmacy
GA 0S5PV
UT WOS:000786326400001
PM 35453590
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Altay, L
   Liakopoulos, S
   Berghold, A
   Rosenberger, KD
   Ernst, A
   De Breuk, A
   Den Hollander, AI
   Fauser, S
   Schick, T
AF Altay, Lebriz
   Liakopoulos, Sandra
   Berghold, Aileen
   Rosenberger, Kerstin-Daniela
   Ernst, Angela
   de Breuk, Anita
   den Hollander, Anneke, I
   Fauser, Sascha
   Schick, Tina
TI Genetic and environmental risk factors for reticular pseudodrusen in the
   EUGENDA study
SO MOLECULAR VISION
LA English
DT Article
ID SUBRETINAL DRUSENOID DEPOSITS; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; GEOGRAPHIC ATROPHY; ASSOCIATION; PREVALENCE; MEMBRANE;
   VARIANT; RARE
AB Purpose: The purpose of this study was to analyze genetic and nongenetic associations with reticular pseudodrusen (RPD) in patients with and without age-related macular degeneration (AMD).
   Methods: This case-control study included 2,719 consecutive subjects from the prospective multicenter European Genetic Database (EUGENDA). Color fundus photographs and optical coherence tomography (OCT) scans were evaluated for the presence of AMD and RPD. Association of RPD with 39 known AMD polymorphisms and various nongenetic risk factors was evaluated. Stepwise backward variable selection via generalized linear models (GLMs) was performed based on models including the following: a) age, sex, and genetic factors and b) all predictors. Receiver operating characteristic (ROC) curves and the areas under the curve (AUCs) were determined.
   Results: RPD were present in 262 cases (no AMD, n = 9 [0.7%; early/intermediate AMD, n = 75 [12.4%]; late AMD, n = 178 [23.8%]). ROC analysis of the genetic model including age, APOE rs2075650, ARMS2 rs10490924, CFH rs800292, CFH rs12144939, CFI rs10033900, COL8A1 rs13081855, COL10A1 rs3812111, GLI3 rs2049622, and SKIV2L rs4296082 revealed an AUC of 0.871. Considering all possible predictors, backward selection revealed a slightly different set of genetic factors, as well as the following nongenetic risk factors: smoking, rheumatoid arthritis, steroids, antiglaucomatous drugs, and past sunlight exposure; the results showed an AUC of 0.886.
   Conclusions: RPD share a variety of genetic and nongenetic risk factors with AMD. Future AMD grading systems should integrate RPD as an important risk phenotype.
C1 [Altay, Lebriz; Liakopoulos, Sandra; Berghold, Aileen; Fauser, Sascha; Schick, Tina] Univ Cologne, Fac Med, Dept Ophthalmol, Cologne, Germany.
   [Altay, Lebriz; Liakopoulos, Sandra; Berghold, Aileen; Rosenberger, Kerstin-Daniela; Ernst, Angela; Fauser, Sascha; Schick, Tina] Univ Cologne, Univ Hosp Cologne, Cologne, Germany.
   [Liakopoulos, Sandra; Schick, Tina] Univ Cologne, Fac Med, Cologne Image Reading Ctr, Dept Ophthalmol, Cologne, Germany.
   [Liakopoulos, Sandra] Goethe Univ, Dept Ophthalmol, Frankfurt, Germany.
   [Rosenberger, Kerstin-Daniela; Ernst, Angela] Univ Cologne, Med Fac, Inst Med Stat & Computat Biol, Dept Med Stat & Computat Biol, Cologne, Germany.
   [de Breuk, Anita; den Hollander, Anneke, I] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Med Ctr, Nijmegen, Netherlands.
   [de Breuk, Anita; den Hollander, Anneke, I] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Human Genet, Med Ctr, Nijmegen, Netherlands.
   [Fauser, Sascha] F Hoffmann La Roche & Cie AG, Basel, Switzerland.
   [Schick, Tina] MVZ Augenarztl Diagnost & Therapiectr Siegburg Gm, AugenZentrum Siegburg, Siegburg, Germany.
C3 University of Cologne; University of Cologne; University of Cologne;
   Goethe University Frankfurt; University of Cologne; Radboud University
   Nijmegen; Radboud University Nijmegen; Roche Holding
RP Liakopoulos, S (通讯作者)，Univ Hosp Cologne, Cologne Image Reading Ctr, Dept Ophthalmol, Kerpenerstr 62, D-50924 Cologne, Germany.
EM sandra.liakopoulos@uk-koeln.de
OI Ernst, Angela/0000-0003-2375-1889
FU German Research Foundation DFG [FOR 2240]; European Research Council
   under the European Union's Seventh Framework Program (FP/2007-2013)/ERC
   Grant [310,644]
FX The research leading to these results has received funding from the
   German Research Foundation DFG FOR 2240 and the European Research
   Council under the European Union's Seventh Framework Program
   (FP/2007-2013)/ERC Grant Agreement n. 310,644 (MACULA). Conflicts of
   interest: S.L. reports lecture fees from Heidelberg Engineering and Carl
   Zeiss Meditec outside of the study. T.S. has received speaker honoraria
   from Bayer and Novartis and has served on an advisory board for Allergan
   without relation to the presented work.
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NR 46
TC 0
Z9 0
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 DEC 31
PY 2021
VL 27
BP 766
EP 776
PG 11
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA YD0AT
UT WOS:000740045200001
PM 35136347
DA 2022-11-30
ER

PT J
AU Hacker, V
   Reiter, GS
   Schranz, M
   Told, R
   Reumuller, A
   Hofer, D
   Steiner, I
   Schmidt-Erfurth, U
   Sacu, S
AF Hacker, Valentin
   Reiter, Gregor Sebastian
   Schranz, Markus
   Told, Reinhard
   Reumueller, Adrian
   Hofer, Dominik
   Steiner, Irene
   Schmidt-Erfurth, Ursula
   Sacu, Stefan
TI Impact of large choroidal vessels on choriocapillaris flow deficit
   analyses in optical coherence tomography angiography
SO PLOS ONE
LA English
DT Article
AB Purpose To investigate the impact of large choroidal vessels (LCV) on Choriocapillaris (CC) flow deficit (FD) analyses with swept-source optical coherence tomography angiography (SS-OCTA) Design Prospective, cross-sectional study. Methods Macular 6x6mm SS-OCTA scans were obtained from intermediate age-related macular degeneration (iAMD) and healthy eyes. Images were captured and processed according to most common standards and analyzed for percentage of flow-deficits (FD%) within four 1x1mm squares at the corners of each image. Choroidal thickness (CT), iris color and refraction error were considered as potential influential factors for LCV visibility. A linear mixed model and logistic regression models were calculated for statistical evaluation. Results Sixty-nine iAMD and 49 age-matched healthy eyes were enrolled. LCV were visible in at least one sector in 52% of iAMD and 47% of healthy eyes. Within the iAMD group FD% were significantly lower in areas containing LCV (p = 0.0029). Increasing CT resulted in an odds ratio decrease of LCV (OR: 0.94, p<0.0001). Below a CT value of <= 118 mu m LCV could be expected with a sensitivity of 86% and a specificity of 85%. Conclusions LCV can significantly affect CC FD analyses of SS-OCTA images. Their visibility is negatively associated with CT. The impact of LCV should be taken into account when performing CC FD assessments, especially in patients where reduced CT is to be expected and inclusion of affected areas should be considered carefully.
C1 [Hacker, Valentin; Schranz, Markus; Told, Reinhard; Reumueller, Adrian; Schmidt-Erfurth, Ursula; Sacu, Stefan] Med Univ Vienna, Dept Ophthalmol & Optomet, Vienna Clin Trial Ctr VTC, Vienna, Austria.
   [Reiter, Gregor Sebastian; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol & Optomet, Vienna Reading Ctr, Christian Doppler Lab Ophthalm Image Anal, Vienna, Austria.
   [Hofer, Dominik; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol & Optomet, Vienna Reading Ctr VRC, Vienna, Austria.
   [Steiner, Irene] Med Univ Vienna, Sect Med Stat, Ctr Med Stat Informat & Intelligent Syst, Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna; Medical
   University of Vienna; Medical University of Vienna
RP Sacu, S (通讯作者)，Med Univ Vienna, Dept Ophthalmol & Optomet, Vienna Clin Trial Ctr VTC, Vienna, Austria.
EM Stefan.sacu@meduniwien.ac.at
OI Hacker, Valentin/0000-0003-0046-5804; Schranz,
   Markus/0000-0002-2630-1368; Reiter, Gregor/0000-0001-7661-4015; Told,
   Reinhard/0000-0003-2046-7081
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NR 28
TC 0
Z9 0
U1 1
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 AUG 3
PY 2021
VL 16
IS 8
AR e0254955
DI 10.1371/journal.pone.0254955
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA UA6IR
UT WOS:000685264200022
PM 34343177
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Oh, JK
   de Carvalho, JRL
   Nuzbrokh, Y
   Ryu, J
   Chemudupati, T
   Mahajan, VB
   Sparrow, JR
   Tsang, SH
AF Oh, Jin Kyun
   de Carvalho, Jose Ronaldo Lima, Jr.
   Nuzbrokh, Yan
   Ryu, Joseph
   Chemudupati, Teja
   Mahajan, Vinit B.
   Sparrow, Janet R.
   Tsang, Stephen H.
TI Retinal Manifestations of Mitochondrial Oxidative Phosphorylation
   Disorders
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE mitochondria; retinal pigment epithelium; inherited retinal degeneration
ID FUNDUS AUTOFLUORESCENCE; PIGMENT EPITHELIUM; CONGENITAL-RUBELLA; OUTER;
   CHOROIDEREMIA; TUBULATION; DEGENERATION; DAMAGE; HISTOPATHOLOGY;
   DYSFUNCTION
AB PURPOSE. The purpose of this paper was to discuss manifestations of primary mitochondrial dysfunctions and whether the retinal pigment epithelium or the photoreceptors are preferentially affected.
   METHODS. A retrospective analysis was performed of patients with clinically and laboratory confirmed diagnoses of maternally inherited diabetes and deafness (MIDD) or Kearns-Sayre syndrome (KSS). Patients underwent full ophthalmic examination, full-field electroretinogram, and multimodal imaging studies, including short-wavelength autofluorescence, spectral domain-optical coherence tomography, and color fundus photography.
   RESULTS. A total of five patients with MIDD and four patients with KSS were evaluated at two tertiary referral centers. Mean age at initial evaluation was 50.3 years old. Nascent outer retinal tubulations corresponding with faint foci of autofluorescence were observed in two patients with MIDD. Characteristic features of this cohort included a foveal sparing phenotype observed in 13 of 18 eyes (72%), global absence of intraretinal pigment migration, and preserved retinal function on full-field electroretinogram testing in 12 of 16 eyes (75%). One patient diagnosed with MIDD presented with an unusual pattern of atrophy surrounding the parapapillary region and one patient with KSS presented with an atypical choroideremia-like phenotype.
   CONCLUSIONS. MIDD and KSS are phenotypically heterogeneous disorders. Several features of disease suggest that primary mitochondrial dysfunction may first affect the retinal pigment epithelium followed by secondary photoreceptor loss. Similarities between primary mitochondrial degenerations and retinal disorders, such as age-related macular degeneration may suggest a primary role of mitochondria in the pathogenesis of these oligogenic disorders.
C1 [Oh, Jin Kyun; de Carvalho, Jose Ronaldo Lima, Jr.; Nuzbrokh, Yan; Ryu, Joseph; Sparrow, Janet R.; Tsang, Stephen H.] Columbia Univ, Dept Ophthalmol, Jonas Childrens Vis Care, Irving Med Ctr, New York, NY 10032 USA.
   [Oh, Jin Kyun] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
   [de Carvalho, Jose Ronaldo Lima, Jr.] Fed Univ Pernambuco UFPE, Empresa Brasileira Serv Hosp EBSERH, Dept Ophthalmol, Hosp Clin Pernambuco HCPE, Recife, PE, Brazil.
   [de Carvalho, Jose Ronaldo Lima, Jr.] Fed Univ Sao Paulo UNIFESP, Dept Ophthalmol, Sao Paulo, SP, Brazil.
   [Nuzbrokh, Yan] SUNY Stony Brook, Renaissance Sch Med, Stony Brook, NY 11794 USA.
   [Chemudupati, Teja; Mahajan, Vinit B.] Stanford Univ, Mol Surg Lab, Byers Eye Inst, Palo Alto, CA 94304 USA.
   [Mahajan, Vinit B.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA.
   [Sparrow, Janet R.; Tsang, Stephen H.] Columbia Univ, Dept Pathol & Cell Biol, Irving Med Ctr, New York, NY 10032 USA.
   [Sparrow, Janet R.; Tsang, Stephen H.] Columbia Univ, CSCI, Irving Med Ctr, New York, NY 10032 USA.
C3 Columbia University; NewYork-Presbyterian Hospital; State University of
   New York (SUNY) System; State University of New York (SUNY) Downstate
   Medical Center; Universidade Federal de Pernambuco; Universidade Federal
   de Sao Paulo (UNIFESP); State University of New York (SUNY) System; SUNY
   Community College; State University of New York (SUNY) Stony Brook;
   Stony Brook University Hospital; Stanford University; US Department of
   Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto
   Health Care System; Columbia University; NewYork-Presbyterian Hospital;
   Columbia University; NewYork-Presbyterian Hospital
RP Tsang, SH (通讯作者)，Columbia Univ, Med Ctr, Harkness Eye Inst, 635 West 165th St,Box 112, New York, NY 10032 USA.
EM sht2@cumc.columbia.edu
OI Ryu, Joseph/0000-0001-5449-2395; Oh, Jin Kyun/0000-0002-5350-9412
FU National Institute of Health [5P30CA013696, U01EY030580, U54OD020351,
   R24EY028758, R24EY027285, 5P30EY019007, R01EY018213, R01EY024698,
   R01EY024091, R01EY026682, R21AG050437]; Schneeweiss Stem Cell Fund, New
   York State [SDHDOH01-C32590GG-3450000]; Foundation Fighting Blindness
   New York Regional Research Center Grant [PPA-1218-0751-COLU]; Crowley
   Family Funds; Rosenbaum Family Foundation; Alcon Research Institute;
   Gebroe Family Foundation; Research to Prevent Blindness (RPB)
   Physician-Scientist Award; RPB, New York, NY, USA; NIH [R01EY EY026877,
   R01EY025225, P30EY026877]; Research to Prevent Blindness, New York, NY,
   USA
FX The Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma
   Laboratory are supported by the National Institute of Health
   5P30CA013696, U01EY030580, U54OD020351, R24EY028758, R24EY027285,
   5P30EY019007, R01EY018213, R01EY024698, R01EY024091, R01EY026682, and
   R21AG050437, the Schneeweiss Stem Cell Fund, New York State
   (SDHDOH01-C32590GG-3450000), the Foundation Fighting Blindness New York
   Regional Research Center Grant (PPA-1218-0751-COLU), Nancy & Kobi Karp,
   the Crowley Family Funds, The Rosenbaum Family Foundation, Alcon
   Research Institute, the Gebroe Family Foundation, the Research to
   Prevent Blindness (RPB) Physician-Scientist Award, unrestricted funds
   from RPB, New York, NY, USA. V.B.M. is supported by NIH Grants (R01EY
   EY026877, R01EY025225, and P30EY026877) and Research to Prevent
   Blindness, New York, NY, USA. The sponsor or funding organization had no
   role in the design or conduct of this research.
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NR 57
TC 6
Z9 6
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 OCT
PY 2020
VL 61
IS 12
AR 12
DI 10.1167/iovs.61.12.12
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OR2IJ
UT WOS:000589298400004
PM 33049060
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ikonne, EU
   Ikpeazu, VO
   Ugbogu, EA
AF Ikonne, Eleazar Uchenna
   Ikpeazu, Victor Okezie
   Ugbogu, Eziuche Amadike
TI The potential health benefits of dietary natural plant products in age
   related eye diseases
SO HELIYON
LA English
DT Review
DE Natural plant products; Oxidative stress; Antioxidant;
   Anti-inflammatory; Eye diseases; Food science; Agricultural science;
   Biological sciences; Veterinary medicine; Health sciences
ID INDUCED RETINAL DEGENERATION; PIGMENT EPITHELIAL-CELLS; OXIDATIVE
   STRESS; EPIGALLOCATECHIN-GALLATE; MACULAR DEGENERATION; RISK-FACTORS;
   VITAMIN-E; OCULAR NEOVASCULARIZATION; INDUCED CATARACTOGENESIS;
   RESVERATROL PREVENTS
AB In the past decade, there has been a tremendous increase in the number of cases of age-related eye diseases such as age-related macular degeneration (AMD), cataract, diabetic retinopathy and glaucoma. These diseases are the leading causes of visual impairment and blindness all over the world and are associated with many pathological risk factors such as aging, pollution, high levels of glucose (hyperglycaemia), high metabolic rates, and light exposure. These risk factors lead to the generation of uncontrollable reactive oxygen species (ROS), which causes oxidative stress. Oxidative stress plays a crucial role in the pathogenesis of age-related eye diseases through the activation of nuclear factor kappa B (NF-kappa B), vascular endothelial growth factor (VEGF), and lipid peroxidation, which leads to the production of inflammatory cytokines, angiogenesis, protein and DNA damages, apoptosis that causes macular degeneration (AMD), cataract, diabetic retinopathy and glaucoma. This review provides updated information on the beneficial effects of dietary natural plant products (DPNPs) against age-related eye diseases. In this review, supplementation of DPNPs demonstrated preventive and therapeutic effects on people at risk of or with age-related eye diseases due to their capacity to scavenge free radicals, ameliorate inflammatory molecules, neutralize the oxidation reaction that occurs in photoreceptor cells, decrease vascular endothelial growth factor and the blood-retinal barrier and increase the antioxidant defence system. However, further experiments and clinical trials are required to establish the daily doses of DPNPs that will safely and effectively prevent age-related eye diseases.
C1 [Ikonne, Eleazar Uchenna] Abia State Univ, Dept Optometry, PMB 2000, Uturu, Abia State, Nigeria.
   [Ikpeazu, Victor Okezie; Ugbogu, Eziuche Amadike] Abia State Univ, Dept Biochem, PMB 2000, Uturu, Abia State, Nigeria.
RP Ugbogu, EA (通讯作者)，Abia State Univ, Dept Biochem, PMB 2000, Uturu, Abia State, Nigeria.
EM amasryal@yahoo.com
RI Ugbogu, Eziuche/AAF-2559-2020; Ugbogu, Eziuche/ABB-8689-2020
OI Ugbogu, Eziuche/0000-0003-3145-5473
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NR 139
TC 10
Z9 10
U1 1
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
EI 2405-8440
J9 HELIYON
JI Heliyon
PD JUL
PY 2020
VL 6
IS 7
AR e04408
DI 10.1016/j.heliyon.2020.e04408
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA MY9KY
UT WOS:000558740000001
PM 32685729
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Chen, QY
   Lin, HM
   Deng, X
   Li, SN
   Zhang, JL
AF Chen, Qianyin
   Lin, Huimin
   Deng, Xuan
   Li, Shengnan
   Zhang, Jinglin
TI MiR-1246 promotes anti-apoptotic effect of mini-alpha A in oxidative
   stress-induced apoptosis in retinal pigment epithelial cells
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE alpha-crystallin; age-related macular degeneration; apoptosis; miR-1246;
   retinal pigment epithelial cell
ID MACULAR DEGENERATION; CRYSTALLIN; MICRORNA-1246; CASPASE-14
AB Background Geographic atrophy (GA) is a late-stage symptom of an age-related macular degeneration (AMD), characterized by the loss of retinal pigment epithelial (RPE) cells and photoreceptor functions. Despite being a major cause of blindness in individuals of 65 years of age and older, some forms of AMD, including GA, still lack targeted treatment. Our previous study demonstrated that mini-alpha A peptide, which contains the functional site of alpha A-crystallin, protected RPE cells from NaIO3-induced apoptosis.
   Methods To further investigate the underlying mechanism, we applied next-generation sequencing analysis to identify miR-1246 as a putative mediator of mini-alpha A protective function. To investigate the role of miR-1246 in RPE cell apoptosis, a stable miR-1246-low-expression cell line was established by using miR-1246 inhibitor. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to investigate the proliferation of RPE cells, mRNA and miR-1246 expression were detected by the quantitative reverse transcriptase-polymerase chain reaction.
   Results We have further identified caspase-3 and caspase-14 as molecular targets of miR-1246 involved in regulation of apoptosis in NaIO3-incubated cells. Interestingly, disruption of miR-1246 expression enhanced anti-apoptotic effect of mini-alpha A on RPE cells during oxidative stress.
   Conclusions Our results provide a mechanistic basis for evaluation of miR-1246 as a new candidate target for the clinical treatment of AMD.
C1 [Chen, Qianyin; Lin, Huimin; Zhang, Jinglin] Aier Eye Hosp Grp, Guangzhou Aier Eye Hosp, Guangzhou, Guangdong, Peoples R China.
   [Deng, Xuan; Li, Shengnan; Zhang, Jinglin] Cent South Univ, Aier Sch Ophthalmol, Changsha, Peoples R China.
C3 Central South University
RP Zhang, JL (通讯作者)，Aier Eye Hosp Grp, Guangzhou Aier Eye Hosp, Guangzhou, Guangdong, Peoples R China.
EM zhjinglin@126.com
FU Science Foundation of Aier Eye Hospital Group [AF2018002]; Natural
   Science Foundation of Hunan Province, China [2019JJ50001]
FX Science Foundation of Aier Eye Hospital Group, Grant/Award Number:
   AF2018002; the Natural Science Foundation of Hunan Province, China,
   Grant/Award Number: 2019JJ50001
CR Al-Shabrawey M, 2012, MOL VIS, V18, P1895
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NR 34
TC 4
Z9 5
U1 0
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1442-6404
EI 1442-9071
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD JUL
PY 2020
VL 48
IS 5
BP 682
EP 688
DI 10.1111/ceo.13751
EA MAR 2020
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MG8KJ
UT WOS:000522504000001
PM 32173992
DA 2022-11-30
ER

PT J
AU Getter, T
   Suh, S
   Hoang, T
   Handa, JT
   Dong, ZQ
   Ma, XL
   Chen, YY
   Blackshaw, S
   Palczewski, K
AF Getter, Tamar
   Suh, Susie
   Thanh Hoang
   Handa, James T.
   Dong, Zhiqian
   Ma, Xiuli
   Chen, Yuanyuan
   Blackshaw, Seth
   Palczewski, Krzysztof
TI The selective estrogen receptor modulator raloxifene mitigates the
   effect of all-trans-retinal toxicity in photoreceptor degeneration
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE retina; vitamin A; vision; retinal degeneration; rhodopsin;
   all-trans-retinal (atRAL); high-throughput screen (HTS); estrogen
   receptor (ER); selective estrogen receptor modulator (SERM);
   photoreceptor degeneration; blindness; cytotoxicity; cell death
ID STARGARDT DISEASE; CALCIUM-UPTAKE; VISUAL CYCLE; ISOMERIZATION;
   PHARMACOLOGY; RAT; EYE; ATP; BIOLUMINESCENCE; IDENTIFICATION
AB The retinoid cycle is a metabolic process in the vertebrate retina that continuously regenerates 11-cis-retinal (11-cisRAL) from the all-trans-retinal (atRAL) isomer. atRAL accumulation can cause photoreceptor degeneration and irreversible visual dysfunction associated with incurable blinding retinal diseases, such as Stargardt disease, retinitis pigmentosa (RP), and atrophic age-related macular degeneration (AMD). The underlying cellular mechanisms leading to retinal degeneration remain uncertain, although previous studies have shown that atRAL promotes calcium influx associated with cell apoptosis. To identify compounds that mitigate the effects of atRAL toxicity, here we developed an unbiased and robust image-based assay that can detect changes in intracellular calcium levels in U2OS cells. Using our assay in a high-throughput screen of 2,400 compounds, we noted that selective estrogen receptor modulators (SERMs) potently stabilize intracellular calcium and thereby counteract atRAL-induced toxicity. In a light-induced retinal degeneration mouse model (Abca4(-/-)Rdh8(-/-)), raloxifene (a benzothiophene-type scaffold SERM) prevented the onset of photoreceptor apoptosis and thus protected the retina from degeneration. The minor structural differences between raloxifene and one of its derivatives (Y 134) had a major impact on calcium homeostasis after atRAL exposure in vitro, and we verified this differential impact in vivo. In summary, the SERM raloxifene has structural and functional neuroprotective effects in the retina. We propose that the highly sensitive image-based assay developed here could be applied for the discovery of additional drug candidates preventing photoreceptor degeneration.
C1 [Getter, Tamar; Suh, Susie; Palczewski, Krzysztof] Univ Calif Irvine, Dept Ophthalmol, Gavin Herbert Eye Inst, Irvine, CA 92697 USA.
   [Getter, Tamar; Suh, Susie; Palczewski, Krzysztof] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA.
   [Thanh Hoang; Blackshaw, Seth] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD 21205 USA.
   [Handa, James T.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Wilmer Eye Inst, Baltimore, MD 21287 USA.
   [Dong, Zhiqian; Ma, Xiuli] Polgenix Inc, Irvine, CA 92617 USA.
   [Chen, Yuanyuan] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15260 USA.
   [Chen, Yuanyuan] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15213 USA.
C3 University of California System; University of California Irvine; Case
   Western Reserve University; Johns Hopkins University; Johns Hopkins
   University; Johns Hopkins Medicine; Pennsylvania Commonwealth System of
   Higher Education (PCSHE); University of Pittsburgh; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); University of
   Pittsburgh
RP Getter, T; Palczewski, K (通讯作者)，Univ Calif Irvine, Dept Ophthalmol, Gavin Herbert Eye Inst, Irvine, CA 92657 USA.
EM tgetter@uci.edu; kpalczew@uci.edu
OI DONG, ZHIQIAN/0000-0002-8748-4532; Chen, Yuanyuan/0000-0001-9625-1610
FU NEI, National Institutes of Health [R24EY024864, R24EY027283, EY024992,
   T32GM007250, F30EY029136-01A1, R01EY027691]; Research to Prevent
   Blindness; Canadian Institute for Advanced Research (CIFAR); Alcon
   Research Institute (ARI); NATIONAL CENTER FOR ADVANCING TRANSLATIONAL
   SCIENCES [TL1TR002549] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [R01EY027691, R24EY024864, F30EY029136, K99EY024992,
   R01EY020560, R24EY027283, R00EY024992] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007250] Funding
   Source: NIH RePORTER
FX This research was supported in part by NEI, National Institutes of
   Health, Grants R24EY024864 and R24EY027283 (to K. P.), EY024992 (to Y.
   C.), T32GM007250 and F30EY029136-01A1 (to S. S.), and R01EY027691 (to J.
   T. H.); an unrestricted grant from Research to Prevent Blindness to the
   Department of Ophthalmology at the University of California (Irvine,
   CA); the Canadian Institute for Advanced Research (CIFAR); and the Alcon
   Research Institute (ARI). K. P. is Chief Scientific Officer at Polgenix,
   Inc. Z. D. and X. M. are employees of Polgenix, Inc. 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 70
TC 5
Z9 5
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI ROCKVILLE
PA 11200 ROCKVILLE PIKE, SUITE 302, ROCKVILLE, MD, UNITED STATES
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 14
PY 2019
VL 294
IS 24
BP 9461
EP 9475
DI 10.1074/jbc.RA119.008697
PG 15
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA IE9QZ
UT WOS:000472713000015
PM 31073029
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Sharma, NK
   Sharma, K
   Singh, R
   Sharma, SK
   Anand, A
AF Sharma, Neel Kamal
   Sharma, Kaushal
   Singh, Ramandeep
   Sharma, Suresh Kumar
   Anand, Akshay
TI CCL2 single nucleotide polymorphism of rs1024611 implicates prominence
   of inflammatory cascade by univariate modeling in Indian AMD
SO PLOS ONE
LA English
DT Article
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHEMOKINE RECEPTOR CX3CR1; GENE
   REGULATORY REGION; MACULAR DEGENERATION; SERUM-LEVELS; DISEASE; RISK
AB Background
   The role of chemotactic protein CCL2/MCP-1 has been widely explored in age related macular degeneration (AMD) patients as well as animal models through our previous studies.
   Aim
   Aim of the study was to examine the association of another variance of CCL2, rs1024611 in pathophysiology of AMD.
   Methods
   This particular SNP has been found to be involved in inflammatory processes in various diseases. Total 171 subjects were recruited in the study with all demographic details by administering a standard questionnaire. SNP analysis was performed with TaqMan assay. Linear univariate and ANCOVA modeling was performed to show the interaction of rs1024611 with another SNP variant of CCL-2/CCR-2 (rs4586 and rs1799865) and impact of individual genotypes on CCL-2 expression in the context of AMD pathology.
   Results
   Results showed that both heterozygous (AG, p = 0.01) and homozygous (GG, p = 0.0001) genotypes are associated with AMD pathology. Allele frequency analysis showed that 'G' allele is frequent in AMD patients as compared to controls (p = 0.0001). Moreover, AMD patients who smoke were found to be associated with 'AG' genotype (p = 0.0145). Although, we did not find any significant interaction between the SNP variants by linear univariate analysis but results show the effect of 'CT' genotype on 'TT' genotype in rs4586 by considering rs1024611 as covariate.
   Conclusion
   Based on these results it is imperative that CCL2 mediated pathology may be associated with AMD.
C1 [Sharma, Neel Kamal; Sharma, Kaushal; Anand, Akshay] Post Grad Inst Med Educ & Res, Dept Neurol, Neurosci Res Lab, Chandigarh, India.
   [Sharma, Neel Kamal] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
   [Sharma, Kaushal; Sharma, Suresh Kumar] Panjab Univ, Ctr Syst Biol & Bioinformat, Chandigarh, India.
   [Singh, Ramandeep] Post Grad Inst Med Educ & Res, Dept Ophthalmol, Chandigarh, India.
   [Sharma, Suresh Kumar] Panjab Univ, Dept Stat, Chandigarh, India.
C3 Post Graduate Institute of Medical Education & Research (PGIMER),
   Chandigarh; National Institutes of Health (NIH) - USA; NIH National Eye
   Institute (NEI); Panjab University; Post Graduate Institute of Medical
   Education & Research (PGIMER), Chandigarh; Panjab University
RP Anand, A (通讯作者)，Post Grad Inst Med Educ & Res, Dept Neurol, Neurosci Res Lab, Chandigarh, India.; Sharma, SK (通讯作者)，Panjab Univ, Ctr Syst Biol & Bioinformat, Chandigarh, India.; Sharma, SK (通讯作者)，Panjab Univ, Dept Stat, Chandigarh, India.
EM ssharma643@yahoo.co.in; akshay1anand@rediffmail.com
RI anand, Akshay/AAI-1586-2019
OI Anand, Akshay/0000-0001-9003-3532
FU Department of Science and Technology, New Delhi, India
   [SR/SO/HS-109/205]
FX Funding was provided by Department of Science and Technology, New Delhi,
   India (F.No. SR/SO/HS-109/205 dated 1-05-2007). Funder had no role in
   study design, data collection and analysis of data.
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NR 29
TC 13
Z9 13
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 APR 17
PY 2018
VL 13
IS 4
AR e0193423
DI 10.1371/journal.pone.0193423
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GD1LV
UT WOS:000430262300004
PM 29664944
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Cheng, J
   Hao, XL
   Zhang, ZC
AF Cheng, Jie
   Hao, Xiaolin
   Zhang, Zhongchen
TI Risk of macular degeneration affected by polymorphisms in Matrix
   metalloproteinase-2 A case-control study in Chinese Han population
SO MEDICINE
LA English
DT Article
DE age; AMD; MMP-2; polymorphisms
ID NEUROMYELITIS-OPTICA; TNF-ALPHA; GENE; MATRIX-METALLOPROTEINASE-9;
   INFECTION; MEMBRANE; VARIANTS; CANCER; MMP-2
AB The purpose of this study was to investigate the correlation of single nucleotide polymorphisms (SNPs) in Matrix metalloproteinase-2 (MMP-2) gene and the risk of age-related macular degeneration (AMD) in Chinese Han population.
   A total of 126 AMD patients and 141 healthy controls participated in this study. Genotypes of MMP-2 gene polymorphisms were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). chi(2) test was used to detect the differences of genotypes and alleles frequencies between case and control groups. Relative risk of AMD was evaluated by odds ratios (ORs) with 95% confidence intervals (CIs).
   Distribution of variant allele carriers (computed tomography+ TT genotypes) of MMP-2 gene rs243865 SNP was significantly different between case and control groups, and might act as protective factors for the onset of AMD (P = .044, OR = 0.583, 95% CI = 0.344-0.987). Nevertheless, the T allele might reduce the AMD risk (P = .030, OR = 0.611, 95% CI = 0.390-0.956). However, no significant association existed between rs243865 and AMD risk in the subgroup analysis based on age. GA+AA genotypes of rs243866 SNP may associate with a decreased risk of AMD in the age <= 65 years subgroup (P = .028, OR = 0.399, 95% CI = 0.174-0.915).
   MMP-2 gene rs243865 and rs243866 SNPs associated with the risk of AMD. Further studies should be performed to confirm the results.
C1 [Cheng, Jie; Hao, Xiaolin; Zhang, Zhongchen] Aerosp Cent Hosp, Dept Ophthalmol, Beijing 100049, Peoples R China.
RP Zhang, ZC (通讯作者)，Aerosp Cent Hosp, Dept Ophthalmol, Beijing 100049, Peoples R China.
EM jkkiwdda@126.com
CR Amin M, 2016, FRONT BIOSCI-LANDMRK, V21, P89, DOI 10.2741/4378
   Berglin L, 2003, INVEST OPHTH VIS SCI, V44, P403, DOI 10.1167/iovs.02-0180
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NR 35
TC 5
Z9 5
U1 0
U2 1
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 NOV
PY 2017
VL 96
IS 47
AR e8190
DI 10.1097/MD.0000000000008190
PG 5
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA FP5FP
UT WOS:000417645700002
PM 29381911
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU van Dijk, EHC
   Tsonaka, R
   Klar-Mohamad, N
   Wouters, D
   de Vries, APJ
   de Jong, EK
   van Kooten, C
   Boon, CJF
AF van Dijk, Elon H. C.
   Tsonaka, Roula
   Klar-Mohamad, Ngaisah
   Wouters, Diana
   de Vries, Aiko P. J.
   de Jong, Eiko K.
   van Kooten, Cees
   Boon, Camiel J. F.
TI Systemic complement activation in central serous chorioretinopathy
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; FACTOR-H; LUPUS-ERYTHEMATOSUS; RISK; POLYMORPHISM;
   VARIANTS; GENE; PATHOPHYSIOLOGY; CORTICOSTEROIDS; PERSPECTIVE
AB Purpose A clear link between several variants in genes involved in the complement system and chronic central serous chorioretinopathy (CSC) has been described. In age-related macular degeneration, a disease that shows clinical features that overlap with CSC, both genetic risk factors and systemic activation of the complement system have previously been found. In this case-control study, we assessed whether there is evidence of either systemic activation or inhibition of the complement system in patients with chronic CSC.
   Methods A prospective case-control study of 76 typical chronic CSC patients and 29 controls without ophthalmological history was conducted. Complement activity assays (classical, alternative, and mannose-binding lectin pathway), complement factors 3, 4, 4A, 4B, B, D, H, I, and P, activation products C3d, C5a, and sC5b-C9, and the C3d/C3 ratio were analysed in either serum or plasma. A correction for possible effects of gender, age, body mass index, and smoking status was performed.
   Results In this study, none of the tested variables, including regulation and activation products, proved to be significantly different between the groups. Moreover, no associations with either CSC disease activity or possible CSC related steroid use were observed.
   Conclusion Despite the available literature regarding a possible relationship between chronic CSC and variants in genes involved in the complement system, we did not find evidence of an association of chronic CSC with either systemic complement activation or inhibition.
C1 [van Dijk, Elon H. C.; Boon, Camiel J. F.] Leiden Univ, Med Ctr, Dept Ophthalmol, Leiden, Netherlands.
   [Tsonaka, Roula] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands.
   [Klar-Mohamad, Ngaisah; van Kooten, Cees] Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
   [Wouters, Diana] Acad Med Ctr, Dept Immunopathol, Sanquin Res, Amsterdam, Netherlands.
   [Wouters, Diana] Acad Med Ctr, Landsteiner Lab, Amsterdam, Netherlands.
   [de Vries, Aiko P. J.] Leiden Univ, Med Ctr, Dept Med, Div Nephrol & Transplantat, Leiden, Netherlands.
   [de Jong, Eiko K.] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.
   [Boon, Camiel J. F.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, Amsterdam, Netherlands.
C3 Leiden University; Leiden University Medical Center (LUMC); Leiden
   University - Excl LUMC; Leiden University; Leiden University Medical
   Center (LUMC); Leiden University - Excl LUMC; Leiden University; Leiden
   University Medical Center (LUMC); Leiden University - Excl LUMC;
   University of Amsterdam; Academic Medical Center Amsterdam; University
   of Amsterdam; Academic Medical Center Amsterdam; Leiden University;
   Leiden University Medical Center (LUMC); Leiden University - Excl LUMC;
   Radboud University Nijmegen; University of Amsterdam; Academic Medical
   Center Amsterdam
RP Boon, CJF (通讯作者)，Leiden Univ, Med Ctr, Dept Ophthalmol, Leiden, Netherlands.; Boon, CJF (通讯作者)，Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, Amsterdam, Netherlands.
EM c.j.f.boon@lumc.nl
RI de Jong, Eiko/P-3407-2015; de Vries, Aiko/J-5397-2015; Boon,
   CJF/P-7534-2014
OI de Jong, Eiko/0000-0001-6520-0407; de Vries, Aiko/0000-0002-9284-3595;
   van Dijk, Elon/0000-0002-6351-7942; Boon, CJF/0000-0002-6737-7932
FU Macula Fonds; Retina Netherlands; Blinden Penning; Landelijke Stichting
   voor Blindenen Slechtzienden; UitZicht; Rotterdamse Stichting
   Blindenbelangen; Haagse Stichting Blindenhulp; ZonMw VENI; GiselaThie
   rFellowship of Leiden University (CJFB)
FX This research was supported by the following foundations: Macula Fonds,
   Retina Netherlands, Blinden Penning, and Landelijke Stichting voor
   Blindenen Slechtzienden, which contributed through UitZicht, as well as
   Rotterdamse Stichting Blindenbelangen, Haagse Stichting Blindenhulp,
   ZonMw VENI Grant, and the GiselaThie rFellowship of Leiden University
   (CJFB). 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 34
TC 6
Z9 6
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 JUL 3
PY 2017
VL 12
IS 7
AR e0180312
DI 10.1371/journal.pone.0180312
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FA2JX
UT WOS:000405268500043
PM 28671968
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Kobayashi, Y
   Yoshida, S
   Zhou, Y
   Nakama, T
   Ishikawa, K
   Kubo, Y
   Arima, M
   Nakao, S
   Hisatomi, T
   Ikeda, Y
   Matsuda, A
   Sonoda, KH
   Ishibashi, T
AF Kobayashi, Yoshiyuki
   Yoshida, Shigeo
   Zhou, Yedi
   Nakama, Takahito
   Ishikawa, Keijiro
   Kubo, Yuki
   Arima, Mitsuru
   Nakao, Shintaro
   Hisatomi, Toshio
   Ikeda, Yasuhiro
   Matsuda, Akira
   Sonoda, Koh-Hei
   Ishibashi, Tatsuro
TI Tenascin-C secreted by transdifferentiated retinal pigment epithelial
   cells promotes choroidal neovascularization via integrin alpha V
SO LABORATORY INVESTIGATION
LA English
DT Article
ID PROLIFERATIVE DIABETIC-RETINOPATHY; MACULAR DEGENERATION; GROWTH-FACTOR;
   FIBROVASCULAR MEMBRANES; EXTRACELLULAR-MATRIX; INCREASED EXPRESSION;
   INTRAVITREAL AFLIBERCEPT; ENDOTHELIAL-CELLS; MESSENGER-RNA; RANIBIZUMAB
AB Tenascin-C is expressed in choroidal neovascular (CNV) membranes in eyes with age-related macular degeneration (AMD). However, its role in the pathogenesis of CNV remains to be elucidated. Here we investigated the role of tenascin-C in CNV formation. In immunofluorescence analyses, tenascin-C co-stained with alpha-SMA, pan-cytokeratin, CD31, CD34, and integrin alpha(V) in the CNV membranes of patients with AMD and a mouse model of laser-induced CNV. A marked increase in the expression of tenascin-C mRNA and protein was observed 3 days after laser photocoagulation in the mouse CNV model. Tenascin-C was also shown to promote proliferation and inhibit adhesion of human retinal pigment epithelial (hRPE) cells in vitro. Moreover, tenascin-C promoted proliferation, adhesion, migration, and tube formation in human microvascular endothelial cells (HMVECs); these functions were, however, blocked by cilengitide, an integrin alpha(V) inhibitor. Exposure to TGF-beta 2 increased tenascin-C expression in hRPE cells. Conditioned media harvested from TGF-beta 2-treated hRPE cell cultures enhanced HMVEC proliferation and tube formation, which were inhibited by pretreatment with tenascin-C siRNA. The CNV volume was significantly reduced in tenascin-C knockout mice and tenascin-C siRNA-injected mice. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of CNV via integrin aV in a paracrine manner. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of CNV development associated with AMD.
C1 [Kobayashi, Yoshiyuki; Yoshida, Shigeo; Zhou, Yedi; Nakama, Takahito; Ishikawa, Keijiro; Kubo, Yuki; Arima, Mitsuru; Nakao, Shintaro; Hisatomi, Toshio; Ikeda, Yasuhiro; Sonoda, Koh-Hei; Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 8128582, Japan.
   [Matsuda, Akira] Juntendo Univ, Dept Ophthalmol, Tokyo, Japan.
C3 Kyushu University; Juntendo University
RP Yoshida, S (通讯作者)，Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 8128582, Japan.
EM yosida@eye.med.kyushu-u.ac.jp
RI Matsuda, Akira/A-9981-2010
OI Matsuda, Akira/0000-0002-0792-3663; Zhou, Yedi/0000-0002-8948-1108;
   Yoshida, Shigeo/0000-0003-1049-8909; Nakama,
   Takahito/0000-0001-8999-3667; Hisatomi, Toshio/0000-0003-2552-9595
FU Japan Society for the Promotion of Science [15H04995, 26293374,
   26670757, 15J03433]
FX The authors would like to thank Masayo Eto for the technical assistance
   provided. This study was supported by Grants-in-Aid for Scientific
   Research (B) (Nos. 15H04995 and 26293374), a Grant-in-Aid for
   Challenging Exploratory Research (No. 26670757), and a Grant-in-Aid for
   JSPS Fellows from Japan Society for the Promotion of Science (No.
   15J03433).
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NR 50
TC 13
Z9 13
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD NOV
PY 2016
VL 96
IS 11
BP 1178
EP 1188
DI 10.1038/labinvest.2016.99
PG 11
WC Medicine, Research & Experimental; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pathology
GA EA1JS
UT WOS:000386349000006
PM 27668890
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Geringswald, F
   Porracin, E
   Pollmann, S
AF Geringswald, Franziska
   Porracin, Eleonora
   Pollmann, Stefan
TI Impairment of visual memory for objects in natural scenes by simulated
   central scotomata
SO JOURNAL OF VISION
LA English
DT Article
DE visual attention; visual long-term memory for objects; simulated
   scotoma; saccadic rereferencing
ID LONG-TERM-MEMORY; FIXATION POSITION; PSYCHOPHYSICS; SACCADE; ATTENTION;
   CAPACITY; TRACKING
AB Because of the close link between foveal vision and the spatial deployment of attention, typically only objects that have been foveated during scene exploration may form detailed and persistent memory representations. In a recent study on patients suffering from age-related macular degeneration, however, we found surprisingly accurate visual long-term memory for objects in scenes. Normal exploration patterns that the patients had learned to rereference saccade targets to an extrafoveal retinal location. This rereferencing may allow use of an extrafoveal location as a focus of attention for efficient object encoding into long-term memory. Here, we tested this hypothesis in normal-sighted observers with gaze-contingent central scotoma simulations. As these observers were inexperienced in scene exploration with central vision loss and had not developed saccadic rereferencing, we expected deficits in long-termmemory for objects. We used the same change detection task as in our patient study, probing sensitivity to object changes after a period of free scene exploration. Change detection performance was significantly reduced for two types of scotoma simulation diminishing foveal and parafoveal vision-a visible gray disc and a more subtle image warping-compared with unimpaired controls, confirming our hypothesis. The impact of a smaller scotoma covering specifically foveal vision was less distinct, leading to a marginally significant decrease of long-term memory performance compared with controls. We conclude that attentive encoding of objects is deficient when central vision is lost as long as successful saccadic rereferencing has not yet developed.
C1 [Geringswald, Franziska; Porracin, Eleonora; Pollmann, Stefan] Univ Magdeburg, Dept Expt Psychol, D-39106 Magdeburg, Germany.
   [Pollmann, Stefan] Ctr Behav Brain Sci, Magdeburg, Germany.
C3 Otto von Guericke University
RP Geringswald, F (通讯作者)，Univ Magdeburg, Inst Psychol 2, D-39106 Magdeburg, Germany.
EM franziska.geringswald@gmail.com
FU Deutsche Forschungsgemeinschaft [PO548/14-1]
FX This work was supported by the Deutsche Forschungsgemeinschaft
   (PO548/14-1). We thank Nico Adelhofer and Marc Rose for assistance in
   data acquisition.
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NR 44
TC 11
Z9 11
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 1534-7362
J9 J VISION
JI J. Vision
PD JAN
PY 2016
VL 16
IS 2
AR 6
DI 10.1167/16.2.6
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA DJ4KW
UT WOS:000374175000006
PM 27002551
OA gold
DA 2022-11-30
ER

PT J
AU Higuchi, H
   Macke, EL
   Lee, WH
   Miller, SA
   Xu, JC
   Ikeda, S
   Ikeda, A
AF Higuchi, Hitoshi
   Macke, Erica L.
   Lee, Wei-Hua
   Miller, Sam A.
   Xu, James C.
   Ikeda, Sakae
   Ikeda, Akihiro
TI Genetic basis of age-dependent synaptic abnormalities in the retina
SO MAMMALIAN GENOME
LA English
DT Article
ID DEGENERATION; STRAINS; NEURONS; TRAITS; STRESS; MICE
AB Understanding the normal aging process will help us determine the mechanisms of how age-related diseases are caused and progress. A/J inbred mice have been shown to exhibit accelerated aging phenotypes in the retina including increased inflammation and photoreceptor cell degeneration, which resemble human aging symptoms. C57BL/6J (B6) inbred mice are less susceptible for these abnormalities, indicating the existence of genetic factor(s) that affect their severity. In this study, we determined that another age-dependent phenotype, ectopic synapse formation, is also accelerated in the A/J retina compared to the B6 retina. Through genetic mapping utilizing recombinant inbred strains, we identified quantitative trait loci (QTLs) on chromosome 7 and 19, which contribute to abnormal retinal synapses as well as other age-dependent phenotypes. Using consomic single chromosome substitution lines where a single chromosome is from A/J and the rest of the genome is B6, we investigated the individual effect of each QTL on retinal aging phenotypes. We observed that both QTLs independently contribute to abnormal retinal synapses, reduction in the number of cone cells, and an up-regulation of retinal stress marker, glial fibrillary acidic protein (GFAP). Mice with a single chromosome substitution on chromosome 19 also exhibited an increase in inflammatory cells, which is characteristic of aging and age-related macular degeneration. Thus, we identified QTLs that are independently capable of affecting the severity and progression of age-dependent retinal abnormalities in mice.
C1 [Higuchi, Hitoshi; Macke, Erica L.; Lee, Wei-Hua; Miller, Sam A.; Xu, James C.; Ikeda, Sakae; Ikeda, Akihiro] Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA.
   [Ikeda, Sakae; Ikeda, Akihiro] Univ Wisconsin, McPherson Eye Res Inst, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison;
   University of Wisconsin System; University of Wisconsin Madison
RP Ikeda, A (通讯作者)，Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA.
EM emacke@wisc.edu; aikeda@wisc.edu
OI Macke, Erica/0000-0001-8324-506X; Ikeda, Akihiro/0000-0001-8440-3891
FU National Institutes of Health [NIH R21 EY023061, R01 EY022086]; Retina
   Research Foundation; Core Grant for Vision Research [P30 EY016665]; NIH
   predoctoral training program in Genetics [NIH T32 GM007133];  [NIH P30
   HD003352]; EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &
   HUMAN DEVELOPMENT [P30HD003352] Funding Source: NIH RePORTER; NATIONAL
   EYE INSTITUTE [R21EY023061, R01EY022086, P30EY016665] Funding Source:
   NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
   [T32GM007133] Funding Source: NIH RePORTER
FX The authors thank Satoshi Kinoshita for generation of frozen sections,
   Sharolyn Kawakami-Schulz for assistance with R/qtl, Joel Wipperfurth for
   assistance in genetic mapping, and the University of Wisconsin-Madison
   Genetics Confocal Facility for use of the confocal microscope. This work
   was supported by Grants from the National Institutes of Health (NIH R21
   EY023061 and R01 EY022086), a professorship from the Retina Research
   Foundation (Walter H. Helmerich Research Chair), Core Grant for Vision
   Research (P30 EY016665) and a core Grant to Waisman Center (NIH P30
   HD003352). Support for E.L.M. was partially provided by the NIH
   predoctoral training program in Genetics (NIH T32 GM007133).
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NR 34
TC 8
Z9 8
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-8990
EI 1432-1777
J9 MAMM GENOME
JI Mamm. Genome
PD FEB
PY 2015
VL 26
IS 1-2
BP 21
EP 32
DI 10.1007/s00335-014-9546-7
PG 12
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
GA AZ8CS
UT WOS:000348443100002
PM 25273269
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Sundermeier, TR
   Zhang, N
   Vinberg, F
   Mustafi, D
   Kohno, H
   Golczak, M
   Bai, XD
   Maeda, A
   Kefalov, VJ
   Palczewski, K
AF Sundermeier, Thomas R.
   Zhang, Ning
   Vinberg, Frans
   Mustafi, Debarshi
   Kohno, Hideo
   Golczak, Marcin
   Bai, Xiaodong
   Maeda, Akiko
   Kefalov, Vladimir J.
   Palczewski, Krzysztof
TI DICER1 is essential for survival of postmitotic rod photoreceptor cells
   in mice
SO FASEB JOURNAL
LA English
DT Article
DE microRNA; retina; conditional knockout; cell survival; age-related
   macular degeneration
ID MOUSE RETINA; MACULAR DEGENERATION; MICRORNAS; EYE; IDENTIFICATION;
   CLUSTER; PHOTOTRANSDUCTION; INACTIVATION; PHAGOCYTOSIS; RHODOPSIN
AB Photoreceptor cell death is the proximal cause of blindness in many retinal degenerative disorders; hence, understanding the gene regulatory networks that promote photoreceptor survival is at the forefront of efforts to combat blindness. Down-regulation of the microRNA (miRNA)-processing enzyme DICER1 in the retinal pigmented epithelium has been implicated in geographic atrophy, an advanced form of age-related macular degeneration (AMD). However, little is known about the function of DICER1 in mature rod photoreceptor cells, another retinal cell type that is severely affected in AMD. Using a conditional-knockout (cKO) mouse model, we report that loss of DICER1 in mature postmitotic rods leads to robust retinal degeneration accompanied by loss of visual function. At 14 wk of age, cKO mice exhibit a 90% reduction in photoreceptor nuclei and a 97% reduction in visual chromophore compared with those in control littermates. Before degeneration, cKO mice do not exhibit significant defects in either phototransduction or the visual cycle, suggesting that miRNAs play a primary role in rod photoreceptor survival. Using comparative small RNA sequencing analysis, we identified rod photoreceptor miRNAs of the miR-22, miR-26, miR-30, miR-92, miR-124, and let-7 families as potential factors involved in regulating the survival of rods.-Sundermeier, T. R., Zhang, N., Vinberg, F., Mustafi, D., Kohno, H., Golczak, M., Bai, X., Maeda, A., Kefalov, V. J., Palczewski, K. DICER1 is essential for survival of postmitotic rod photoreceptor cells in mice.
C1 [Sundermeier, Thomas R.; Zhang, Ning; Mustafi, Debarshi; Kohno, Hideo; Golczak, Marcin; Maeda, Akiko; Palczewski, Krzysztof] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA.
   [Bai, Xiaodong] Case Western Reserve Univ, Sch Med, Ctr RNA Mol Biol, Cleveland, OH 44106 USA.
   [Maeda, Akiko] Case Western Reserve Univ, Sch Med, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
   [Vinberg, Frans; Kefalov, Vladimir J.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
C3 Case Western Reserve University; Case Western Reserve University; Case
   Western Reserve University; Washington University (WUSTL)
RP Palczewski, K (通讯作者)，Case Western Reserve Univ, Dept Pharmacol, 10900 Euclid Ave, Cleveland, OH 44106 USA.
EM kxp65@case.edu
RI Vinberg, Frans/AAK-8615-2021
OI Vinberg, Frans/0000-0003-3439-4979; Mustafi,
   Debarshi/0000-0002-9164-7488; Kefalov, Vladimir/0000-0002-1659-008X
FU National Eye Institute, U.S. National Institutes of Health
   [R01EY0022326, R24EY021126, R01EY019312, EY002687, P30EY11373]; Research
   to Prevent Blindness; Foundation Fighting Blindness; NATIONAL EYE
   INSTITUTE [R24EY021126, P30EY011373, P30EY002687, R01EY019312,
   R01EY022326, F32EY022830] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007250] Funding Source: NIH
   RePORTER
FX The authors thank Dr. Neena Haider (Harvard Medical School, Cambridge,
   MA, USA) and Dr. Jason Chen (Virginia Commonwealth University, Richmond,
   VA, USA) for providing mice, Catherine Doller and Scott Howell of the
   Case Western Reserve University (CWRU) Visual Science Research Center
   Histology and Digital Imaging Cores for assistance with histological
   analysis, and Dr. Leslie T. Webster, Jr. (CWRU) for comments on the
   article. This work was supported by funding from the National Eye
   Institute, U.S. National Institutes of Health (grants R01EY0022326 to K.
   P., R24EY021126 to K. P. and V. J. K., R01EY019312 to V. J. K., EY002687
   to the Department of Ophthalmology and Visual Sciences at Washington
   University, and P30EY11373), Research to Prevent Blindness, and the
   Foundation Fighting Blindness. K. P. is the John H. Hord Professor of
   Pharmacology.
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NR 52
TC 45
Z9 45
U1 0
U2 0
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 AUG
PY 2014
VL 28
IS 8
BP 3780
EP 3791
DI 10.1096/fj.14-254292
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 AN0HM
UT WOS:000340265400043
PM 24812086
OA Green Published
DA 2022-11-30
ER

PT J
AU Schneider, EW
   Mruthyunjaya, P
   Talwar, N
   Nwanyanwu, KH
   Nan, B
   Stein, JD
AF Schneider, Eric W.
   Mruthyunjaya, Prithvi
   Talwar, Nidhi
   Nwanyanwu, Kristen Harris
   Nan, Bin
   Stein, Joshua D.
TI Reduced Fluorescein Angiography and Fundus Photography Use in the
   Management of Neovascular Macular Degeneration and Macular Edema During
   the Past Decade
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE utilization; age-related macular degeneration; macular edema; optical
   coherence tomography; fluorescein angiography
ID OPTICAL COHERENCE TOMOGRAPHY; CHOROIDAL NEOVASCULARIZATION; DOMAIN;
   PHOTOCOAGULATION; RANIBIZUMAB; GLAUCOMA; LEAKAGE; COSTS
AB PURPOSE. We assessed recent trends in the use of diagnostic testing for neovascular age-related macular degeneration (NVAMD) and macular edema (ME).
   METHODS. Claims data from a managed-care network were analyzed on patients with NVAMD (n = 22,954) or ME (n = 31,810) to assess the use of fluorescein angiography (FA), fundus photography (FP), and optical coherence tomography (OCT) from 2001 to 2009. Repeated-measures logistic regression was performed to compare patients' odds of undergoing these procedures in 2001, 2005, and 2009. In addition, the proportions of patients with an incident NVAMD or ME diagnosis in 2003 or 2008 who underwent FA, FP, and OCT were compared.
   RESULTS. From 2001 to 2009, among patients with NVAMD, the odds of undergoing OCT increased 23-fold, whereas the odds of receiving FA and FP decreased by 68% and 79%, respectively. Similar trends were observed for ME. From 2003 to 2008, the proportion of patients undergoing OCT within 1 year of initial diagnosis increased by 315% for NVAMD and by 143% for ME; the proportion undergoing OCT without FA within 1 year increased by 463% for NVAMD and by 216% for ME.
   CONCLUSIONS. Use of OCT increased dramatically during the past decade, whereas use of FA and FP declined considerably, suggesting that OCT may be replacing more traditional diagnostic testing in patients with NVAMD or ME. Future studies should evaluate whether this increased reliance on OCT instead of FA and FP affects patient outcomes.
C1 [Schneider, Eric W.; Mruthyunjaya, Prithvi] Duke Univ, Ctr Eye, Dept Ophthalmol, Durham, NC 27710 USA.
   [Schneider, Eric W.; Talwar, Nidhi; Nwanyanwu, Kristen Harris; Stein, Joshua D.] Univ Michigan, Dept Ophthalmol & Visual Sci, WK Kellogg Eye Ctr, Ann Arbor, MI 48105 USA.
   [Nan, Bin] Univ Michigan, Dept Biostat, Ann Arbor, MI 48105 USA.
C3 Duke University; 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, WK Kellogg Eye Ctr, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM jdstein@med.umich.edu
OI Stein, Joshua/0000-0003-2937-6987; mruthyunjaya,
   prithvi/0000-0003-1087-9736
FU National Eye Institute K23 Mentored Clinician Scientist Award
   [1K23EY019511-01]; Blue Cross Blue Shield of Michigan Foundation;
   Prevent Blindness Physician Scientist Award; NATIONAL EYE INSTITUTE
   [K23EY019511] Funding Source: NIH RePORTER
FX Supported by a National Eye Institute K23 Mentored Clinician Scientist
   Award (1K23EY019511-01; JDS), Blue Cross Blue Shield of Michigan
   Foundation (JDS), and a Research to Prevent Blindness Physician
   Scientist Award (JDS). The authors alone are responsible for the content
   and writing of the paper.
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   The American Medical Association, 2006, PHYS ICD 9 CM 2006
NR 28
TC 18
Z9 19
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 JAN
PY 2014
VL 55
IS 1
BP 542
EP 549
DI 10.1167/iovs.13-13034
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AB6DG
UT WOS:000331877200063
PM 24346174
OA Green Published
DA 2022-11-30
ER

PT J
AU Lu, B
   Zhu, DH
   Hinton, D
   Humayun, MS
   Tai, YC
AF Lu, Bo
   Zhu, Danhong
   Hinton, David
   Humayun, Mark S.
   Tai, Yu-Chong
TI Mesh-supported submicron parylene-C membranes for culturing retinal
   pigment epithelial cells
SO BIOMEDICAL MICRODEVICES
LA English
DT Article
DE Retina; Parylene-C; Permeability; Cell viability
ID BRUCHS MEMBRANE; SCAFFOLDS; GROWTH
AB In this work, a mesh-supported submicron parylene-C membrane (MSPM) is proposed as an artificial Bruch's membrane for the therapy of age-related macular degeneration (AMD). Any artificial Bruch's membrane must first satisfy two important requirements. First, it should be as permeable as healthy human Bruch's membrane to support nutrients transportation. Secondly, it should be able to support the adherence and proliferation of retinal pigment epithelial (RPE) cells with in vivo-like morphologies and functions. Although parylene-C is widely used as a barrier layer in many biomedical applications, it is found that parylene-C membranes with submicron thickness are semipermeable to macromolecules. We first measure the permeability of submicron parylene-C and find that 0.15-0.30 mu m parylene-C has similar permeability to healthy human Bruch's membranes. Blind-well perfusion cell viability experiments further demonstrate that nutrients and macromolecules can diffuse across 0.30 mu m parylene-C to nourish the cells. A mesh-supported submicron parylene-C membrane (MSPM) structure is design to enhance the mechanical strength of the substrate. In vitro cells culture on the MSPM (with 0.30 mu m ultrathin parylene-C) shows that H9-RPE cells are able to adhere, proliferate, form epithelial monolayer with tight intracellular junctions, and become well-polarized with microvilli, which exhibit similar characteristics to RPE cells in vivo. These studies have demonstrated the potential of the MSPM as an artificial Bruch's membrane for RPE cell transplantation.
C1 [Lu, Bo; Tai, Yu-Chong] CALTECH, Pasadena, CA 91125 USA.
   [Zhu, Danhong; Hinton, David; Humayun, Mark S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA.
   [Zhu, Danhong; Hinton, David; Humayun, Mark S.] Doheny Eye Inst, Los Angeles, CA 90033 USA.
C3 California Institute of Technology; University of Southern California;
   Doheny Eye Institute
RP Lu, B (通讯作者)，CALTECH, 1200 E Calif Blvd,MC 136-93, Pasadena, CA 91125 USA.
EM lubo@mems.caltech.edu
FU California Institute of Regenerative Medicine (CIRM); Disease Team
   Award;  [DR1-01444]
FX This work is supported by the California Institute of Regenerative
   Medicine (CIRM); Disease Team Award; Grant DR1-01444.
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NR 17
TC 88
Z9 97
U1 1
U2 23
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1387-2176
J9 BIOMED MICRODEVICES
JI Biomed. Microdevices
PD AUG
PY 2012
VL 14
IS 4
BP 659
EP 667
DI 10.1007/s10544-012-9645-8
PG 9
WC Engineering, Biomedical; Nanoscience & Nanotechnology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Science & Technology - Other Topics
GA 968BH
UT WOS:000305951500005
PM 22391881
DA 2022-11-30
ER

PT J
AU Zhang, H
   Liu, ZL
AF Zhang, Han
   Liu, Zhe-Li
TI Transforming growth factor -beta neutralizing antibodies inhibit
   subretinal fibrosis in a mouse model
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE transforming growth factor-beta; subretinal fibrosis; transforming
   growth factor-beta neutralizing antibody
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; CHOROIDAL
   NEOVASCULARIZATION; MESSENGER-RNA; EXPRESSION; RANIBIZUMAB; TGF-BETA-1;
   DISEASES; EYE; VITREORETINOPATHY
AB AIM: To determine the involvement of the transforming growth factor (TGF)-beta with the development of experimental subretinal fibrosis in a mouse model.
   METHODS: Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells (PECs) and the local expression of TGF-beta isoforms was assessed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at various time points. In addition, we investigated the effect of TFG-beta -neutralizing antibodies (TGF-beta NAb) on subretinal fibrosis development.
   RESULTS: TGF-beta 1 and TGF-beta 2 mRNA level was significantly elevated at day 2 after subretinal fibrosis induction and increased further to 5 and 6.5-fold respectively at day 5, reaching the peak. TGF-beta 3 mRNA was not detected in the present study. The result of ELSIA showed that active TGF-beta 1 and TGF-beta 2 levels were upregulated to 10-fold approximately, while total TGF-beta 1 and TGF-beta 2 levels were even upregulated more than 10-fold and more than 20-fold respectively in subretinal fibrosis mice in comparison with naive mice at day 5. TGF-beta NAb resulted in a reduced subretinal fibrosis areas by 65% compared to animals from control group at day 7.
   CONCLUSION: Our results indicate that TGF-beta signaling may contribute to the pathogenesis of subretinal fibrogenesis and TGF-beta inhibition may provide an effective, novel treatment of advanced and late-stage neovascular age-related macular degeneration.
C1 [Zhang, Han; Liu, Zhe-Li] China Med Univ, Hosp 1, Dept Ophthalmol, Shenyang 110001, Liaoning Provin, Peoples R China.
C3 China Medical University
RP Zhang, H (通讯作者)，China Med Univ, Hosp 1, Dept Ophthalmol, Shenyang 110001, Liaoning Provin, Peoples R China.
EM zhanghan0614@139.com
OI Zhang, Han/0000-0002-9338-0051
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NR 31
TC 22
Z9 23
U1 0
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 JUN 18
PY 2012
VL 5
IS 3
BP 307
EP 311
DI 10.3980/j.issn.2222-3959.2012.03.11
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 961XN
UT WOS:000305502900011
PM 22773978
DA 2022-11-30
ER

PT J
AU Brand, CS
AF Brand, C. S.
TI Management of retinal vascular diseases: a patient-centric approach
SO EYE
LA English
DT Review
DE age-related macular degeneration; diabetic retinopathy; retinal vein
   occlusion; anti-VEGF therapy; individualised medicine
ID ENDOTHELIAL GROWTH-FACTOR; OCCLUSION 12-MONTH OUTCOMES; MACULAR EDEMA
   SECONDARY; INTRAVITREAL TRIAMCINOLONE; DIABETIC-RETINOPATHY; SUSTAINED
   BENEFITS; STANDARD-CARE; RANIBIZUMAB; DEGENERATION; BRANCH
AB Retinal vascular diseases are a leading cause of blindness in the Western world. Advancement in the clinical management of these diseases has been fast-paced, with new treatments becoming available as well as license extensions of existing treatments. Vascular endothelial growth factor (VEGF) has been implicated in certain retinal vascular diseases, including wet age-related macular degeneration (AMD), diabetic macular oedema (DMO), and retinal vein occlusion (RVO). Treatment of wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO with an anti-VEGF on an as needed basis, rather than a fixed schedule, allows an individualised treatment approach; providing treatment when patients are most likely to benefit from it, while minimising the number of unnecessary intravitreal injections. Thus, an individualised treatment regimen reduces the chances of over-treatment and under-treatment, optimising both the risk/benefit profile of the treatment and the efficient use of NHS resource. Streamlining of treatment for patients with wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO, by using one treatment with similar posology across all three diseases, may help to minimise burden of clinic capacity and complexity and hence optimise patient outcomes. Informed treatment decisions and efficient clinic throughput are important for optimal patient outcomes in the fast-changing field of retinal vascular diseases. Eye (2012) 26, S1-S16; doi:10.1038/eye.2012.32
C1 Royal Hallamshire Hosp, Eye Dept, Sheffield S10 2JF, S Yorkshire, England.
C3 University of Sheffield
RP Brand, CS (通讯作者)，Royal Hallamshire Hosp, Eye Dept, Glossop Rd, Sheffield S10 2JF, S Yorkshire, England.
EM christopher.brand@sth.nhs.uk
FU Novartis Pharmaceuticals Limited (UK)
FX This study was supported by Novartis Pharmaceuticals Limited (UK).
   Novartis Pharmaceuticals Limited (UK) has had the opportunity to comment
   on the medical content and accuracy of the article; however, final
   editorial content resides with the author and the journal. We thank Sue
   Harris from ApotheCom, who provided medical writing support on behalf of
   Novartis Pharmaceuticals.
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NR 76
TC 49
Z9 50
U1 0
U2 8
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 APR
PY 2012
VL 26
SU 2
BP S1
EP S16
DI 10.1038/eye.2012.32
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 928UK
UT WOS:000303011400001
PM 22495396
OA Green Published
DA 2022-11-30
ER

PT J
AU McKay, GJ
   Silvestri, G
   Chakravarthy, U
   Dasari, S
   Fritsche, LG
   Weber, BH
   Keilhauer, CN
   Klein, ML
   Francis, PJ
   Klaver, CC
   Vingerling, JR
   Ho, L
   De Jong, PTDV
   Dean, M
   Sawitzke, J
   Baird, PN
   Guymer, RH
   Stambolian, D
   Orlin, A
   Seddon, JM
   Peter, I
   Wright, AF
   Hayward, C
   Lotery, AJ
   Ennis, S
   Gorin, MB
   Weeks, DE
   Kuo, CL
   Hingorani, AD
   Sofat, R
   Cipriani, V
   Swaroop, A
   Othman, M
   Kanda, A
   Chen, W
   Abecasis, GR
   Yates, JR
   Webster, AR
   Moore, AT
   Seland, JH
   Rahu, M
   Soubrane, G
   Tomazzoli, L
   Topouzis, F
   Vioque, J
   Young, IS
   Fletcher, AE
   Patterson, CC
AF McKay, Gareth J.
   Silvestri, Giuliana
   Chakravarthy, Usha
   Dasari, Shilpa
   Fritsche, Lars G.
   Weber, Bernhard H.
   Keilhauer, Claudia N.
   Klein, Michael L.
   Francis, Peter J.
   Klaver, Caroline C.
   Vingerling, Johannes R.
   Ho, Lintje
   De Jong, Paulus T. D. V.
   Dean, Michael
   Sawitzke, Julie
   Baird, Paul N.
   Guymer, Robyn H.
   Stambolian, Dwight
   Orlin, Anton
   Seddon, Johanna M.
   Peter, Inga
   Wright, Alan F.
   Hayward, Caroline
   Lotery, Andrew J.
   Ennis, Sarah
   Gorin, Michael B.
   Weeks, Daniel E.
   Kuo, Chia-Ling
   Hingorani, Aroon D.
   Sofat, Reecha
   Cipriani, Valentina
   Swaroop, Anand
   Othman, Mohammad
   Kanda, Atsuhiro
   Chen, Wei
   Abecasis, Goncalo R.
   Yates, John R.
   Webster, Andrew R.
   Moore, Anthony T.
   Seland, Johan H.
   Rahu, Mati
   Soubrane, Gisele
   Tomazzoli, Laura
   Topouzis, Fotis
   Vioque, Jesus
   Young, Ian S.
   Fletcher, Astrid E.
   Patterson, Chris C.
TI Variations in Apolipoprotein E Frequency With Age in a Pooled Analysis
   of a Large Group of Older People
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE aged; apolipoprotein E2; apolipoprotein E3; apolipoprotein E4;
   apolipoproteins E; longevity; meta-analysis; multicenter study
ID ONSET ALZHEIMERS-DISEASE; MACULAR DEGENERATION; RISK-FACTORS; E GENE; E
   POLYMORPHISM; APOE GENOTYPE; ASSOCIATION; LONGEVITY; GENDER; ALLELE
AB Variation in the apolipoprotein E gene (APOE) has been reported to be associated with longevity in humans. The authors assessed the allelic distribution of APOE isoforms epsilon 2, epsilon 3, and epsilon 4 among 10,623 participants from 15 case-control and cohort studies of age-related macular degeneration (AMD) in populations of European ancestry (study dates ranged from 1990 to 2009). The authors included only the 10,623 control subjects from these studies who were classified as having no evidence of AMD, since variation within the APOE gene has previously been associated with AMD. In an analysis stratified by study center, gender, and smoking status, there was a decreasing frequency of the APOE epsilon 4 isoform with increasing age (chi(2) for trend 14.9 (1 df); P = 0.0001), with a concomitant increase in the epsilon 3 isoform (chi(2) for trend 11.3 (1 df); P = 0.001). The association with age was strongest in epsilon 4 homozygotes; the frequency of epsilon 4 homozygosity decreased from 2.7% for participants aged 60 years or less to 0.8% for those over age 85 years, while the proportion of participants with the epsilon 3/epsilon 4 genotype decreased from 26.8% to 17.5% across the same age range. Gender had no significant effect on the isoform frequencies. This study provides strong support for an association of the APOE gene with human longevity.
C1 [McKay, Gareth J.; Young, Ian S.; Patterson, Chris C.] Queens Univ Belfast, Ctr Publ Hlth, Belfast BT12 6BA, Antrim, North Ireland.
   [Silvestri, Giuliana; Chakravarthy, Usha; Dasari, Shilpa] Queens Univ Belfast, Ctr Vision & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland.
   [Fritsche, Lars G.; Weber, Bernhard H.] Univ Regensburg, Inst Human Genet, Regensburg, Germany.
   [Keilhauer, Claudia N.] Univ Hosp Wurzburg, Dept Ophthalmol, Wurzburg, Germany.
   [Klein, Michael L.; Francis, Peter J.] Oregon Hlth & Sci Univ, Casey Eye Inst, Macular Degenerat Ctr, Portland, OR 97201 USA.
   [Vingerling, Johannes R.; Ho, Lintje] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
   [Klaver, Caroline C.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
   [De Jong, Paulus T. D. V.] Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Amsterdam, Netherlands.
   [De Jong, Paulus T. D. V.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands.
   [Dean, Michael; Sawitzke, Julie] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
   [Baird, Paul N.; Guymer, Robyn H.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Stambolian, Dwight; Orlin, Anton] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
   [Seddon, Johanna M.] Tufts Med Ctr, Boston, MA USA.
   [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
   [Wright, Alan F.; Hayward, Caroline] Western Gen Hosp, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Lotery, Andrew J.] Univ Southampton, Sch Med, Clin Neurosci Div, Southampton, Hants, England.
   [Lotery, Andrew J.] Southampton Gen Hosp, Southampton Eye Unit, Southampton SO9 4XY, Hants, England.
   [Ennis, Sarah] Univ Southampton, Div Human Genet, Genet Epidemiol & Bioinformat Grp, Southampton, Hants, England.
   [Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Weeks, Daniel E.; Kuo, Chia-Ling] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
   [Hingorani, Aroon D.; Sofat, Reecha] UCL, Dept Med, Univ Ctr Clin Pharmacol, London, England.
   [Swaroop, Anand; Othman, Mohammad] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
   [Swaroop, Anand; Kanda, Atsuhiro] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA.
   [Chen, Wei; Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
   [Yates, John R.] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge, England.
   [Cipriani, Valentina; Yates, John R.; Webster, Andrew R.; Moore, Anthony T.] UCL, Inst Ophthalmol, London, England.
   [Cipriani, Valentina; Yates, John R.; Webster, Andrew R.; Moore, Anthony T.] Moorfields Eye Hosp, London, England.
   [Seland, Johan H.] Univ Bergen, Stavanger Univ Hosp, Eye Dept, Stavanger, Norway.
   [Rahu, Mati] Natl Inst Hlth Dev, Dept Epidemiol & Biostat, Tallinn, Estonia.
   [Soubrane, Gisele] Univ Paris 12, Clin Ophthalmol, Paris, France.
   [Tomazzoli, Laura] Univ Verona, Clin Oculist, I-37100 Verona, Italy.
   [Topouzis, Fotis] Aristotle Univ Thessaloniki, Sch Med, Dept Ophthalmol, GR-54006 Thessaloniki, Greece.
   [Vioque, Jesus] Univ Miguel Hernandez, Dept Salud Publ, Alicante, Spain.
   [Vioque, Jesus] Consorcio Invest Biomed Red Especializado Epidemi, Alicante, Spain.
   [Fletcher, Astrid E.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
C3 Queens University Belfast; Queens University Belfast; University of
   Regensburg; University of Wurzburg; Oregon Health & Science University;
   Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam;
   Erasmus MC; Royal Netherlands Academy of Arts & Sciences; Netherlands
   Institute for Neuroscience (NIN-KNAW); University of Amsterdam; Academic
   Medical Center Amsterdam; National Institutes of Health (NIH) - USA; NIH
   National Cancer Institute (NCI); Centre for Eye Research Australia;
   Royal Victorian Eye & Ear Hospital; University of Melbourne; University
   of Pennsylvania; Tufts University; Tufts Medical Center; Icahn School of
   Medicine at Mount Sinai; University of Edinburgh; University of
   Southampton; University of Southampton; University of Southampton;
   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; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); University of
   Pittsburgh; University of London; University College London; University
   of Michigan System; University of Michigan; National Institutes of
   Health (NIH) - USA; NIH National Eye Institute (NEI); University of
   Michigan System; University of Michigan; University of Cambridge;
   University of London; University College London; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   Stavanger University Hospital; University of Bergen; National Institute
   for Health Development - Estonia; Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); University of Verona; Aristotle
   University of Thessaloniki; Universidad Miguel Hernandez de Elche;
   University of London; London School of Hygiene & Tropical Medicine
RP McKay, GJ (通讯作者)，Queens Univ Belfast, Royal Victoria Hosp, Ctr Publ Hlth, Belfast BT12 6BA, Antrim, North Ireland.
EM g.j.mckay@qub.ac.uk
RI Hayward, Caroline/M-8818-2016; Dean, Michael/R-7501-2019; Fritsche, Lars
   G/AAF-9387-2019; Cipriani, Valentina/A-8549-2012; Abecasis, Goncalo
   R/B-7840-2010; Dean, Michael C/G-8172-2012; McKay, Gareth/AAZ-2601-2020;
   Weeks, Daniel E/B-2995-2012; Vioque, Jesus/A-1066-2008; Klaver, Caroline
   C.W./A-2013-2016; Chen, Wei/AAX-5994-2020; Rahu, Mati/A-9981-2008
OI Hayward, Caroline/0000-0002-9405-9550; Fritsche, Lars
   G/0000-0002-2110-1690; Cipriani, Valentina/0000-0002-0839-9955; Dean,
   Michael C/0000-0003-2234-0631; McKay, Gareth/0000-0001-8197-6280; Weeks,
   Daniel E/0000-0001-9410-7228; Vioque, Jesus/0000-0002-2284-148X; Chen,
   Wei/0000-0001-7196-8703; Silvestri, Giuliana/0000-0001-5662-5374; Weber,
   Bernhard H.F./0000-0002-8808-7723; Lotery, Andrew/0000-0001-5541-4305;
   Young, Ian/0000-0003-3890-3152; Hingorani, Aroon/0000-0001-8365-0081;
   Abecasis, Goncalo/0000-0003-1509-1825; Sofat,
   Reecha/0000-0002-0242-6115; Chakravarthy, Usha/0000-0002-2606-3734;
   Baird, Paul/0000-0002-1305-3502; Klaver, Caroline/0000-0002-2355-5258;
   Swaroop, Anand/0000-0002-1975-1141; Guymer, Robyn/0000-0002-9441-4356;
   Sawitzke, Julie/0000-0002-1715-4626; Topouzis, Fotis/0000-0002-8966-537X
FU Guide Dogs for the Blind Association (Reading, United Kingdom) [2008-5a,
   OR2006-02d]; United Kingdom Medical Research Council [G0000067];
   Estonian Ministry of Science and Education [SF0940026s07]; Research and
   Development Office of Northern Ireland Health Personal Social Services
   [RRG 4.5]; European Union; Deutsche Forschungsgemeinschaft [WE1259/18-1,
   WE1259/19-1]; Alcon Research Institute; Ruth and Milton Steinbach
   Foundation; Tufts University School of Medicine; Macular Degeneration
   Research Fund-Tufts Medical Center; Massachusetts Lions Eye Research
   Fund; Research to Prevent Blindness USA; Foundation Fighting Blindness;
   United Kingdom Department of Health, National Institute for Health
   Research to Moorfields Eye Hospital NHS Foundation Trust; University
   College London Institute of Ophthalmology for a Specialist Biomedical
   Research Centre for Ophthalmology; JACOM Foundation; National Health and
   Medical Research Council (Canberra, Australia); MRC [G0601354]; ESRC
   [ES/G007438/1] Funding Source: UKRI; MRC [G0000067] Funding Source:
   UKRI; Economic and Social Research Council [ES/G007438/1] Funding
   Source: researchfish; Medical Research Council [G0601354, G0000067]
   Funding Source: researchfish; National Institute for Health Research
   [NF-SI-0507-10094] Funding Source: researchfish; NATIONAL CANCER
   INSTITUTE [ZIABC011301] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [ZIAEY000475, R01EY011309] Funding Source: NIH RePORTER
FX Funding was provided by the Guide Dogs for the Blind Association
   (Reading, United Kingdom) (grants 2008-5a [Giuliana Silvestri] and
   OR2006-02d [John R. Yates]); the United Kingdom Medical Research Council
   (grant G0000067 [John R. Yates]); the Estonian Ministry of Science and
   Education (grant SF0940026s07 [Mati Rahu]); the Research and Development
   Office of Northern Ireland Health Personal Social Services (grant RRG
   4.5 [Giuliana Silvestri]); EVI-GENORET, an integrated project funded
   through the European Union Research Project (grant FP6 [Usha
   Chakravarthy]); the Deutsche Forschungsgemeinschaft (grants WE1259/18-1
   and WE1259/19-1 [Bernhard H. Weber]); the Alcon Research Institute and
   the Ruth and Milton Steinbach Foundation (New York, New York) (Bernhard
   H. Weber); a Russo Grant from Tufts University School of Medicine
   (Johanna M. Seddon); the Macular Degeneration Research Fund-Tufts
   Medical Center (Johanna M. Seddon); the Massachusetts Lions Eye Research
   Fund (Johanna M. Seddon); Research to Prevent Blindness USA (Michael L.
   Klein, Peter J. Francis); the Foundation Fighting Blindness (Peter J.
   Francis); financial support from the United Kingdom Department of Health
   through an award made by the National Institute for Health Research to
   Moorfields Eye Hospital NHS Foundation Trust and University College
   London Institute of Ophthalmology for a Specialist Biomedical Research
   Centre for Ophthalmology (John R. Yates); the JACOM Foundation (Paul N.
   Baird); and a National Health and Medical Research Council (Canberra,
   Australia) Practitioner Award (Robyn H. Guymer). The Centre for Eye
   Research Australia receives operational infrastructure support from the
   Victorian government (Paul N. Baird, Robyn H. Guymer), the Macular
   Disease Society (Gareth J. McKay, Andrew J. Lotery), the T.F.C. Frost
   Charity (Andrew J. Lotery), and the British Council for the Prevention
   of Blindness (Andrew J. Lotery). Genetic analysis in the European Eye
   Study was supported by an MRC Biomarker Award (grant G0601354 [Aroon D.
   Hingorani, Astrid E. Fletcher]).
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NR 38
TC 62
Z9 65
U1 0
U2 17
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 15
PY 2011
VL 173
IS 12
BP 1357
EP 1364
DI 10.1093/aje/kwr015
PG 8
WC Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Public, Environmental & Occupational Health
GA 775UK
UT WOS:000291488700002
PM 21498624
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Peng, SM
   Rao, VS
   Adelman, RA
   Rizzolo, LJ
AF Peng, Shaomin
   Rao, Veena S.
   Adelman, Ron A.
   Rizzolo, Lawrence J.
TI Claudin-19 and the Barrier Properties of the Human Retinal Pigment
   Epithelium
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID TIGHT JUNCTION PERMEABILITY; PARACELLULAR PORES; ION PERMEATION; RPE
   CELLS; PROTEIN; OCCLUDIN; SELECTIVITY; EXPRESSION; PHOSPHORYLATION;
   ALDOSTERONE
AB PURPOSE. The retinal pigment epithelium (RPE) separates photoreceptors from choroidal capillaries, but in age-related macular degeneration (AMD) capillaries breach the RPE barrier. Little is known about human RPE tight junctions or the effects of serum on the retinal side of the RPE.
   METHODS. Cultured human fetal RPE (hfRPE) was assessed by the transepithelial electrical resistance (TER) and the transepithelial diffusion of methylated polyethylene glycol (mPEG). Claudins and occludin were monitored by quantitative RT-PCR, immunoblotting, and immunofluorescence.
   RESULTS. Similar to freshly isolated hfRPE, claudin-19 mRNA was 25 times more abundant than claudin-3. Other detectable claudin mRNAs were found in even lesser amounts, as little as 3000 times less abundant than claudin-19. Claudin-1 and claudin-10b were detected only in subpopulations of cells, whereas others were undetectable. Knockdown of claudin-19 by small interfering RNA (siRNA) eliminated the TER. siRNAs for other claudins had minimal effects. Serum affected tight junctions only when presented to the retinal side of the RPE. The TER increased 2 times, and the conductance of K+ relative to Na+ decreased without affecting the permeability of mPEG. These effects correlated with increased steady-state levels of occludin.
   CONCLUSIONS. Fetal human RPE is a claudin-19-dominant epithelium that has regional variations in claudin-expression. Apical serum decreases RPE permeability, which might be a defense mechanism that would retard the spread of edema due to AMD. (Invest Ophthalmol Vis Set. 2011;52:1392-1403) DOI: 10.1167/iovs.10-5984
C1 [Peng, Shaomin; Rizzolo, Lawrence J.] Yale Univ, Dept Surg, Sch Med, New Haven, CT 06520 USA.
   [Peng, Shaomin; Rao, Veena S.; Adelman, Ron A.; Rizzolo, Lawrence J.] Yale Univ, Dept Ophthalmol, Sch Med, New Haven, CT 06520 USA.
   [Peng, Shaomin] Harbin Univ, Dept Ophthalmol, Affiliated Hosp 2, Harbin, Peoples R China.
C3 Yale University; Yale University; Harbin University
RP Rizzolo, LJ (通讯作者)，Yale Univ, Dept Surg, Sch Med, POB 208062, New Haven, CT 06520 USA.
EM lawrence.rizzolo@yale.edu
OI Rizzolo, Lawrence/0000-0002-2393-8419; Rao, Veena/0000-0002-7602-6309
FU National Eye Institute, Yale University [EY000785]; international
   Retinal Research Foundation; Leir Foundation; Newman's Own Foundation;
   National Natural Science Foundation of China [30772381]; Yale Endowed
   Student's Research Fellowship; NATIONAL EYE INSTITUTE [P30EY000785]
   Funding Source: NIH RePORTER
FX Supported in part by the National Eye Institute vision core grant
   EY000785 (Yale University), the international Retinal Research
   Foundation (LJR), Leir Foundation (RA), Newman's Own Foundation (RAA),
   National Natural Science Foundation of China Grant No. 30772381 (SP),
   and the Yale Endowed Student's Research Fellowship (VSR).
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NR 53
TC 57
Z9 60
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 MAR
PY 2011
VL 52
IS 3
BP 1392
EP 1403
DI 10.1167/iovs.10-5984
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 742SR
UT WOS:000288965300025
PM 21071746
OA Green Published
DA 2022-11-30
ER

PT J
AU Wasmuth, S
   Lueck, K
   Baehler, H
   Lommatzsch, A
   Pauleikhoff, D
AF Wasmuth, Susanne
   Lueck, Katharina
   Baehler, Hanna
   Lommatzsch, Albrecht
   Pauleikhoff, Daniel
TI Increased Vitronectin Production by Complement-Stimulated Human Retinal
   Pigment Epithelial Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; DRUSEN FORMATION;
   GENE-EXPRESSION; MESSENGER-RNA; FACTOR-B; VARIANT; RISK;
   ATHEROSCLEROSIS; ACTIVATION
AB PURPOSE. A variation in the complement factor H gene was associated with an enhanced risk to develop especially early age-related macular degeneration. Drusen and basal laminar deposits are hallmarks of this AMD manifestation that contain vitronectin as a major component. In this study, the correlation between complement stimulation and vitronectin production of retinal pigment epithelial (RPE) cells was investigated.
   METHODS. ARPE-19 cells, a permanent cell line of human RPE cells, were supplemented with and without human complement competent serum in medium with and without heat inactivated fetal calf serum. The cells were examined in situ for their vitronectin production as an effective inhibitor of alternatively activated complement by immunohistochemistry. Semi-quantitative RT-PCR and Western blots were performed to analyze vitronectin mRNA and protein.
   RESULTS. A strong immunohistochemical staining for vitronectin was observed after complement supplementation. The enhanced production of this complement inactivator by ARPE-19 cells was confirmed by Western blot, whereas the expression analysis revealed unaltered mRNA amounts.
   CONCLUSIONS. A stimulation of RPE cells with complement resulted in an upregulated production of vitronectin. This may support the concept of a protective mechanism, since vitronectin is the major inhibitor of complement activated by the alternative pathway. On the other hand, this increased vitronectin production after complement stimulation may contribute to focal or diffuse deposits in Bruch's membrane, as observed in early AMD. (Invest Ophthalmol Vis Sci. 2009;50:5304-5309) DOI:10.1167/iovs.08-3326
C1 [Wasmuth, Susanne; Lueck, Katharina; Baehler, Hanna; Lommatzsch, Albrecht; Pauleikhoff, Daniel] St Franziskus Hosp, Dept Ophthalmol, Ophtha Lab, Munster, Germany.
   [Pauleikhoff, Daniel] Univ Duisburg Essen, Dept Ophthalmol, Essen, Germany.
C3 St. Franziskus-Hospital; University of Duisburg Essen
RP Pauleikhoff, D (通讯作者)，Augenarzte St Franziskus Hosp, Hohenzollernring 74, D-48145 Munster, Germany.
EM dapauleikhoff@muenster.de
FU Voltmann Foundation; Akademie des Sehens
FX Supported by Voltmann Foundation and Akademie des Sehens.
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NR 38
TC 22
Z9 22
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 NOV
PY 2009
VL 50
IS 11
BP 5304
EP 5309
DI 10.1167/iovs.08-3326
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 514XH
UT WOS:000271429200039
PM 19407013
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Lepri, BP
AF Lepri, Bernard P.
TI Is acuity enough? Other considerations in clinical investigations of
   visual prostheses
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
CT Eye and the Chip Meeting 2008
CY JUN 12-14, 2008
CL Detroit, MI
SP Detroit Inst Ophthalmol
AB Visual impairing eye diseases are the major frontier facing ophthalmic research today in light of our rapidly aging population. The visual skills necessary for improving the quality of daily function and life are inextricably linked to these impairing diseases. Both research and reimbursement programs are emphasizing outcome-based results. Is improvement in Visual acuity alone enough to improve the function and quality of life Of Visually impaired persons? This perspective summarizes the types of effectiveness endpoints for clinical investigations of visual prostheses that go beyond visual acuity. The clinical investigation of visual prostheses should include visual function, functional vision and quality Of life measures. Specifically, they encompass contrast sensitivity, orientation and mobility, activities of daily living and quality of life assessments. The perspective focuses on the design of clinical trials for visual prostheses and the methods of determining effectiveness above and beyond Visual acuity that will yield outcomes that are measured by improved function in the Visual world and quality of life. The visually impaired population is the primary con side rat ion in this presentation with particular emphases on retinitis pigmentosa and age-related macular degeneration. Clinical trials for visual prostheses cannot be isolated from the need for medical rehabilitation in order to obtain measurements of effectiveness that produce outcomes/evidence-based Success. This approach will facilitate improvement in daily function and quality of life of patients with diseases that cause chronic vision impairment.
C1 US FDA, Rockville, MD 20852 USA.
C3 US Food & Drug Administration (FDA)
RP Lepri, BP (通讯作者)，US FDA, Rockville, MD 20852 USA.
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NR 7
TC 14
Z9 14
U1 0
U2 2
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 1741-2560
J9 J NEURAL ENG
JI J. Neural Eng.
PD JUN
PY 2009
VL 6
IS 3
AR 035003
DI 10.1088/1741-2560/6/3/035003
PG 4
WC Engineering, Biomedical; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Neurosciences & Neurology
GA 461AM
UT WOS:000267235600004
PM 19458402
DA 2022-11-30
ER

PT J
AU Hassenstein, A
   Meyer, CH
AF Hassenstein, Andrea
   Meyer, Carsten H.
TI Clinical use and research applications of Heidelberg retinal angiography
   and spectral-domain optical coherence tomography - a review
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Review
DE fluorescein angiography; fundus autofluorescence; Heidelberg retina
   angiography; indocyanine green angiography; optical coherence tomography
ID SCANNING LASER OPHTHALMOSCOPE; INDOCYANINE GREEN ANGIOGRAPHY;
   INTEGRATION METHOD DIM; MACULAR DEGENERATION; FUNDUS AUTOFLUORESCENCE;
   GEOGRAPHIC ATROPHY; FLUORESCEIN ANGIOGRAPHY; OCT; TELANGIECTASIA;
   RETINOPATHY
AB Fluorescein angiography (FA) was discovered by Nowotny and Alvis in the 1960s of the 20th century and has evolved to become the 'Gold standard' for macular diagnostics. Scanning laser imaging technology achieved enhancement of contrast and resolution. The combined Heidelberg retina angiograph (HRA2) adds novel innovative features to established fundus cameras. The principle of confocal scanning laser imaging provides a high resolution of retinal and choroidal vasculature with low light exposure providing comfort and safety for the patient. Enhanced contrast, details and image sharpness image are generated using confocality. For the visualization of the choroid an indocyanine green angiography (ICGA) is the most suitable application. The main indications for ICGA are age-related macular degeneration, choroidal polypoidal vasculopathy and choroidal haemangiomas. Simultaneous digital FA and ICGA images with three-dimensional resolution offer improved diagnosis of retinal and choroidal pathologies. High-speed ICGA dynamic imaging can identify feeder vessels and retinal choroidal anastomoses, ensuring safer treatment of choroidal neovascularization. Autofluorescence imaging and fundus reflectance imaging with blue and infrared light offer new follow-up parameters for retinal diseases. Finally, the real-time optical coherence tomography provides a new level of accuracy for assessment of the angiographic and morphological correlation. The combination of various macular diagnostic tools, such as infrared, blue reflectance, fundus autofluorescence, FA, ICGA and also spectral domain optical coherence tomography, lead to a better understanding and improved knowledge of macular diseases.
C1 [Hassenstein, Andrea] Univ Eye Hosp, Hamburg, Germany.
   [Meyer, Carsten H.] Univ Bonn, Dept Ophthalmol, D-5300 Bonn, Germany.
C3 University of Bonn
RP Hassenstein, A (通讯作者)，Univ Eye Hosp Hamburg Eppendorf, Martinistr 52, D-20251 Hamburg, Germany.
EM hassenstein@uke.uni-hamburg.de
RI Meyer, Carsten/A-3981-2017
OI Meyer, Carsten/0000-0002-0530-5298
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NR 45
TC 96
Z9 103
U1 3
U2 19
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1442-6404
EI 1442-9071
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD JAN-FEB
PY 2009
VL 37
IS 1
BP 130
EP 143
DI 10.1111/j.1442-9071.2009.02017.x
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 425AO
UT WOS:000264609600011
PM 19338610
OA Bronze
DA 2022-11-30
ER

PT J
AU Hu, JY
   Zhu, ML
   Li, D
   Wu, Q
   Le, YZ
AF Hu, Jianyan
   Zhu, Meili
   Li, Dai
   Wu, Qiang
   Le, Yun-Zheng
TI VEGF as a Direct Functional Regulator of Photoreceptors and Contributing
   Factor to Diabetes-Induced Alteration of Photoreceptor Function
SO BIOMOLECULES
LA English
DT Article
DE VEGF; photoreceptors; neuronal function; ERG; diabetic retinopathy
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL NEURONS; ROD PHOTORECEPTORS; CRE
   RECOMBINASE; SURVIVAL FACTOR; MULLER GLIA; RETINOPATHY; EXPRESSION;
   TRANSMISSION; MOUSE
AB Vascular endothelial growth factor (VEGF) is a major therapeutic target for blood-retina barrier (BRB) breakdown in diabetic retinopathy (DR), age-related macular degeneration (AMD), and other hypoxic retinal vascular disorders. To determine whether VEGF is a direct regulator of retinal neuronal function and its potential role in altering vision during the progression of DR, we examined the immediate impact of recombinant VEGF (rVEGF) on photoreceptor function with electroretinography in C57BL6 background wild-type (WT) and Akita spontaneous diabetic mice. Shortly after intravitreal injections, rVEGF caused a significant reduction of scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes in a dose-dependent manner in dark-adapted 1.5-mo-old WT mice. Compared with WT controls, 5-mo-old Akita spontaneous diabetic mice demonstrated a significant reduction in scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes. However, the effect of rVEGF altered photoreceptor function in WT controls was diminished in 5-mo-old Akita spontaneous diabetic mice. In conclusion, our results suggest that VEGF is a direct functional regulator of photoreceptors and VEGF up-regulation in DR is a contributing factor to diabetes-induced alteration of photoreceptor function. This information is critical to the understanding of the therapeutic effect and to the care of anti-VEGF drug-treated patients for BRB breakdown in DR, AMD, and other hypoxic retinal vascular disorders.
C1 [Hu, Jianyan; Zhu, Meili; Li, Dai; Le, Yun-Zheng] Univ Oklahoma, Dept Med, Sect Endocrinol Diabet & Metab, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
   [Hu, Jianyan; Wu, Qiang] Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Dept Ophthalmol, Shanghai 200233, Peoples R China.
   [Li, Dai] Hubei Univ Sci & Technol, Sch Optometry, Xianning 437100, Peoples R China.
   [Wu, Qiang] Shanghai Key Lab Diabet Mellitus, Shanghai 200233, Peoples R China.
   [Le, Yun-Zheng] Univ Oklahoma, Dept Cell Biol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
   [Le, Yun-Zheng] Univ Oklahoma, Dept Ophthalmol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
   [Le, Yun-Zheng] Univ Oklahoma, Harold Hamm Diabet Ctr, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; Shanghai Jiao Tong University; Hubei University of Science &
   Technology; 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
RP Le, YZ (通讯作者)，Univ Oklahoma, Dept Med, Sect Endocrinol Diabet & Metab, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.; Wu, Q (通讯作者)，Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Dept Ophthalmol, Shanghai 200233, Peoples R China.; Wu, Q (通讯作者)，Shanghai Key Lab Diabet Mellitus, Shanghai 200233, Peoples R China.; Le, YZ (通讯作者)，Univ Oklahoma, Dept Cell Biol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.; Le, YZ (通讯作者)，Univ Oklahoma, Dept Ophthalmol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.; Le, YZ (通讯作者)，Univ Oklahoma, Harold Hamm Diabet Ctr, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
EM jianyanhu79@126.com; Meili-Zhu@ouhsc.edu; lidai008@21cn.com;
   qiang.wu@shsmu.edu.cn; Yun-Le@ouhsc.edu
FU NIH [R01EY26970, R01EY20900, P30EY021725, P30GM122744]; Research to
   Prevent Blindness, Oklahoma Center for the Advancement of Science and
   Technology [HR20-065]; Oklahoma Center for Adult Stem Cell Research (a
   program of TSET); Presbyterian Health Foundation; National Natural
   Science Foundation of China [81070738, 81300775]; endowed Chair Funds
   from Choctaw Nation and Mr. Harold Hamm
FX This research was supported by NIH grants R01EY26970, R01EY20900,
   P30EY021725, P30GM122744, grants from Research to Prevent Blindness,
   Oklahoma Center for the Advancement of Science and Technology
   (HR20-065), Oklahoma Center for Adult Stem Cell Research (a program of
   TSET), Presbyterian Health Foundation, grants 81070738 and 81300775 from
   National Natural Science Foundation of China, and endowed Chair Funds
   from Choctaw Nation and Mr. Harold Hamm.
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NR 35
TC 2
Z9 2
U1 2
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2218-273X
J9 BIOMOLECULES
JI Biomolecules
PD JUL
PY 2021
VL 11
IS 7
AR 988
DI 10.3390/biom11070988
PG 10
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA TN7PX
UT WOS:000676423600001
PM 34356612
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Gorusupudi, A
   Rallabandi, R
   Li, BX
   Arunkumar, R
   Blount, JD
   Rognon, GT
   Chang, FY
   Wade, A
   Lucas, S
   Conboy, JC
   Rainier, JD
   Bernstein, PS
AF Gorusupudi, Aruna
   Rallabandi, Rameshu
   Li, Binxing
   Arunkumar, Ranganathan
   Blount, J. David
   Rognon, Gregory T.
   Chang, Fu-Yen
   Wade, Alexander
   Lucas, Steven
   Conboy, John C.
   Rainier, Jon D.
   Bernstein, Paul S.
TI Retinal bioavailability and functional effects of a synthetic
   very-long-chain polyunsaturated fatty acid in mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE retina; lipid; VLC-PUFA; ELOVL4; bioavailability
ID VLC-PUFA; ELOVL4; QUANTIFICATION; BIOSYNTHESIS; MUTATION; PROTEIN;
   VISION; ADULT
AB Rare, nondietary very-long-chain polyunsaturated fatty acids (VLC-PUFAs) are uniquely found in the retina and a few other vertebrate tissues. These special fatty acids play a clinically significant role in retinal degeneration and development, but their physiological and interventional research has been hampered because pure VLC-PUFAs are scarce. We hypothesize that if Stargardt-3 or age-related macular degeneration patients were to consume an adequate amount of VLC-PUFAs that could be directly used in the retina, it may be possible to bypass the steps of lipid elongation mediated by the retina's ELOVL4 enzyme and to delay or prevent degeneration. We report the synthesis of a VLC-PUFA (32:6 n-3) in sufficient quantity to study its bioavailability and functional benefits in the mouse retina. We acutely and chronically gavage fed wild-type mice and Elovl4 rodcone conditional knockout mice this synthetic VLC-PUFA to understand its bioavailability and its role in visual function. VLC-PUFA-fed wild-type and Elovl4 conditional knockout mice show a significant increase in retinal VLC-PUFA levels in comparison to controls. The VLC-PUFA-fed mice also had improvement in the animals' visual acuity and electroretinography measurements. Further studies with synthetic VLC-PUFAs will continue to expand our understanding of the physiological roles of these unique retinal lipids, particularly with respect to their potential utility for the treatment and prevention of retinal degenerative diseases.
C1 [Gorusupudi, Aruna; Li, Binxing; Arunkumar, Ranganathan; Blount, J. David; Rognon, Gregory T.; Chang, Fu-Yen; Bernstein, Paul S.] John Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA.
   [Rallabandi, Rameshu; Wade, Alexander; Lucas, Steven; Conboy, John C.; Rainier, Jon D.] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA.
C3 Utah System of Higher Education; University of Utah
RP Bernstein, PS (通讯作者)，John Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA.
EM paul.bernstein@hsc.utah.edu
RI Rallabandi, Rameshu/AAU-7028-2021; Chang, Fu-Yen/AAY-4891-2021; Blount,
   David/HCH-8713-2022
OI Rallabandi, Rameshu/0000-0003-4374-6120; Chang,
   Fu-Yen/0000-0003-0921-9773; BLOUNT, JUDSON/0000-0003-3208-2947; Li,
   Binxing/0000-0002-0715-7495
FU Knights Templar Career starter grant; University of Utah Center on Aging
   Seed grant; Foundation Fighting Blindness Grant [TA-NMT-0618-0736-UUT];
   Carl Marshall Reeves and Mildred Almen Reeves Foundation; Research to
   Prevent Blindness; NIH [EY14800]
FX This work was supported by a Knights Templar Career starter grant
   (A.G.), a University of Utah Center on Aging Seed grant (J.D.R.),
   Foundation Fighting Blindness Grant TA-NMT-0618-0736-UUT (P.S.B.), a
   Carl Marshall Reeves and Mildred Almen Reeves Foundation grant (P.S.B.),
   and departmental core grants from Research to Prevent Blindness and NIH
   (Grant EY14800). We thank Aniket Ramsekhar and Dr. Haibo Wang for their
   help with histology.
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Z9 6
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
EI 1091-6490
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 9
PY 2021
VL 118
IS 6
AR e2017739118
DI 10.1073/pnas.2017739118
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA QG1MR
UT WOS:000617355300051
PM 33526677
OA Green Published
DA 2022-11-30
ER

PT J
AU Zhu, ST
   Wang, H
   Zhang, ZH
   Ma, MM
   Zheng, Z
   Xu, X
   Sun, T
AF Zhu, Shuting
   Wang, Hong
   Zhang, Zhihua
   Ma, Mingming
   Zheng, Zhi
   Xu, Xun
   Sun, Tao
TI IGFBP-rP1-silencing promotes hypoxia-induced angiogenic potential of
   choroidal endothelial cells via the RAF/MEK/ERK signaling pathway
SO MOLECULAR MEDICINE REPORTS
LA English
DT Article
DE insulin-like growth factor binding protein-related protein 1; RAF; MEK;
   ERK signaling pathway; vascular endothelial growth factor; choroidal
   endothelial cells; hypoxia; angiogenesis
ID PROTEIN-RELATED PROTEIN-1; GROWTH-FACTOR; TUBE FORMATION; MACULAR
   DEGENERATION; RNA INTERFERENCE; VEGF; NEOVASCULARIZATION; PROLIFERATION;
   EXPRESSION; IGFBP7
AB Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) has been reported to have various functions in different cellular contexts. Our previous investigation discovered that IGFBP-rP1 inhibited retinal angiogenesis in vitro and in vivo by inhibiting the pro-angiogenic effect of VEGF and downregulating VEGF expression. Recently, IGFBP-rP1 was confirmed to be downregulated in the aqueous humor of patients with neovascular age-related macular degeneration compared with controls; however, its specific role remains unknown. The present study applied the technique of gene silencing, reverse transcription-quantitative PCR, western blotting, cell viability assays, cell motility assays and tube formation assays. Chemical hypoxic conditions and choroidal endothelial (RF/6A) cells were used to explore the effect of IGFBP-rP1-silencing on the phenotype activation of RF/6A cells under hypoxic conditions and to elucidate the underlying mechanisms. siRNA achieved IGFBP-rP1-silencing in RF/6A cells without cytotoxicity. IGFBP-rP1-silencing significantly restored the viability of RF/6A cells in hypoxia and enhanced hypoxia-induced migration and capillary-like tube formation of RF/6A cells. Furthermore, IGFBP-rP1-silencing significantly upregulated the expression of B-RAF, phosphorylated (p)-MEK, p-ERK and VEGF in RF/6A cells under hypoxic conditions; however, these upregulations were inhibited by exogenous IGFBP-rP1. These data indicated that silencing IGFBP-rP1 expression in RF/6A cells effectively promoted the hypoxia-induced angiogenic potential of choroidal endothelial cells by upregulating RAF/MEK/ERK signaling pathway activation and VEGF expression.
C1 [Zhu, Shuting; Wang, Hong; Zhang, Zhihua; Ma, Mingming; Zheng, Zhi; Xu, Xun; Sun, Tao] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Ophthalmol, 100 Haining Rd, Shanghai 200080, Peoples R China.
   [Zhu, Shuting; Wang, Hong; Zhang, Zhihua; Ma, Mingming; Zheng, Zhi; Xu, Xun; Sun, Tao] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Shanghai Key Lab Ocular Fundus Dis, Shanghai 200080, Peoples R China.
   [Wang, Hong; Zhang, Zhihua; Ma, Mingming; Zheng, Zhi; Xu, Xun; Sun, Tao] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Natl Clin Res Ctr Eye Dis, Sch Med, Shanghai 200080, Peoples R China.
   [Wang, Hong; Zhang, Zhihua; Ma, Mingming; Zheng, Zhi; Xu, Xun; Sun, Tao] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Shanghai Engn Ctr Visual Sci & Photomed, Sch Med, Shanghai 200080, Peoples R China.
   [Wang, Hong; Zhang, Zhihua; Ma, Mingming; Zheng, Zhi; Xu, Xun; Sun, Tao] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Shanghai Engn Ctr Precise Diag & Treatment Eye Di, Sch Med, Shanghai 200080, Peoples R China.
C3 Shanghai Jiao Tong University; Shanghai Jiao Tong University; Shanghai
   Jiao Tong University; Shanghai Jiao Tong University; Shanghai Jiao Tong
   University
RP Sun, T (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Ophthalmol, 100 Haining Rd, Shanghai 200080, Peoples R China.
EM drsuntao@yeah.net
RI zhang, zh/GWV-4677-2022
FU National Nature Science Foundation for Young Scholars of China
   [81200701]; National Key R&D Program of China [2016YFC0904800,
   2019YFC0840607]; National Science and Technology Major Project of China
   [2017ZX09304010]; Bethune Lumitin Research Funding for Young or
   Middle-aged Ophthalmologists [BJ-LM2019001J]
FX The present study was supported by grants from the National Nature
   Science Foundation for Young Scholars of China (grant no. 81200701), the
   National Key R&D Program of China (grant nos. 2016YFC0904800 and
   2019YFC0840607), the National Science and Technology Major Project of
   China (grant no. 2017ZX09304010) and the Bethune Lumitin Research
   Funding for Young or Middle-aged Ophthalmologists (grant no.
   BJ-LM2019001J).
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NR 76
TC 0
Z9 1
U1 0
U2 1
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 DEC
PY 2020
VL 22
IS 6
BP 4837
EP 4847
DI 10.3892/mmr.2020.11578
PG 11
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA OY0VS
UT WOS:000593973200040
PM 33173998
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Khan, M
   Aziz, AA
   Shafi, NA
   Abbas, T
   Khanani, AM
AF Khan, Majid
   Aziz, Aamir A.
   Shafi, Noah A.
   Abbas, Tayeb
   Khanani, Arshad M.
TI Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review
   and Summary of Clinical Trials Involving Faricimab
SO CELLS
LA English
DT Review
DE VEGF-A; Ang-2 and Ang-1 pathway; Tie-2 receptor; diabetic eye disease;
   VE-PTP; vascularization; VEGF; diabetic macular edema; retinal vascular
   disease; neovascular age-related macular degeneration
ID TIE2; ANGIOGENESIS; EXPRESSION; MIGRATION
AB This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies.
C1 [Khan, Majid; Shafi, Noah A.; Abbas, Tayeb; Khanani, Arshad M.] Univ Nevada, Reno Sch Med, Reno, NV 89557 USA.
   [Aziz, Aamir A.; Khanani, Arshad M.] Sierra Eye Associates, Reno, NV 89502 USA.
C3 Nevada System of Higher Education (NSHE); University of Nevada Reno
RP Khanani, AM (通讯作者)，Univ Nevada, Reno Sch Med, Reno, NV 89557 USA.; Khanani, AM (通讯作者)，Sierra Eye Associates, Reno, NV 89502 USA.
EM majidk@med.unr.edu; aamir.aziz@nevada.unr.edu; nshafi@med.unr.edu;
   tabbas@med.unr.edu; arshad.khanani@gmail.com
OI Khan, Majid/0000-0003-3569-7963
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NR 68
TC 19
Z9 19
U1 2
U2 6
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD AUG
PY 2020
VL 9
IS 8
AR 1869
DI 10.3390/cells9081869
PG 14
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA NI8VB
UT WOS:000565623800001
PM 32785136
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Rashid, K
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AF Rashid, Khalid
   Verhoyen, Mathilde
   Taiwo, Moyinoluwa
   Langmann, Thomas
TI Translocator protein (18 kDa) (TSPO) ligands activate Nrf2 signaling and
   attenuate inflammatory responses and oxidative stress in human retinal
   pigment epithelial cells
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Atrophic AMD; Retinal pigment epithelium; Microglia; LLOMe; TSPO
   ligands; NrF2 pathway
ID LYSOSOMAL DESTABILIZATION; MOUSE MODEL; RPE; DEGENERATION; OXYGENASE-1;
   MICROGLIA; TARGET; HEME
AB Degeneration of the retinal pigment epithelium (RPE) is a hallmark of atrophic age-related macular degeneration (AMD). Microglia mediated inflammatory responses and oxidative stress are critical pathophysiological processes in the onset and progression of RPE degeneration. Given the central role of the RPE, strategies to protect these cells from damage caused by oxidative stress and inflammation present a promising therapeutic approach to mitigate AMD. Ligands for the translocator protein (18 kDa) (TSPO) have been shown to confer protection against retinal inflammatory responses and neurodegeneration by acting primarily through retinal glia. However, despite RPE cells demonstrating strong TSPO expression, it remains unclear whether TSPO ligands could also inhibit inflammatory responses of RPE cells. Here, we investigated the influence of three different TSPO ligands XBD173, PK11195 and Ro5-4864 on inflammatory responses in human ARPE-19 cells triggered by supernatants from reactive human microglial cells and the lysosomal destabilizer, LLOMe. Our findings revealed that TSPO ligands significantly inhibited proinflammatory gene expression, inflammasome-mediated caspase-1 activation, lipid accumulation and intracellular ROS levels in stressed ARPE-19 cells. Notably, TSPO ligands induced activation of Nrf2 pathway and its downstream regulated genes in ARPE-19 cells, with Hmox-1 being the most strongly upregulated gene. Collectively, our study indicates that TSPO ligands can enhance the Nrf2 antioxidant pathway in RPE cells and protect them from cellular damage resulting from inflammation and oxidative stress. (C) 2020 The Authors. Published by Elsevier Inc.
C1 [Rashid, Khalid; Verhoyen, Mathilde; Taiwo, Moyinoluwa; Langmann, Thomas] Univ Cologne, Fac Med, Dept Ophthalmol, Lab Expt Immunol Eye, D-50931 Cologne, Germany.
   [Rashid, Khalid; Verhoyen, Mathilde; Taiwo, Moyinoluwa; Langmann, Thomas] Univ Cologne, Univ Hosp Cologne, D-50931 Cologne, Germany.
   [Verhoyen, Mathilde] Univ Namur, Fac Med, Biomed Sci Dept, B-615000 Namur, Belgium.
   [Langmann, Thomas] Ctr Mol Med Cologne CMMC, D-50931 Cologne, Germany.
C3 University of Cologne; University of Cologne; University of Namur;
   University of Cologne
RP Langmann, T (通讯作者)，Univ Cologne, Dept Ophthalmol, Lab Expt Immunol Eye, Joseph Stelzmann Str 9, D-50931 Cologne, Germany.
EM krashid@mednet.ucla.edu; mathilde.verhoyen@gmail.com;
   moyinoluwa.taiwo@uk-koeln.de; thomas.langmann@uk-koeln.de
OI Rashid, Khalid/0000-0002-5070-8010
FU Velux Foundation; German Academic Exchange Service (DAAD); Deutsche
   Forschungsgemeinschaft [FOR2240]; Center for Molecular Medicine Cologne
FX This study was funded by the Velux Foundation, the German Academic
   Exchange Service (DAAD), and the Deutsche Forschungsgemeinschaft
   (FOR2240 project 6), and the Center for Molecular Medicine Cologne
   (Project B05).
CR Akhtar-Schafer I, 2018, EMBO MOL MED, V10, DOI 10.15252/emmm.201708259
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NR 29
TC 3
Z9 3
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUL 23
PY 2020
VL 528
IS 2
BP 261
EP 268
DI 10.1016/j.bbrc.2020.05.114
PG 8
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA LY7NU
UT WOS:000540715000004
PM 32482385
OA hybrid
DA 2022-11-30
ER

PT J
AU Xiong, YZ
   Kwon, M
   Bittner, AK
   Virgili, G
   Giacomelli, G
   Legge, GE
AF Xiong, Ying-Zi
   Kwon, MiYoung
   Bittner, Ava K.
   Virgili, Gianni
   Giacomelli, Giovanni
   Legge, Gordon E.
TI Relationship Between Acuity and Contrast Sensitivity: Differences Due to
   Eye Disease
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE visual acuity; contrast sensitivity; eye disease
ID VISUAL RISK-FACTORS; MACULAR DEGENERATION; SUBTLE DISTURBANCES; OLDER
   DRIVERS; LOW-VISION; RELIABILITY; IMPAIRMENT; GLAUCOMA; INVOLVEMENT;
   HISTORY
AB PURPOSE. Visual acuity (VA) and contrast sensitivity (CS) characterize different aspects of visual function. Whereas VA is a standard test in routine eye exams and clinical trials, CS is often not included. We investigated the pathology-specific dissociation between VA and CS by quantifying and comparing the relationship between these two measures in common ocular pathologies.
   METHODS. VA and CS data were assembled from 1113 subjects, including groups with cataract (n = 450), age-related macular degeneration (AMD; n = 232), glaucoma (n = 100), retinitis pigmentosa (RP; n = 87), and normal ocular health (n = 244). VA and CS were measured by the Early Treatment Diabetic Retinopathy Study chart and Pelli-Robson chart, respectively.
   RESULTS. Even when VA was relatively normal (<0.3 logMAR), the four ocular pathology groups showed quantitatively different mean CS deficits relative to normal controls, ranging from -0.01 log units for cataract to 0.23 log units for RP. When the entire range of VA was considered, the corresponding deficits in CS were noticeably different across these four groups, being least for cataract and progressively more severe for glaucoma, AMD, and RP. For every 1.0 logMAR loss of VA, the corresponding deficit in CS ranged from 0.22 logCS for cataract to 0.97 logCS for RP.
   CONCLUSIONS. The quantitative relationship between VA and CS depends on the ocular pathology. CS appears to provide valuable complementary information to VA in the early detection of eye disease and when evaluating visual impairment.
C1 [Xiong, Ying-Zi; Legge, Gordon E.] Univ Minnesota, Dept Psychol, 75 E River Rd, Minneapolis, MN 55455 USA.
   [Kwon, MiYoung] Univ Alabama Birmingham, Dept Ophthalmol & Visual Sci, Birmingham, AL USA.
   [Bittner, Ava K.] Univ Calif Los Angeles, Dept Ophthalmol, Stein Eye Inst, Los Angeles, CA USA.
   [Bittner, Ava K.] Nova Southeastern Univ, Coll Optometry, Davie, FL USA.
   [Bittner, Ava K.] Johns Hopkins Univ, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21218 USA.
   [Virgili, Gianni; Giacomelli, Giovanni] Univ Florence, Dept Neurosci Psychol Drug Res & Childs Hlth, Florence, Italy.
C3 University of Minnesota System; University of Minnesota Twin Cities;
   University of Alabama System; University of Alabama Birmingham;
   University of California System; University of California Los Angeles;
   Nova Southeastern University; Johns Hopkins University; Johns Hopkins
   Medicine; University of Florence
RP Xiong, YZ (通讯作者)，Univ Minnesota, Dept Psychol, 75 E River Rd, Minneapolis, MN 55455 USA.
EM yingzi@umn.edu
RI giacomelli, giovanni/ABC-6173-2020; Bittner, Ava/AAK-8778-2021; Virgili,
   Gianni/P-6607-2014
OI Bittner, Ava/0000-0002-9498-2230; Virgili, Gianni/0000-0002-9960-2989;
   Legge, Gordon/0000-0002-3742-1680
FU National Institutes of Health [R01 EY002934, R01 EY027857]; Research to
   Prevent Blindness/Lions Clubs International Foundation low vision
   research award; National Eye Institute [K23 EY018356, R21 EY023720, P30
   NR008995]; Foundation Fighting Blindness; National Institute on Aging
   [P50 AG11684]; Envision Fellowship from the Envision Research Institute
FX Supported by Grants from the National Institutes of Health (R01 EY002934
   to GEL; R01 EY027857 to MK), by the Envision Fellowship from the
   Envision Research Institute (Y-ZX), by a Research to Prevent
   Blindness/Lions Clubs International Foundation low vision research award
   (to MK), by grants from the National Eye Institute (K23 EY018356 to AKB;
   R21 EY023720 and P30 NR008995 to AKB), and by the Foundation Fighting
   Blindness. The authors thank Cynthia Owsley for sharing data (supported
   by National Institute on Aging grant P50 AG11684) and for commenting on
   our manuscript.
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NR 60
TC 9
Z9 9
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 JUN
PY 2020
VL 61
IS 6
AR 40
DI 10.1167/iovs.61.6.40
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MD7MJ
UT WOS:000544154500041
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, Y
   Zhao, L
   Lu, F
   Yang, X
   Deng, QC
   Ji, BP
   Huang, FH
AF Wang, Yong
   Zhao, Liang
   Lu, Feng
   Yang, Xue
   Deng, Qianchun
   Ji, Baoping
   Huang, Fenghong
TI Retinoprotective Effects of Bilberry Anthocyanins via Antioxidant,
   Anti-Inflammatory, and Anti-Apoptotic Mechanisms in a Visible
   Light-Induced Retinal Degeneration Model in Pigmented Rabbits
SO MOLECULES
LA English
DT Article
DE retinoprotection; bilberry anthocyanin; photoreceptor; light-induced
   retinal degeneration; pigmented rabbits
ID ROD OUTER SEGMENTS; INDUCED DAMAGE; PHOTOCHEMICAL DAMAGE; MACULAR
   DEGENERATION; BLUE; VISION; NEUROPROTECTION; PERMEABILITY; ACTIVATION;
   CELLS
AB Excessive visible light exposure can induce damage to retinal cells and contribute to the development or progression of age-related macular degeneration. In this study we created a model of phototoxicity in pigmented rabbits. Furthermore, we investigated the protective effect of bilberry anthocyanin extract (BAE, Table A1) and explored the possible mechanisms of action in this model. The model of light-induced retinal damage was established by the pigmented rabbits exposed to light at 18,000 lx for 2 h, and they were sacrificed on day 7. After administration of BAE at dosages of 250 and 500 mg/kg/day, retinal dysfunction was significantly inhibited in terms of electroretinograms, and the decreased thicknesses of retinal outer nuclear layer and lengths of the outer segments of the photoreceptor cells were suppressed in rabbits with retinal degeneration. BAE attenuated the changes caused by light to certain apoptotic proteins (Bax, Bcl-2, and caspase-3). The extract increased the levels of superoxide dismutase, glutathione peroxidase, and catalase, as well as the total antioxidant capacity, but decreased the malondialdehyde level in the retinal cells. BAE inhibited the light-induced elevation in the levels of proinflammatory cytokines and angiogenic parameters (IL-1 and VEGF). Results showed that visible light-induced retinal degeneration model in pigmented rabbits was successfully established and BAE exhibited protective effects by increasing the antioxidant defense mechanisms, suppressing lipid peroxidation and proinflammatory cytokines, and inhibiting retinal cells apoptosis.
C1 [Wang, Yong; Zhao, Liang; Lu, Feng; Yang, Xue; Ji, Baoping] China Agr Univ, Coll Food Sci & Nutr Engn, Beijing Key Lab Funct Food Plant Resources, Beijing 100083, Peoples R China.
   [Deng, Qianchun; Huang, Fenghong] Chinese Acad Agr Sci, Oil Crops Res Inst, Wuhan 430062, Peoples R China.
   [Deng, Qianchun; Huang, Fenghong] Hubei Key Lab Lipid Chem & Nutr, Wuhan 430062, Peoples R China.
C3 China Agricultural University; Chinese Academy of Agricultural Sciences;
   Oil Crops Research Institute, CAAS
RP Ji, BP (通讯作者)，China Agr Univ, Coll Food Sci & Nutr Engn, Beijing Key Lab Funct Food Plant Resources, Beijing 100083, Peoples R China.
EM WangYongyffs@gmail.com; liangzhao@cau.edu.cn; 18201041642@163.com;
   13001994248@163.com; chunn2@163.com; wangyong@cau.edu.cn;
   HuangFengHong88@126.com
OI Zhao, Liang/0000-0003-2542-9279
FU Director Fund of Oil Crops Research Institute [1610172014006]; Open
   Foundation of Hubei Key Laboratory of Lipid Chemistry and Nutrition
   [2014002]
FX This work was financially supported by the Director Fund of Oil Crops
   Research Institute (1610172014006) and the Open Foundation of Hubei Key
   Laboratory of Lipid Chemistry and Nutrition (2014002).
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NR 54
TC 43
Z9 46
U1 0
U2 20
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1420-3049
J9 MOLECULES
JI Molecules
PD DEC
PY 2015
VL 20
IS 12
BP 22395
EP 22410
DI 10.3390/molecules201219785
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA DA1CH
UT WOS:000367533400104
PM 26694327
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Novikova, YP
   Gancharova, OS
   Eichler, OV
   Philippov, PP
   Grigoryan, EN
AF Novikova, Yu P.
   Gancharova, O. S.
   Eichler, O. V.
   Philippov, P. P.
   Grigoryan, E. N.
TI Preventive and therapeutic effects of SkQ1-containing Visomitin eye
   drops against light-induced retinal degeneration
SO BIOCHEMISTRY-MOSCOW
LA English
DT Review
DE retina; photoreceptors; photodamage; SkQ1; Visomitin
ID TARGETED PLASTOQUINONE DERIVATIVES; MACULAR DEGENERATION; INTERRUPT
   EXECUTION; OXIDATIVE STRESS; ALBINO-RATS; PIGMENT-EPITHELIUM; DAMAGE;
   MITOCHONDRIA; APOPTOSIS; CELLS
AB The human retina is constantly affected by light of varying intensity, this being especially true for photoreceptor cells and retinal pigment epithelium. Traditionally, photoinduced damages of the retina are induced by visible light of high intensity in albino rats using the LIRD (light-induced retinal degeneration) model. This model allows study of pathological processes in the retina and the search for retinoprotectors preventing retinal photodamage. In addition, the etiology and mechanisms of retina damage in the LIRD model have much in common with the mechanisms of the development of age-related retinal disorders, in particular, with age-related macular degeneration (AMD). We have studied preventive and therapeutic effects of Visomitin eye drops (based on the mitochondria-targeted antioxidant SkQ1) on albino rat retinas damaged by bright light. In the first series of experiments, rats receiving Visomitin for two weeks prior to illumination demonstrated significantly less expressed atrophic and degenerative changes in the retina compared to animals receiving similar drops with no SkQ1. In the second series, the illuminated rats were treated for two weeks with Visomitin or similar drops without SkQ1. The damaged retinas of the experimental animals were repaired much more effectively than those of the control animals. Therefore, we conclude that Visomitin SkQ1-containing eye drops have pronounced preventive and therapeutic effects on the photodamaged retina and might be recommended as a photoprotector and a pharmaceutical preparation for the treatment of AMD in combination with conventional medicines.
C1 [Novikova, Yu P.; Grigoryan, E. N.] Koltzov Inst Dev Biol, Moscow 119334, Russia.
   [Gancharova, O. S.; Eichler, O. V.; Philippov, P. P.] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119991, Russia.
C3 Russian Academy of Sciences; Koltzov Institute of Developmental Biology
   of the Russian Academy of Sciences; Lomonosov Moscow State University
RP Gancharova, OS (通讯作者)，Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119991, Russia.
EM leonore@mail.ru; olgancharova@gmail.com; fxb@genebee.msu.su
RI Eleonora, Grigoryan/AAG-8182-2021; Gancharova, Olga S/M-9980-2014
OI Gancharova, Olga S/0000-0001-7441-1062
FU Research Institute of Mitoengineering, Lomonosov Moscow State University
FX This work was financially supported by the Research Institute of
   Mitoengineering, Lomonosov Moscow State University.
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NR 55
TC 15
Z9 17
U1 0
U2 13
PU MAIK NAUKA/INTERPERIODICA/SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA
SN 0006-2979
EI 0320-9725
J9 BIOCHEMISTRY-MOSCOW+
JI Biochem.-Moscow
PD OCT
PY 2014
VL 79
IS 10
BP 1101
EP 1110
DI 10.1134/S0006297914100113
PG 10
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA AR7ID
UT WOS:000343751900011
PM 25519068
DA 2022-11-30
ER

PT J
AU Shields, CL
   Manalac, J
   Das, C
   Ferguson, K
   Shields, JA
AF Shields, Carol L.
   Manalac, Janet
   Das, Chandana
   Ferguson, Kyle
   Shields, Jerry A.
TI Choroidal melanoma: clinical features, classification, and top 10
   pseudomelanomas
SO CURRENT OPINION IN OPHTHALMOLOGY
LA English
DT Review
DE choroids; eye; melanoma; pseudomelanoma; tumor; uvea
ID OPTICAL COHERENCE TOMOGRAPHY; UVEAL MELANOMA; AUTOFLUORESCENCE;
   TRANSFORMATION; ASSOCIATION; METASTASIS; PREVALENCE; PROGNOSIS; NEVUS
AB Purpose of reviewTo review the current features and classification of choroidal melanoma, and to identify the lesions that clinically simulate choroidal melanoma (pseudomelanoma).Recent findingsUveal melanoma is a serious life-threatening intraocular malignancy, most often found in Caucasians (98%) and primarily involving the choroid (90%), ciliary body (7%), or iris (2%). This review will concentrate on choroidal melanoma. At diagnosis, choroidal melanoma usually appears as a pigmented (85%) tumor underlying the retina with a median basal dimension of 11mm and a mean thickness of 4.5mm. The American Joint Committee on Cancer classification allows for categorization and staging of melanoma. Following ocular therapy, adjuvant systemic therapy is provided for patients with high-risk melanoma who demonstrate alterations in chromosomes 3, 6, and 8 or those with class 2 on gene-expression profiling, detected by needle biopsy or solid tumor biopsy. The prognosis of choroidal melanoma depends most importantly on the genetic alterations and tumor size. Every millimeter increase in thickness leads to a 5% increased risk for metastasis. The leading conditions that simulate choroidal melanoma include choroidal nevus, peripheral exudative hemorrhagic chorioretinopathy, congenital hypertrophy of the retinal pigment epithelium (RPE), hemorrhagic RPE detachment, choroidal hemangioma, age-related macular degeneration, RPE hyperplasia, and others. These pseudomelanomas can be differentiated from choroidal melanoma by their unique clinical features.SummaryChoroidal melanoma is a serious malignancy with characteristic features. Early detection and therapy is important. Pseudomelanomas can lead to diagnostic confusion; however, clinical features aid in differentiation.
C1 [Shields, Carol L.; Manalac, Janet; Das, Chandana; Ferguson, Kyle; Shields, Jerry A.] Thomas Jefferson Univ, Wills Eye Hosp, Ocular Oncol Serv, Philadelphia, PA 19107 USA.
C3 Jefferson University
RP Shields, CL (通讯作者)，Wills Eye Inst, Ocular Oncol Serv, Suite 1440,840 Walnut St, Philadelphia, PA 19107 USA.
EM carolshields@gmail.com
FU Eye Tumor Research Foundation, Philadelphia, PA; Lift for a Cure,
   Morrisville, PA
FX This work was supported by the Eye Tumor Research Foundation,
   Philadelphia, PA (C. L. S. and J.A.S.) and Lift for a Cure, Morrisville,
   PA (C. L. S. and J.A.S.). None
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NR 33
TC 58
Z9 62
U1 1
U2 26
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8738
EI 1531-7021
J9 CURR OPIN OPHTHALMOL
JI Curr. Opin. Ophthalmol.
PD MAY
PY 2014
VL 25
IS 3
BP 177
EP 185
DI 10.1097/ICU.0000000000000041
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AF1GC
UT WOS:000334461400005
PM 24614143
DA 2022-11-30
ER

PT J
AU Schellmann, N
   Panjideh, H
   Fasold, P
   Bachran, D
   Bachran, C
   Deckert, PM
   Fuchs, H
AF Schellmann, Nicole
   Panjideh, Hossein
   Fasold, Patricia
   Bachran, Diana
   Bachran, Christopher
   Deckert, Peter M.
   Fuchs, Hendrik
TI Targeted Tumor Therapy With a Fusion Protein of an Antiangiogenic Human
   Recombinant scFv and Yeast Cytosine Deaminase
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE ADEPT; ED-B; L19; prodrug; targeted tumor therapy
ID ED-B DOMAIN; SINGLE-CHAIN ANTIBODY; ANGIOGENESIS; EXPRESSION; MARKER;
   FIBRONECTIN; FRAGMENT; DELIVERY; AFFINITY; SAPONIN
AB In adults, endothelial cell division occurs only in wound healing, during menstruation, or in diseases such as wet age-related macular degeneration or development of benign or malignant tissues. Angiogenesis is one of the major requirements to supply the fast developing tumor tissue with oxygen and nutrients, and enables it to spread into other tissues far from its origin. We selected the extradomain B (ED-B), a splice variant of fibronectin, which is exclusively expressed in ovaries, uterus, during wound healing, and in tumor tissues, as a target for the development of an innovative antiangiogenic, prodrug-based targeted tumor therapy approach. We designed a fusion protein termed L19CDy-His, consisting of the antibody single chain fragment L19 for targeting ED-B and yeast cytosine deaminase for the conversion of 5-fluorocytosine into cytotoxic 5-fluorouracil. We purified high amounts of the fusion protein from Pichia pastoris that is stable, enzymatically active, and retains 75% of its activity after incubation with human plasma for up to 72 hours. The binding of L19CDy-His to ED-B was confirmed by an enzyme-linked immunosorbent assay and quantified by surface plasmon resonance spectroscopy determining a KD value of 81 +/- 7 nM. L19CDy-His successfully decreased cell survival of the murine ED-B-expressing teratocarcinoma cell line F9 upon addition of the prodrug 5-fluorocytosine. Our data demonstrate the suitability of targeting ED-B by L19CDy-His for effective prodrug-based tumor therapy.
C1 [Schellmann, Nicole; Fasold, Patricia; Bachran, Diana; Bachran, Christopher; Fuchs, Hendrik] Charite, Inst Labs Med Klin Chem & Pathobiochem, D-12200 Berlin, Germany.
   [Panjideh, Hossein] Max Delbruck Ctr Mol Med MDC, Dept Mol Tumor Genet & Immunogenet, Berlin, Germany.
   [Fasold, Patricia] InVivo BioTech Serv GmbH, Hennigsdorf, Germany.
   [Deckert, Peter M.] Stadt Klinikum Brandenburg GmbH, Innere Med Gastroenterologie Onkol 2, Brandenburg, Germany.
   [Bachran, Christopher] NIAID, NIH, Bethesda, MD 20892 USA.
C3 Free University of Berlin; Humboldt University of Berlin; Charite
   Universitatsmedizin Berlin; Helmholtz Association; Max Delbruck Center
   for Molecular Medicine; National Institutes of Health (NIH) - USA; NIH
   National Institute of Allergy & Infectious Diseases (NIAID)
RP Fuchs, H (通讯作者)，Charite, Inst Labs Med Klin Chem & Pathobiochem, Campus Benjamin Franklin,Hindenburgdamm 30, D-12200 Berlin, Germany.
EM hendrik.fuchs@charite.de
RI Fuchs, Hendrik/AAE-7379-2019; Deckert, P Markus/AAU-6424-2020
OI Fuchs, Hendrik/0000-0001-9153-9594; Bachran, Diana/0000-0001-9203-4862
FU Deutsche Krebshilfe [108492]; Kommission fur wissenschaftliche
   Nachwuchsforderung und Weiterbildung, Charite-Universitats-medizin
   Berlin
FX Supported by grants from Deutsche Krebshilfe (108492) and the Kommission
   fur wissenschaftliche Nachwuchsforderung und Weiterbildung,
   Charite-Universitats-medizin Berlin.
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NR 34
TC 3
Z9 3
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1524-9557
EI 1537-4513
J9 J IMMUNOTHER
JI J. Immunother.
PD SEP
PY 2012
VL 35
IS 7
BP 570
EP 578
DI 10.1097/CJI.0b013e31826b1fb4
PG 9
WC Oncology; Immunology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Immunology; Research & Experimental Medicine
GA 997AG
UT WOS:000308135700005
PM 22892453
DA 2022-11-30
ER

PT J
AU Dai, TH
   Fuchs, BB
   Coleman, JJ
   Prates, RA
   Astrakas, C
   St Denis, TG
   Ribeiro, MS
   Mylonakis, E
   Hamblin, MR
   Tegos, GP
AF Dai, Tianhong
   Fuchs, Beth B.
   Coleman, Jeffrey J.
   Prates, Renato A.
   Astrakas, Christos
   St Denis, Tyler G.
   Ribeiro, Martha S.
   Mylonakis, Eleftherios
   Hamblin, Michael R.
   Tegos, George P.
TI Concepts and principles of photodynamic therapy as an alternative
   antifungal discovery platform
SO FRONTIERS IN MICROBIOLOGY
LA English
DT Review
DE photodynamic inactivation; photodynamic therapy; photosensitizer;
   reactive oxygen species; permeability barrier; multidrug efflux systems;
   biofilms; clinical applications
ID DERMATOPHYTE TRICHOPHYTON-RUBRUM; RESISTANT CANDIDA-ALBICANS; IN-VITRO;
   METHYLENE-BLUE; CHOROIDAL NEOVASCULARIZATION; SACCHAROMYCES-CEREVISIAE;
   TRANSPLANT RECIPIENTS; 5-AMINOLEVULINIC ACID; MK-0991 L-743,872;
   FUNGAL-INFECTIONS
AB Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative antifungal countermeasures. Photodynamic therapy (PDT) was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Antifungal PDT is an area of increasing interest, as research is advancing (i) to identify the photochemical and photophysical mechanisms involved in photoinactivation; (ii) to develop potent and clinically compatible photosensitizers; (iii) to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; (iv) to explore novel photosensitizer delivery platforms; and (v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants.
C1 [Dai, Tianhong; St Denis, Tyler G.; Hamblin, Michael R.; Tegos, George P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
   [Dai, Tianhong; Hamblin, Michael R.; Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
   [Fuchs, Beth B.; Coleman, Jeffrey J.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
   [Prates, Renato A.; Ribeiro, Martha S.] IPEN CNEN SP, Ctr Lasers & Applicat, Sao Paulo, Brazil.
   [Astrakas, Christos] Democritus Univ Thrace, Sch Med, Div Internal Med, Alexandroupolis, Greece.
   [St Denis, Tyler G.] Columbia Univ, Dept Chem, New York, NY 10027 USA.
   [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   [Tegos, George P.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA.
   [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA.
C3 Harvard University; Massachusetts General Hospital; Harvard University;
   Harvard Medical School; Harvard University; Massachusetts General
   Hospital; Comissao Nacional de Energia Nuclear (CNEN); Instituto de
   Pesquisas Energeticas e Nucleares (IPEN); Democritus University of
   Thrace; Columbia University; Harvard University; Massachusetts Institute
   of Technology (MIT); University of New Mexico; University of New Mexico
RP Tegos, GP (通讯作者)，Univ New Mexico, Ctr Mol Discovery, UNM Hlth Sci Ctr, Sch Med,Dept Pathol, 2325 Camino Salud,CRF 217A MSC 07-4025, Albuquerque, NM 87131 USA.
EM gtegos@salud.unm.edu
RI Hamblin, Mike/AAB-2511-2022; Hamblin, Michael R/H-2758-2019; Prates,
   Renato A/F-8235-2014; Ribeiro, Martha Simões/G-3517-2012; Dai,
   Tianhong/P-5961-2018; Coleman, Jeffrey J/E-2981-2015; Langenheder,
   Silke/C-9614-2017; Berga, Merce/E-3305-2018
OI Hamblin, Michael R/0000-0001-6431-4605; Prates, Renato
   A/0000-0002-8115-9237; Ribeiro, Martha Simões/0000-0002-4203-1134; Dai,
   Tianhong/0000-0001-8960-8896; Coleman, Jeffrey/0000-0001-8579-1996;
   Lennon, Jay T./0000-0003-3126-6111; Langenheder,
   Silke/0000-0002-5245-9935; Schmidt, Thomas/0000-0002-8209-6055; Berga,
   Merce/0000-0002-9518-8776; Burgmann, Helmut/0000-0002-5651-5906;
   Saint-Denis, Tyler/0000-0002-9152-2415; Martiny,
   Jennifer/0000-0002-2415-1247; Shade, Ashley/0000-0002-7189-3067; Dolan,
   Kristin/0000-0003-2642-9406
FU NIH [5U54M11084690-02, RO1 AI050875]; US Air Force MFEL Program
   [FA9550-04-1-0079]; Bullock-Wellman Fellowship Award; Airlift Research
   Foundation Extremity Trauma Research Grant [109421]; Columbia University
   I. I. Rabi Fellows Program; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS
   DISEASES [R01AI050875, T32AI007061] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF MENTAL HEALTH [U54MH084690] Funding Source: NIH
   RePORTER
FX George P. Tegos is supported by the NIH (grant 5U54M11084690-02).
   Research conducted in the Hamblin Laboratory was supported by NIH (RO1
   AI050875 to MRH) and US Air Force MFEL Program (FA9550-04-1-0079).
   Research conducted in the Mylonakis Laboratory was supported by NIH (RO1
   AI050875 to Eleftherios Mylonakis) and, Tianhong Dai was partially
   supported by a Bullock-Wellman Fellowship Award and an Airlift Research
   Foundation Extremity Trauma Research Grant (grant 109421). Research
   conducted by Tyler G. St. Denis is supported by the Columbia University
   I. I. Rabi Fellows Program.
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NR 150
TC 394
Z9 404
U1 13
U2 29
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1664-302X
J9 FRONT MICROBIOL
JI Front. Microbiol.
PY 2012
VL 3
AR 120
DI 10.3389/fmicb.2012.00120
PG 16
WC Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Microbiology
GA V31DF
UT WOS:000208863600172
PM 23267351
OA gold, Green Published
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Bermejo, JL
   Perez, AG
   Brandt, A
   Hemminki, K
   Matthews, AG
AF Lorenzo Bermejo, Justo
   Garcia Perez, Alfonso
   Brandt, Andreas
   Hemminki, Kari
   Matthews, Abigail G.
TI Comparison of Six Statistics of Genetic Association Regarding Their
   Ability to Discriminate between Causal Variants and Genetically Linked
   Markers
SO HUMAN HEREDITY
LA English
DT Article
DE Common-disease common-variant hypothesis; Markers; Causal susceptibility
   variants; Case-control study; Genetic association; Familial relative
   risk
ID GENOME-WIDE ASSOCIATION; MISSING HERITABILITY; LOGISTIC-REGRESSION;
   COMMON VARIANTS; STRATEGIES; DISEASE; TRAITS; FIT
AB Objectives: Genome-wide association (GWA) studies still rely on the common-disease common-variant hypothesis since the assumption is associated with increased power. In GWA studies, polymorphisms are genotyped and their association with disease is investigated. Most of the identified associations are indirect and reflect a shared inheritance of the genotyped markers and genetically linked causal variants. We have compared six statistics of genetic association regarding their ability to discriminate between markers and causal susceptibility variants, including a probability value (Pval) and a Bayes Factor (BF) based on logistic regression, and the attributable familial relative risk (FRR). Methods: We carried out a simulation-based sensitivity analysis to explore several conceivable scenarios. Theoretical results were illustrated by established causal associations with age-related macular degeneration and by using imputed data based on HapMap for a case-control study of breast cancer. Results: Our data indicate that a representation of genetic association by FRRs and BFs generally facilitates the distinction of causal variants. The FRR showed the best discriminative power under most investigated scenarios, but no single statistic outperformed the others in all situations. For example, rare moderate-to low-penetrance variants (allele frequency: 1%, dominant odds ratio: <= 2.0) seem to be best discriminated by BFs. Conclusions: Present results may help to fully utilize the data generated in association studies that take advantage of next generation sequencing and/or multiple imputation based on the 1000 Genomes Project. Copyright (C) 2011 S. Karger AG, Basel
C1 [Lorenzo Bermejo, Justo] Univ Heidelberg Hosp, Inst Med Biometry & Informat, DE-69120 Heidelberg, Germany.
   [Lorenzo Bermejo, Justo; Hemminki, Kari] German Canc Res Ctr, Div Mol Genet Epidemiol, INF 520, D-6900 Heidelberg, Germany.
   [Garcia Perez, Alfonso] Spanish Open Univ UNED, Dept Stat, Madrid, Spain.
   [Hemminki, Kari] Lund Univ, Ctr Primary Care Res, Malmo, Sweden.
   [Matthews, Abigail G.] Rockefeller Univ, Ott Lab, New York, NY 10021 USA.
   [Matthews, Abigail G.] EMMES Corp, Rockville, MD USA.
C3 Ruprecht Karls University Heidelberg; Helmholtz Association; German
   Cancer Research Center (DKFZ); Universidad Nacional de Educacion a
   Distancia (UNED); Lund University; Rockefeller University; Emmes
   Corporation
RP Bermejo, JL (通讯作者)，Univ Heidelberg Hosp, Inst Med Biometry & Informat, INF 305, DE-69120 Heidelberg, Germany.
EM Justo.Lorenzo@imbi.uni-heidelberg.de
RI García-Pérez, Alfonso/H-2534-2015
OI García-Pérez, Alfonso/0000-0002-6066-4138; Lorenzo Bermejo,
   Justo/0000-0002-6568-5333
FU Deutsche Forschungsgemeinschaft (DFG) [SFB/TRR77, Z2]
FX This work was supported by a grant from the Deutsche
   Forschungsgemeinschaft (DFG, SFB/TRR77, project Z2).
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NR 32
TC 3
Z9 3
U1 0
U2 5
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0001-5652
EI 1423-0062
J9 HUM HERED
JI Hum. Hered.
PY 2011
VL 72
IS 2
BP 142
EP 152
DI 10.1159/000332006
PG 11
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 842AO
UT WOS:000296558000007
PM 22025134
OA Bronze
DA 2022-11-30
ER

PT J
AU Hara, R
   Inomata, Y
   Kawaji, T
   Sagara, N
   Inatani, M
   Fukushima, M
   Tanihara, H
AF Hara, Ryuhei
   Inomata, Yasuya
   Kawaji, Takahiro
   Sagara, Nina
   Inatani, Masaru
   Fukushima, Mikiko
   Tanihara, Hidenobu
TI Suppression of Choroidal Neovascularization by N-Acetyl-Cysteine in Mice
SO CURRENT EYE RESEARCH
LA English
DT Article
DE 4-Hydroxy-2-nonenal-modified protein; Age-related macular degeneration;
   Choroidal neovascularization; N-acetyl-cysteine; Nucleus factor-kappa B;
   Oxidative stress; Vascular endothelial growth factor
ID ENDOTHELIAL GROWTH-FACTOR; OXIDATIVE STRESS; KAPPA-B; MACULAR
   DEGENERATION; DOWN-REGULATION; REDOX STATUS; ACETYLCYSTEINE; VEGF;
   MACROPHAGES; CELLS
AB Methods: CNV was induced in C57BL/6 mice by laser photocoagulation of the ocular fundus. Mice were injected intraperitoneally with NAC or vehicle alone. The levels of 4-hydoroxy-2-nonenal (4-HNE)-modified protein and nucleus factor (NF)-kappa B were determined by wester blotting. The recruitment of macrophages and neutrophils after laser injury was analyzed immunohistochemically and in myeloperoxidase (MPO) assays. Enzyme-linked immunosorbent assays (ELISA) were used to measure monocyte chemotactic protein (MCP)-1, CXCL1, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1, and VEGFR-2. The extent of CNV was evaluated 7 d after laser injury by lectin staining.
   Results: In NAC-treated mice with laser-induced injuries, the induction of 4-HNE-modified protein after 3 hr and the activation of NF-kappa B in nuclear extracts after 6 hr were markedly suppressed compared to vehicle-treated mice. Macrophage and neutrophil recruitment were inhibited and the levels of MCP-1, CXCL1, VEGF, and VEGFR-1 were also lower in NAC-treated mice compared to vehicle-treated mice. Furthermore, the extent of CNV induced was significantly lower in NAC-treated compared to vehicle-treated mice (p = 0.027).
   Conclusions: Our results clearly showed that NAC inhibited indicators of oxidative stress and the activation of NF-kappa B induced by laser injury, and, consequently, suppressed macrophage and neutrophil infiltration and the development of CNV. This suggests novel preventative and interventional therapeutic strategies for age-related macular degeneration.
C1 [Hara, Ryuhei; Inomata, Yasuya; Kawaji, Takahiro; Sagara, Nina; Inatani, Masaru; Fukushima, Mikiko; Tanihara, Hidenobu] Kumamoto Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Kumamoto 8608556, Japan.
C3 Kumamoto University
RP Inomata, Y (通讯作者)，Kumamoto Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Honjo 1-1-1, Kumamoto 8608556, Japan.
EM inoyas@kxb.biglobe.ne.jp
RI Kawaji, Takahiro/AAH-2481-2020
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NR 45
TC 19
Z9 20
U1 0
U2 1
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
PY 2010
VL 35
IS 11
BP 1012
EP 1020
DI 10.3109/02713683.2010.500112
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 667AK
UT WOS:000283164600009
PM 20958190
DA 2022-11-30
ER

PT J
AU Sasahara, M
   Otani, A
   Yodoi, Y
   Yoshimura, N
AF Sasahara, Manabu
   Otani, Atsushi
   Yodoi, Yuko
   Yoshimura, Nagahisa
TI Circulating Hematopoietic Stem Cells in Patients with Idiopathic
   Choroidal Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL PROGENITOR CELLS; SUBRETINAL NEOVASCULARIZATION;
   PHOTODYNAMIC THERAPY; MACULAR DEGENERATION; YOUNG-PATIENTS;
   ANGIOGENESIS; REPAIR; DIFFERENTIATE; PATHOGENESIS; SYSTEM
AB PURPOSE. In a prior study, the correlation was investigated between circulating hematopoietic stem cells (HSCs) and the activity or severity of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). The present study was designed to explore the role of circulating HSCs in the pathogenesis of CNV in patients with idiopathic (i)CNV.
   METHODS. Thirteen patients with clinically documented iCNV and 10 age-sex matched patients without iCNV or systemic disease were enrolled in a case-control study. Circulating HSCs were collected from the patients' peripheral blood and cultured. Colony-forming capacity, migration activity, and invasion activity of HSCs were experimentally analyzed.
   RESULTS. Colony-forming units by Hill's assay (CFU-Hill) were markedly lower (P < 0.001) in patients with iCNV (12.8 +/- 3.2) than in healthy patients (67.6 +/- 12.6). Invasion activities of HSCs were reduced significantly in patients with iCNV. CFU-Hill was impaired in the patients (4.0 +/- 1.2) with CNV more than 1500 mu m compared with the patients (20.3 +/- 4.0) with CNV less than 1500 mu m (P = 0.006).
   CONCLUSIONS. Similar to the previous finding of CNV associated with AMD, impaired functional activities of circulating HSCs were observed in patients with iCNV, which correlated with the size of iCNV. These results in young patients provide evidence to support the role of circulating HSCs in the pathogenesis of CNV. (Invest Ophthalmol Vis Sci. 2009; 50: 1575-1579) DOI:10.1167/iovs.08-1900
C1 [Otani, Atsushi] Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Sakyo Ku, Kyoto 6068386, Japan.
C3 Kyoto University
RP Otani, A (通讯作者)，Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068386, Japan.
EM otan@kuhp.kyoto-u.ac.jp
FU Ministry of Education, Science, Sports and Culture, Japan [17689045]
FX Supported by Grant-in-aid 17689045 from the Ministry of Education,
   Science, Sports and Culture, Japan.
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NR 33
TC 11
Z9 12
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 APR
PY 2009
VL 50
IS 4
BP 1575
EP 1579
DI 10.1167/iovs.08-1900
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 424CP
UT WOS:000264543400014
PM 18806291
DA 2022-11-30
ER

PT J
AU Nguyen, TT
   Kreis, AJ
   Kawasaki, R
   Wang, JJ
   Seifert, BU
   Vilser, W
   Nagel, E
   Wong, TY
AF Nguyen, Thanh T.
   Kreis, Andreas J.
   Kawasaki, Ryo
   Wang, Jie Jin
   Seifert, Bernd-U.
   Vilser, Walthard
   Nagel, Edgar
   Wong, Tien Y.
TI Reproducibility of the Retinal Vascular Response to Flicker Light in
   Asians
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Diffuse Luminace Flicker; Reproducibility; Retinal Vascular Imaging;
   Auto regulation; Vasodilation
ID NITRIC-OXIDE; DIABETIC-RETINOPATHY; VESSEL DIAMETER; OPTIC-NERVE;
   CALIBER; RISK; STIMULATION; DISEASE
AB Purpose: Dilation of retinal vessels in response to diffuse luminance flicker may reflect endothelial function. Although this has previously been shown to be reproducible in whites, there have been no similar data in Asians. We assess the reproducibility of repeated measurements of this response in Asians.
   Material and Methods: Healthy Asians (n=33) with normal vision and no history of glaucoma, age related macular degeneration, cataract, or retinal arterial/venous occlusion participated in this study. Repeated measures from the same subjects were taken 30-60 min apart using the Dynamic Vessel Analyser (DVA, IMEDOS, Jena, Germany). Modification was made to the shape of the light source for Asian participants. Correlations of the first and second measures were assessed using Pearson correlation (R-2), and agreement between the two measures was shown using Bland-Altman plots.
   Results: After modification to the shape of the light source, almost perfect correlation was found between the 1st and 2nd measurements of baseline arteriolar (R-2=0.95) and venular diameters (R-2=0.98) of arteriolar maximum dilation (R-2=0.85). Substantially high correlation between the 1st and 2nd measurements of venular maximum dilation was found (R-2=0.80).
   Conclusions: Measurements of the dilation response of retinal vessels to diffuse luminance flicker an Asian sample using the DVA show high reproducibility for repeated measures over a short period of time. Such measurements may allow non-invasive quantification of endothelial function to study its association with systemic and ocular diseases.
C1 [Nguyen, Thanh T.; Kreis, Andreas J.; Kawasaki, Ryo; Wang, Jie Jin; Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.
   [Wang, Jie Jin] Univ Sydney, Westmead Millennium Inst, Ctr Vis Res, Sydney, NSW 2006, Australia.
   [Seifert, Bernd-U.; Vilser, Walthard] IMEDOS, Jena, Germany.
   [Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117595, Singapore.
C3 Centre for Eye Research Australia; University of Melbourne; University
   of Sydney; Westmead Institute for Medical Research; National University
   of Singapore; Singapore National Eye Center
RP Nguyen, TT (通讯作者)，Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia.
EM bittet@yahoo.com
RI Wong, Tien Yin/AAC-9724-2020; Wang, Jie Jin/P-1499-2014; Kawasaki,
   Ryo/H-9716-2019; Kawasaki, Ryo/B-7266-2009; wang, jie/GRS-0942-2022
OI Wong, Tien Yin/0000-0002-8448-1264; Wang, Jie Jin/0000-0001-9491-4898;
   Kawasaki, Ryo/0000-0002-7492-6303; 
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NR 21
TC 21
Z9 21
U1 0
U2 9
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 12
BP 1082
EP 1088
DI 10.3109/02713680903353764
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 531ON
UT WOS:000272677400010
PM 19958128
OA Green Published
DA 2022-11-30
ER

PT J
AU Mitchell, J
   Wolffsohn, J
   Woodcock, A
   Anderson, SJ
   Ffytche, T
   Rubinstein, M
   Amoaku, W
   Bradley, C
AF Mitchell, Jan
   Wolffsohn, James
   Woodcock, Alison
   Anderson, Stephen J.
   Ffytche, Timothy
   Rubinstein, Martin
   Amoaku, Winfried
   Bradley, Clare
TI The MacDQoL individualized measure of the impact of macular degeneration
   on quality of life: Reliability and responsiveness
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID DISEASE; DESIGN
AB PURPOSE: To investigate the MacDQoL test-retest reliability and sensitivity to change in vision over a period of one year in a sample of patients with age-related macular degeneration (AMD).
   DESIGN: A prospective, observational study.
   METHOD: Patients with AMD from an ophthalmologist's list (n = 135) completed the MacDQoL questionnaire by telephone interview and underwent a vision assessment on two occasions, one year apart.
   RESULTS: Among participants whose vision was stable over one year (n = 87), MacDQoL scores at baseline and follow-up were highly correlated (r = 0.95; P < .0001). Twelve of the 22 scale items had intraclass correlations of >.80; only two were correlated <.7. There was no difference between baseline and follow-up scores (P = .85), indicating excellent test-retest reliability. Poorer quality of life (QoL) at follow-up, measured by the MacDQoL present QoL overview item, was associated with deterioration in both the better eye and binocular distance visual acuity [VA] (r = 0.29; P = .001, r = 0.21; P = .016, respectively; n = 135). There was a positive correlation between deterioration in the Mac. DQoL average weighted impact score and deterioration in both binocular near VA and reading speed (r = 0.20; P = .019, r = 0.18; P = .041, respectively; n = 135).
   CONCLUSION: The MacDQoL has excellent test-retest reliability. Its sensitivity to change in vision status was demonstrated in correlational analyses. The measure indicates that the negative impact of AMD on QoL increases with increasing severity of visual impairment.
C1 [Mitchell, Jan; Woodcock, Alison; Bradley, Clare] Univ London, Dept Psychol, Egham TW20 0EX, Surrey, England.
   [Wolffsohn, James; Anderson, Stephen J.] Aston Univ, Sch Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England.
   [Ffytche, Timothy] London Sch Hyg & Trop Med, London WC1, England.
   [Rubinstein, Martin; Amoaku, Winfried] Queens Med Ctr, Dept Ophthalmol, Nottingham NG7 2UH, England.
C3 University of London; Royal Holloway University London; Aston
   University; University of London; London School of Hygiene & Tropical
   Medicine; University of Nottingham
RP Mitchell, J (通讯作者)，Univ London, Dept Psychol, Egham TW20 0EX, Surrey, England.
EM j.mitchell@rhul.ac.uk
OI Bradley, Clare/0000-0002-4079-0364; Amoaku,
   Winfried/0000-0001-5028-7984; Wolffsohn, James/0000-0003-4673-8927
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NR 21
TC 30
Z9 32
U1 0
U2 5
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 SEP
PY 2008
VL 146
IS 3
BP 447
EP 454
DI 10.1016/j.ajo.2008.04.031
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 343VR
UT WOS:000258883900019
PM 18547542
DA 2022-11-30
ER

PT J
AU Cashman, SM
   Sadowski, SL
   Morris, DJ
   Frederick, J
   Kumar-Singh, R
AF Cashman, SM
   Sadowski, SL
   Morris, DJ
   Frederick, J
   Kumar-Singh, R
TI Intercellular trafficking of adenovirus-delivered HSVVP22 from the
   retinal pigment epithelium to the photoreceptors - Implications for gene
   therapy
SO MOLECULAR THERAPY
LA English
DT Article
DE VP22; herpes simplex virus; adenovirus; retina; photoreceptor
ID ANTENNAPEDIA HOMEOBOX PEPTIDE; HUMAN IMMUNODEFICIENCY VIRUS; VP22-GFP
   FUSION PROTEINS; HIV-1 TAT PROTEIN; CELLS IN-VITRO;
   RETINITIS-PIGMENTOSA; RECOMBINANT ADENOVIRUS; MEDIATED DELIVERY;
   TEGUMENT PROTEIN; BASIC DOMAIN
AB Adenovirus (Ad)-mediated gene transfer is a promising technology for therapy of a wide variety of genetic disorders of the retina. The tropism of Ad vectors limits their utility to cells that express the coxsackie-adenovirus receptor. Upon ocular delivery, Ad vectors primarily infect the retinal pigment epithelium (RPE) and the Muller cells of the retina. However, the most frequent blinding diseases such as retinitis pigmentosa and age-related macular degeneration are associated with the expression of mutant proteins in the photoreceptors. In this study we demonstrate that adenovirus-delivered heterologous proteins fused to the herpes simplex virus tegument protein VP22 can translocate from infected cells to uninfected cells in culture and in vivo. We tested three different ocular cell lines, specifically Y79, RPE-J, and Chang C. We show that there is a 3.25-fold increase in the number of Y79 cells that take up GFP mediated by the intercellular trafficking properties of VP22. Our data are based on FACS analysis of living cells and there was no need for cell fixation for the effect to be observed. When adenovirus expressing a VP22-GFP fusion was injected into the subretinal space of adult mice, the VP22-GFP fusion peptides translocated from the RPE to all of the other layers of the retina, including the outer nuclear layer, which contains the photoreceptor cell bodies. Our study has significant implications for a wide variety of diseases of the retina and other organ systems.
C1 Univ Utah, Eccles Inst Human Genet, Dept Ophthalmol, Salt Lake City, UT 84112 USA.
   Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
C3 Utah System of Higher Education; University of Utah; Utah System of
   Higher Education; University of Utah
RP Kumar-Singh, R (通讯作者)，Univ Utah, Eccles Inst Human Genet, Dept Ophthalmol, 15N 2030E,Room 3240B, Salt Lake City, UT 84112 USA.
EM rkumar@hmbg.utah.edu
OI Kumar-Singh, Rajendra/0000-0002-7754-0713
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NR 64
TC 55
Z9 57
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD DEC
PY 2002
VL 6
IS 6
BP 813
EP 823
DI 10.1006/mthe.2002.0806
PG 11
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 628ZN
UT WOS:000180026100015
PM 12498777
OA hybrid, Green Submitted
DA 2022-11-30
ER

PT J
AU Chua, J
   Zhang, ZT
   Wong, DM
   Tan, BY
   Kulantayan, B
   Sng, CCA
   Hilal, S
   Venketasubramanian, N
   Tan, BY
   Cheung, CY
   Garhoefer, G
   Popa-Cherecheanu, A
   Wong, TY
   Chen, CLH
   Schmetterer, L
AF Chua, Jacqueline
   Zhang, Zheting
   Wong, Damon
   Tan, Bingyao
   Kulantayan, Bhavani
   Sng, Chelvin C. A.
   Hilal, Saima
   Venketasubramanian, Narayanaswamy
   Tan, Boon Yeow
   Cheung, Carol Y.
   Garhoefer, Gerhard
   Popa-Cherecheanu, Alina
   Wong, Tien Yin
   Chen, Christopher Li-Hsian
   Schmetterer, Leopold
TI Age-Related Eye Diseases in Individuals With Mild Cognitive Impairment
   and Alzheimer's Disease
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Article
DE age-related macular degeneration; diabetic retinopathy; cognitive
   impairment no dementia; Alzheimer's disease; dementia
ID QUALITY-OF-LIFE; MACULAR DEGENERATION; DIABETIC-RETINOPATHY; VISUAL
   IMPAIRMENT; GLOBAL PREVALENCE; DEMENTIA; RISK; GUIDELINES; BURDEN
AB IntroductionAlzheimer's disease (AD) and age-related eye diseases pose an increasing burden as the world's population ages. However, there is limited understanding on the association of AD/cognitive impairment, no dementia (CIND) with age-related eye diseases. MethodsIn this cross-sectional, memory clinic-based study of multiethnic Asians aged 50 and above, participants were diagnosed as AD (n = 216), cognitive impairment, no dementia (CIND) (n = 252), and no cognitive impairment (NCI) (n = 124) according to internationally accepted criteria. Retinal photographs were graded for the presence of age-related macular degeneration (AMD) and diabetic retinopathy (DR) using standard grading systems. Multivariable-adjusted logistic regression models were used to determine the associations between neurological diagnosis and odds of having eye diseases. ResultsOver half of the adults had at least one eye disease, with AMD being the most common (60.1%; n = 356), followed by DR (8.4%; n = 50). After controlling for age, sex, race, educational level, and marital status, persons with AD were more likely to have moderate DR or worse (OR = 2.95, 95% CI = 1.15-7.60) compared with NCI. In the fully adjusted model, the neurological diagnosis was not associated with AMD (OR = 0.75, 95% CI = 0.45-1.24). ConclusionPatients with AD have an increased odds of having moderate DR or worse, which suggests that these vulnerable individuals may benefit from specific social support and screening for eye diseases.
C1 [Chua, Jacqueline; Zhang, Zheting; Wong, Damon; Tan, Bingyao; Kulantayan, Bhavani; Sng, Chelvin C. A.; Wong, Tien Yin; Schmetterer, Leopold] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Chua, Jacqueline; Wong, Tien Yin; Schmetterer, Leopold] Natl Univ Singapore, Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
   [Chua, Jacqueline; Wong, Damon; Tan, Bingyao; Schmetterer, Leopold] SERI NTU Adv Ocular Engn STANCE, Singapore, Singapore.
   [Zhang, Zheting] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.
   [Wong, Damon; Tan, Bingyao; Schmetterer, Leopold] Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore, Singapore.
   [Sng, Chelvin C. A.] Natl Univ Singapore, Dept Ophthalmol, Singapore, Singapore.
   [Hilal, Saima; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian] Natl Univ Singapore, Memory Aging & Cognit Ctr, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore, Singapore.
   [Hilal, Saima; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian] Natl Univ Singapore, Memory Aging & Cognit Ctr, Yong Loo Lin Sch Med, Dept Psychol Med, Singapore, Singapore.
   [Hilal, Saima] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
   [Hilal, Saima] Natl Univ Hlth Syst, Ctr Med Phys & Biomed Engn, Singapore, Singapore.
   [Venketasubramanian, Narayanaswamy] Raffles Hosp, Raffles Neurosci Ctr, Singapore, Singapore.
   [Tan, Boon Yeow] St Lukes Hosp, Singapore, Singapore.
   [Cheung, Carol Y.] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Peoples R China.
   [Garhoefer, Gerhard] Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria.
   [Popa-Cherecheanu, Alina] Carol Davila Univ Med & Pharm, Bucharest, Romania.
   [Popa-Cherecheanu, Alina] Emergency Univ Hosp, Dept Ophthalmol, Bucharest, Romania.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; Nanyang Technological University &
   National Institute of Education (NIE) Singapore; Nanyang Technological
   University; Nanyang Technological University & National Institute of
   Education (NIE) Singapore; Nanyang Technological University; National
   University of Singapore; National University of Singapore; National
   University of Singapore; National University of Singapore; National
   University of Singapore; Raffles Hospital; Chinese University of Hong
   Kong; Medical University of Vienna; Carol Davila University of Medicine
   & Pharmacy
RP Schmetterer, L (通讯作者)，Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.; Schmetterer, L (通讯作者)，Natl Univ Singapore, Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.; Schmetterer, L (通讯作者)，SERI NTU Adv Ocular Engn STANCE, Singapore, Singapore.; Schmetterer, L (通讯作者)，Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore, Singapore.
EM leopold.schmetterer@seri.com.sg
RI Venketasubramanian, Narayanaswamy/GPP-5948-2022; Chen,
   Christopher/E-7023-2013
OI Chen, Christopher/0000-0002-1047-9225; Schmetterer,
   Leopold/0000-0002-7189-1707; Popa-Cherecheanu, Alina/0000-0003-4189-6571
FU National Medical Research Council [CG/C010A/2017_SERI, OFIRG/0048/2017,
   OFLCG/004c/2018, TA/MOH-000249-00/2018, MOH-OFIRG20nov-0014,
   NMRC/CG2/004b/2022-SERI]; National Research Foundation Singapore
   [NRF2019-THE002-0006, NRF-CRP24-2020-0001]; A*STAR [A20H4b0141];
   Singapore Eye Research Institute and Nanyang Technological University;
   Duke-NUS Medical School [Duke-NUS-KP(Coll)/2018/0009A]; SERI-Lee
   Foundation [LF1019-1]
FX This study was supported by the National Medical Research Council
   (CG/C010A/2017_SERI, OFIRG/0048/2017, OFLCG/004c/2018,
   TA/MOH-000249-00/2018, MOH-OFIRG20nov-0014, and
   NMRC/CG2/004b/2022-SERI), National Research Foundation Singapore
   (NRF2019-THE002-0006 and NRF-CRP24-2020-0001), A*STAR (A20H4b0141), the
   Singapore Eye Research Institute and Nanyang Technological University
   [SERI-NTU Advanced Ocular Engineering (STANCE) Program], the Duke-NUS
   Medical School [Duke-NUS-KP(Coll)/2018/0009A], and the SERI-Lee
   Foundation (LF1019-1) Singapore. The sponsor or funding organization had
   no role in the design or conduct of this research.
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NR 46
TC 0
Z9 0
U1 1
U2 1
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 JUL 14
PY 2022
VL 14
AR 933853
DI 10.3389/fnagi.2022.933853
PG 12
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 3K3KV
UT WOS:000833979300001
PM 35912080
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Lim, RR
   Wieser, ME
   Ganga, RR
   Barathi, VA
   Lakshminarayanan, R
   Mohan, RR
   Hainsworth, DP
   Chaurasia, SS
AF Lim, Rayne R.
   Wieser, Margaret E.
   Ganga, Rama R.
   Barathi, Veluchamy A.
   Lakshminarayanan, Rajamani
   Mohan, Rajiv R.
   Hainsworth, Dean P.
   Chaurasia, Shyam S.
TI NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic
   Retinopathy
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Review
DE NOD-like receptors; NLRP3 inflammasome; ocular tissues; innate immune
   system; diabetic retinopathy; inflammation; retina
ID NF-KAPPA-B; NLRP3 INFLAMMASOME ACTIVATION; THIOREDOXIN-INTERACTING
   PROTEIN; PIGMENT EPITHELIAL-CELLS; OXIDATIVE STRESS; AMYLOID-BETA;
   MACULAR DEGENERATION; ALU RNA; POLY(ADP-RIBOSE) POLYMERASE; MICROGLIAL
   ACTIVATION
AB Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM). International Diabetic Federations (IDF) estimates up to 629 million people with DM by the year 2045 worldwide. Nearly 50% of DM patients will show evidence of diabetic-related eye problems. Therapeutic interventions for DR are limited and mostly involve surgical intervention at the late-stages of the disease. The lack of early-stage diagnostic tools and therapies, especially in DR, demands a better understanding of the biological processes involved in the etiology of disease progression. The recent surge in literature associated with NOD-like receptors (NLRs) has gained massive attraction due to their involvement in mediating the innate immune response and perpetuating inflammatory pathways, a central phenomenon found in the pathogenesis of ocular diseases including DR. The NLR family of receptors are expressed in different eye tissues during pathological conditions suggesting their potential roles in dry eye, ocular infection, retinal ischemia, cataract, glaucoma, age-related macular degeneration (AMD), diabetic macular edema (DME) and DR. Our group is interested in studying the critical early components involved in the immune cell infiltration and inflammatory pathways involved in the progression of DR. Recently, we reported that NLRP3 inflammasome might play a pivotal role in the pathogenesis of DR. This comprehensive review summarizes the findings of NLRs expression in the ocular tissues with special emphasis on its presence in the retinal microglia and DR pathogenesis.
C1 [Lim, Rayne R.; Wieser, Margaret E.; Mohan, Rajiv R.; Chaurasia, Shyam S.] Univ Missouri, Ocular Immunol & Angiogenesis Lab, Columbia, MO 65201 USA.
   [Lim, Rayne R.; Mohan, Rajiv R.; Chaurasia, Shyam S.] Univ Missouri, Dept Biomed Sci, Columbia, MO 65201 USA.
   [Lim, Rayne R.; Mohan, Rajiv R.; Chaurasia, Shyam S.] Harry S Truman Mem Vet Hosp, Ophthalmol, Columbia, MO 65201 USA.
   [Ganga, Rama R.] Univ Missouri, Surg, Columbia, MO 65201 USA.
   [Barathi, Veluchamy A.; Lakshminarayanan, Rajamani] Singapore Eye Res Inst, Singapore 169856, Singapore.
   [Mohan, Rajiv R.; Hainsworth, Dean P.] Univ Missouri, Sch Med, Mason Eye Inst, Columbia, MO 65201 USA.
C3 University of Missouri System; University of Missouri Columbia;
   University of Missouri System; University of Missouri Columbia; US
   Department of Veterans Affairs; Veterans Health Administration (VHA);
   Harry S. Truman Memorial Veterans' Hospital; University of Missouri
   System; University of Missouri Columbia; National University of
   Singapore; Singapore National Eye Center; University of Missouri System;
   University of Missouri Columbia
RP Chaurasia, SS (通讯作者)，Univ Missouri, Ocular Immunol & Angiogenesis Lab, Columbia, MO 65201 USA.; Chaurasia, SS (通讯作者)，Univ Missouri, Dept Biomed Sci, Columbia, MO 65201 USA.; Chaurasia, SS (通讯作者)，Harry S Truman Mem Vet Hosp, Ophthalmol, Columbia, MO 65201 USA.
EM rayne.ruiyi.lim@gmail.com; mel7zd@health.missouri.edu;
   gangar@health.missouri.edu; amutha.b.veluchamy@seri.com.sg;
   lakshminarayanan.rajamani@seri.com.sg; mohanr@missouri.edu;
   HainsworthD@health.missouri.edu; chaurasias@missouri.edu
RI Chaurasia, Shyam/AAB-4709-2019
OI Chaurasia, Shyam/0000-0001-8725-676X; Rajamani,
   Lakshminarayanan/0000-0001-8214-5315
FU National Institute of Health [R01EY029795, R01EY030774]
FX This research was funded by the National Institute of Health grant
   number R01EY029795 to SSC and RRM was funded by R01EY030774.
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NR 209
TC 22
Z9 23
U1 1
U2 9
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 2020
VL 21
IS 3
AR 899
DI 10.3390/ijms21030899
PG 24
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA KY4PQ
UT WOS:000522551603053
PM 32019187
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Hwang, S
   Kang, SW
   Kim, SJ
   Jang, JW
   Kim, KT
AF Hwang, Sungsoon
   Kang, Se Woong
   Kim, Sang Jin
   Jang, Jun Won
   Kim, Kyung Tae
TI PHOTODYNAMIC THERAPY FOR SYMPTOMATIC SUBFOVEAL RETINAL PIGMENT
   EPITHELIAL DETACHMENT IN CENTRAL SEROUS CHORIORETINOPATHY Outcomes and
   Prognostic Factors
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE retinal pigment epithelial detachment; central serous chorioretinopathy;
   photodynamic therapy
ID INDOCYANINE GREEN ANGIOGRAPHY; HALF-FLUENCE; THICKNESS; EFFICACY
AB Purpose: To report the clinical outcomes of reduced-fluence photodynamic therapy (PDT) for symptomatic subfoveal retinal pigment epithelial detachment (RPED) in central serous chorioretinopathy and identify prognostic factors affecting treatment outcome.
   Methods: This retrospective interventional study included 35 eyes of 35 patients with serous subfoveal RPED with choroidal hyperpermeability. Cases with evidence of age-related macular degeneration were excluded from the study. Reduced-fluence PDT was applied to each patient. Best-corrected visual acuity, anatomical resolution of RPED, subjective symptom improvement, and complications were analyzed.
   Results: One month after reduced-fluence PDT, 28 eyes (80.0%) manifested complete resolution of subfoveal RPED. Among the patients whose eyes manifested complete resolution, 19 (67.9%) reported subjective vision improvement. This subjective improvement was significantly associated with the presence of dysmorphopsia at baseline. Logarithm of the minimal angle of resolution visual acuity improved from 0.15 (Snellen equivalent of 20/28) to 0.09 (20/25) between baseline and 3 months after PDT (P = 0.008). Older age and increased RPED height were independent risk factors of poor resolution of RPED after PDT. The mean follow-up period after treatment was 10.4 +/- 13.6 months; recurrence of RPED did not occur in any case.
   Conclusion: Subfoveal RPED in central serous chorioretinopathy responded well to reduced-fluence PDT, especially in younger patients with less RPED. Dysmorphopsia, rather than decreased visual acuity, is a main symptomatic presentation in subfoveal RPED.
C1 [Hwang, Sungsoon; Kang, Se Woong; Kim, Sang Jin; Jang, Jun Won; Kim, Kyung Tae] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, 81 Irwon Ro, Seoul 06351, South Korea.
C3 Sungkyunkwan University (SKKU); Samsung Medical Center
RP Kang, SW (通讯作者)，Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, 81 Irwon Ro, Seoul 06351, South Korea.
EM swkang@skku.edu
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NR 34
TC 6
Z9 6
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 JUN
PY 2019
VL 39
IS 6
BP 1117
EP 1124
DI 10.1097/IAE.0000000000002108
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IQ4WW
UT WOS:000480753300024
PM 29517581
DA 2022-11-30
ER

PT J
AU Mehariya, S
   Iovine, A
   Di Sanzo, G
   Larocca, V
   Martino, M
   Leone, GP
   Casella, P
   Karatza, D
   Marino, T
   Musmarra, D
   Molino, A
AF Mehariya, Sanjeet
   Iovine, Angela
   Di Sanzo, Giuseppe
   Larocca, Vincenzo
   Martino, Maria
   Leone, Gian Paolo
   Casella, Patrizia
   Karatza, Despina
   Marino, Tiziana
   Musmarra, Dino
   Molino, Antonio
TI Supercritical Fluid Extraction of Lutein from Scenedesmus almeriensis
SO MOLECULES
LA English
DT Article
DE microalgae; lutein; carotenoids; fatty acids; food additives; dietary
   supplements; pretreatment; recovery; purity
ID LIPID EXTRACTION; CARBON-DIOXIDE; MICROALGAE; PRODUCTIVITY; CAROTENOIDS;
   BIOMASS; STRAIN; FOOD
AB Lutein has several benefits for human health, playing an important role in the prevention of age-related macular degeneration (AMD), cataracts, amelioration of the first stages of atherosclerosis, and some types of cancer. In this work, the Scenedesmus almeriensis microalga was used as a natural source for the supercritical fluid (SF) extraction of lutein. For this purpose, the optimization of the main parameters affecting the extraction, such as biomass pre-treatment, temperature, pressure, and carbon dioxide (CO2) flow rate, was performed. In the first stage, the effect of mechanical pre-treatment (diatomaceous earth (DE) and biomass mixing in the range 0.25-1 DE/biomass; grinding speed varying between 0 and 600 rpm, and pre-treatment time changing from 2.5 to 10 min), was evaluated on lutein extraction efficiency. In the second stage, the influence of SF-CO2 extraction parameters such as pressure (25-55 MPa), temperature (50 and 65 degrees C), and CO2 flow rate (7.24 and 14.48 g/min) on lutein recovery and purity was investigated. The results demonstrated that by increasing temperature, pressure, and CO2 flow rate lutein recovery and purity were improved. The maximum lutein recovery (similar to 98%) with purity of similar to 34% was achieved operating at 65 degrees C and 55 MPa with a CO2 flow rate of 14.48 g/min. Therefore, optimum conditions could be useful in food industries for lutein supplementation in food products.
C1 [Mehariya, Sanjeet; Iovine, Angela; Casella, Patrizia; Molino, Antonio] ENEA, Italian Natl Agcy New Technol Energy & Sustainabl, Dept Sustainabil CR Portici, P Enrico Fermi 1, I-80055 Portici, NA, Italy.
   [Mehariya, Sanjeet; Iovine, Angela; Karatza, Despina; Marino, Tiziana; Musmarra, Dino] Univ Campania L Vanvitelli, Real Casa Annunziata, Dept Engn, Via Roma 29, I-81031 Aversa, CE, Italy.
   [Di Sanzo, Giuseppe; Larocca, Vincenzo; Martino, Maria] ENEA, Italian Natl Agcy New Technol Energy & Sustainabl, Dept Sustainabil CR Trisaia, SS Jonica 106,Km 419 500, I-7026 Rotondella, MT, Italy.
   [Leone, Gian Paolo] ENEA, Italian Natl Agcy New Technol Energy & Sustainabl, Dept Sustainabil CR Casaccia, Via Anguillarese 301, I-00123 Rome, RM, Italy.
C3 Italian National Agency New Technical Energy & Sustainable Economics
   Development; Universita della Campania Vanvitelli; Italian National
   Agency New Technical Energy & Sustainable Economics Development; Italian
   National Agency New Technical Energy & Sustainable Economics Development
RP Molino, A (通讯作者)，ENEA, Italian Natl Agcy New Technol Energy & Sustainabl, Dept Sustainabil CR Portici, P Enrico Fermi 1, I-80055 Portici, NA, Italy.
EM smehariya@gmail.com; angela.iovine@unicampania.it;
   giuseppe.disanzo@enea.it; vincenzo.larocca@enea.it;
   maria.martino@enea.it; gianpaolo.leone@enea.it;
   patrizia.casella@enea.it; karatza@irc.cnr.it; tiziana.marino@yahoo.it;
   dino.musmarra@unicampania.it; antonio.molino@enea.it
RI Molino, Antonio/AAD-6762-2022; Casella, Patrizia/AAV-6384-2020; molino,
   antonio/N-8133-2016; Mehariya, Sanjeet/L-6309-2019
OI Molino, Antonio/0000-0002-2694-5999; Casella,
   Patrizia/0000-0001-7683-4317; molino, antonio/0000-0001-6966-9640;
   Mehariya, Sanjeet/0000-0003-1801-4702
FU Bio Based Industries Joint Undertaking under the European Union [745695]
FX This research was funded by a Bio Based Industries Joint Undertaking
   under the European Union's Horizon 2020 research and innovation program
   under grant agreement No. 745695 (VALUEMAG).
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NR 42
TC 36
Z9 36
U1 2
U2 17
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1420-3049
J9 MOLECULES
JI Molecules
PD APR 4
PY 2019
VL 24
IS 7
AR 1324
DI 10.3390/molecules24071324
PG 15
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA HU0IG
UT WOS:000464954000002
PM 30987275
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Tian, YZ
   Davis, R
   Zonca, MR
   Stern, JH
   Temple, S
   Xie, YB
AF Tian, Yangzi
   Davis, Richard
   Zonca, Michael R., Jr.
   Stern, Jeffrey H.
   Temple, Sally
   Xie, Yubing
TI Screening and optimization of potential injection vehicles for storage
   of retinal pigment epithelial stem cell before transplantation
SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
LA English
DT Article
DE age-related macular degeneration; delivery vehicle; hyaluronic acid;
   retinal pigment epithelial cells; stem cells; storage; transplantation
ID ADULT HUMAN RPE; MACULAR DEGENERATION; PROTEIN EXPRESSION; HYDROGEL
   IMPROVES; HYALURONAN; MONOLAYERS; ALGINATE; CULTURE; MATRIX;
   DIFFERENTIATION
AB Retinal pigment epithelial (RPE) cells are highly specialized neural cells that have several functions essential for vision. Progressive deterioration of RPE cells in elderly individuals can result in visual impairment and ultimately the blinding disease age-related macular degeneration. Subretinal transplantation of stem cell-derived RPE cell suspensions is being explored as a strategy to recover the damaged retina and improve vision. This approach may be improved by developing a vehicle that increases postinjection cell viability and distribution and integration of RPE cells. In this study, Food and Drug Administration-approved natural polymers, including alginate, methylcellulose, and hyaluronic acid (HA), were examined for performance as cell vehicles for adult human RPE stem cells (RPESCs). We compared the effect of RPESC storage as a cell suspension in these delivery vehicles for 1-96 hr at different temperatures on subsequent cell performance in a cell culture model. RPESC survival, attachment, distribution, proliferation, and differentiation into RPE cells were monitored by microscopy over the course of 8 weeks. Our in vitro results demonstrate that RPESC suspension in a 0.2% HA solution promotes better initial cell distribution, proliferation, cobblestone formation, and expression of RPE cell markers (microphthalmia-associated transcription factor and orthodenticle homeobox 2) after 96 hr of storage. These data suggest that HA addition to the vehicle can significantly enhance RPESC performance in vitro and is a promising strategy to pursue an improved delivery vehicle supporting in vivo RPE cell transplantation.
C1 [Tian, Yangzi; Zonca, Michael R., Jr.; Xie, Yubing] SUNY Polytech Inst, Coll Nanoscale Sci, 257 Fuller Rd, Albany, NY 12203 USA.
   [Tian, Yangzi; Zonca, Michael R., Jr.; Xie, Yubing] SUNY Polytech Inst, Coll Engn, 257 Fuller Rd, Albany, NY 12203 USA.
   [Davis, Richard; Stern, Jeffrey H.; Temple, Sally] Neural Stem Cell Inst, Dept Retina Res, Rensselaer, NY USA.
C3 SUNY Polytechnic Institute; SUNY Polytechnic Institute
RP Xie, YB (通讯作者)，SUNY Polytech Inst, Coll Nanoscale Sci, 257 Fuller Rd, Albany, NY 12203 USA.; Xie, YB (通讯作者)，SUNY Polytech Inst, Coll Engn, 257 Fuller Rd, Albany, NY 12203 USA.
EM yxie@albany.edu
FU NYSTEM [C028504]
FX NYSTEM, Grant/Award Number: C028504
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NR 53
TC 3
Z9 3
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1932-6254
EI 1932-7005
J9 J TISSUE ENG REGEN M
JI J. Tissue Eng. Regen. Med.
PD JAN
PY 2019
VL 13
IS 1
BP 76
EP 86
DI 10.1002/term.2770
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
   Biology; Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Biotechnology & Applied Microbiology; Engineering
GA HI1MY
UT WOS:000456210800007
PM 30381899
DA 2022-11-30
ER

PT J
AU Ding, Y
   Kong, SC
   Kang, S
   Chen, W
AF Ding, Ying
   Kong, Shengchun
   Kang, Shan
   Chen, Wei
TI A semiparametric imputation approach for regression with censored
   covariate with application to an AMD progression study
SO STATISTICS IN MEDICINE
LA English
DT Article
DE accelerated failure time; censored covariate; compatibility; detection
   limit; multiple imputation
ID MULTIPLE IMPUTATION; LINEAR-REGRESSION; AUXILIARY VARIABLES; MODEL;
   INFERENCE; DISEASE; EXPOSURE; SUBJECT; HEALTH
AB This research is motivated by studying the progression of age-related macular degeneration where both a covariate and the response variable are subject to censoring. We develop a general framework to handle regression with censored covariate where the response can be different types and the censoring can be random or subject to (constant) detection limits. Multiple imputation is a popular technique to handle missing data that requires compatibility between the imputation model and the substantive model to obtain valid estimates. With censored covariate, we propose a novel multiple imputation-based approach, namely, the semiparametric two-step importance sampling imputation (STISI) method, to impute the censored covariate. Specifically, STISI imputes the missing covariate from a semiparametric accelerated failure time model conditional on fully observed covariates (Step 1) with the acceptance probability derived from the substantive model (Step 2). The 2-step procedure automatically ensures compatibility and takes full advantage of the relaxed semiparametric assumption in the imputation. Extensive simulations demonstrate that the STISI method yields valid estimates in all scenarios and outperforms some existing methods that are commonly used in practice. We apply STISI on data from the Age-related Eye Disease Study, to investigate the association between the progression time of the less severe eye and that of the more severe eye. We also illustrate the method by analyzing the urine arsenic data for patients from National Health and Nutrition Examination Survey (2003-2004) where the response is binary and 1 covariate is subject to detection limit.
C1 [Ding, Ying] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA.
   [Kong, Shengchun] Gilead Sci Inc, Biometr Dept, 353 Lakeside Dr, Foster City, CA 94404 USA.
   [Kang, Shan] A9 Com Inc, Ad Technol, Palo Alto, CA USA.
   [Chen, Wei] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; Gilead Sciences; Pennsylvania Commonwealth System of
   Higher Education (PCSHE); University of Pittsburgh
RP Ding, Y (通讯作者)，130 DeSoto St, Pittsburgh, PA 15261 USA.
EM yingding@pitt.edu
RI Chen, Wei/AAX-5994-2020
OI Chen, Wei/0000-0001-7196-8703
FU National Eye Institute from National Institute of Health [EY024226];
   NATIONAL EYE INSTITUTE [R01EY024226] Funding Source: NIH RePORTER
FX National Eye Institute from National Institute of Health, Grant/Award
   Number: EY024226
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NR 46
TC 3
Z9 3
U1 0
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD OCT 15
PY 2018
VL 37
IS 23
BP 3293
EP 3308
DI 10.1002/sim.7816
PG 16
WC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Medicine, Research &
   Experimental; Statistics & Probability
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Research & Experimental
   Medicine; Mathematics
GA GT3SO
UT WOS:000444423900003
PM 29845616
DA 2022-11-30
ER

PT J
AU Neelam, K
   Goenadi, CJ
   Lun, K
   Yip, CC
   Eong, KGA
AF Neelam, Kumari
   Goenadi, Catherina J.
   Lun, Katherine
   Yip, Chee Chew
   Eong, Kah-Guan Au
TI Putative protective role of lutein and zeaxanthin in diabetic
   retinopathy
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
ID PIGMENT OPTICAL-DENSITY; GLYCATION END-PRODUCTS; MACULAR PIGMENT;
   RETINAL METABOLISM; OXIDATIVE DAMAGE; MITOCHONDRIAL BIOGENESIS; SERUM
   CONCENTRATIONS; MESO-ZEAXANTHIN; LIPID-MEMBRANES; IN-VIVO
AB Diabetic retinopathy (DR) is one of the most important microvascular complications of diabetes and remains the leading cause of blindness in the working-age individuals. The exact aetiopathogenesis of DR remains elusive despite major advances in basic science and clinical research. Oxidative damage as one of the underlying causes for DR is increasingly being recognised. In humans, three hydroxycarotenoids, lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ), accumulate at the central retina (to the exclusion of all other dietary carotenoids), where they are collectively known as macular pigment. These hydroxycarotenoids by nature of their biochemical structure and function help neutralise reactive oxygen species, and thereby, prevent oxidative damage to the retina (biological antioxidants). Apart from their key antioxidant function, evidence is emerging that these carotenoids may also exhibit neuroprotective and anti-inflammatory function in the retina. Since the preliminary identification of hydroxycarotenoid in the human macula by Wald in the 1940s, there has been astounding progress in our knowledge of the role of these carotenoids in promoting ocular health. While the Age-Related Eye Disease Study 2 has established a clinical benefit for L and Z supplements in patients with age-related macular degeneration, the role of these carotenoids in other retinal diseases potentially linked to oxidative damage remains unclear. In this article, we comprehensively review the literature germane to the putative protective role of two hydroxycarotenoids, L and Z, in the pathogenesis of DR.
C1 [Neelam, Kumari; Yip, Chee Chew; Eong, Kah-Guan Au] Khoo Teck Puat Hosp, Dept Ophthalmol & Visual Sci, 90 Yishun Cent, Singapore 768828, Singapore.
   [Neelam, Kumari] Singapore Eye Res Inst, Singapore, Singapore.
   [Goenadi, Catherina J.; Lun, Katherine] Natl Univ Singapore Hosp, Dept Ophthalmol, Singapore, Singapore.
   [Eong, Kah-Guan Au] Mt Elizabeth Med Ctr, Singapore Int Eye Cataract Retina Ctr, Singapore, Singapore.
   [Eong, Kah-Guan Au] Farrer Pk Med Ctr, Int Eye Cataract Retina Ctr, Singapore, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; Mount Elizabeth Medical Centre
RP Neelam, K (通讯作者)，Khoo Teck Puat Hosp, Dept Ophthalmol & Visual Sci, 90 Yishun Cent, Singapore 768828, Singapore.
EM kumari.neelam@alexandrahealth.com.sg
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NR 93
TC 38
Z9 41
U1 3
U2 36
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 MAY
PY 2017
VL 101
IS 5
BP 551
EP 558
DI 10.1136/bjophthalmol-2016-309814
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EW2MQ
UT WOS:000402331100003
PM 28232380
DA 2022-11-30
ER

PT J
AU Coughlin, B
   Schnabolk, G
   Joseph, K
   Raikwar, H
   Kunchithapautham, K
   Johnson, K
   Moore, K
   Wang, Y
   Rohrer, B
AF Coughlin, Beth
   Schnabolk, Gloriane
   Joseph, Kusumam
   Raikwar, Himanshu
   Kunchithapautham, Kannan
   Johnson, Krista
   Moore, Kristi
   Wang, Yi
   Rohrer, Baerbel
TI Connecting the innate and adaptive immune responses in mouse choroidal
   neovascularization via the anaphylatoxin C5a and gamma delta T-cells
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   OXIDATIVE STRESS; COMPLEMENT INHIBITION; MONOCLONAL-ANTIBODY;
   RISK-FACTORS; FACTOR-B; DRUSEN; IL-17
AB Neovascular age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). An overactive complement system is associated with AMD pathogenesis, and serum proinflammatory cytokines, including IL-17, are elevated in AMD patients. IL-17 is produced by complement C5a-receptor-expressing T-cells. In murine CNV, infiltrating gamma delta T-rather than Th17-cells produce the IL-17 measurable in lesioned eyes. Here we asked whether C5a generated locally in response to CNV recruits IL-17-producing T-cells to the eye. CNV lesions were generated using laser photocoagulation and quantified by imaging; T-lymphocytes were characterized by QRT-PCR. CNV resulted in an increase in splenic IL-17-producing gamma delta T- and Th17-cells; yet in the CNV eye, only elevated levels of gamma delta T-cells were observed. Systemic administration of anti-C5- or anti-C5a-blocking antibodies blunted the CNV-induced production of splenic Th17- and gamma delta T-cells, reduced CNV size and eliminated ocular gamma delta T-cell infiltration. In ARPE-19 cell monolayers, IL-17 triggered a pro-inflammatory state; and splenocyte proliferation was elevated in response to ocular proteins. Thus, we demonstrated that CNV lesions trigger a systemic immune response, augmenting local ocular inflammation via the infiltration of IL-17-producing gamma delta T-cells, which are presumably recruited to the eye in a C5a-dependent manner. Understanding the complexity of complement-mediated pathological mechanisms will aid in the development of an AMD treatment.
C1 [Coughlin, Beth; Joseph, Kusumam; Raikwar, Himanshu; Kunchithapautham, Kannan; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, 171 Ashley Ave, Charleston, SC 29425 USA.
   [Schnabolk, Gloriane; Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA.
   [Johnson, Krista; Moore, Kristi; Wang, Yi] Alex Pharmaceut, 352 Knotter Dr, Cheshire, CT 06410 USA.
   [Raikwar, Himanshu] Pandit Bhagwat Dayal Sharma Post Grad Inst Med Sc, Rohtak, Haryana, India.
C3 Medical University of South Carolina; US Department of Veterans Affairs;
   Veterans Health Administration (VHA); Ralph H Johnson VA Medical Center;
   Pt. B.D. Sharma Post Graduate Institute of Medical Sciences (PGIMS),
   Rohtak
RP Rohrer, B (通讯作者)，Med Univ S Carolina, Dept Ophthalmol, 171 Ashley Ave, Charleston, SC 29425 USA.; Rohrer, B (通讯作者)，Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA.
EM rohrer@musc.edu
FU National Institutes of Health (NIH) [R01EY019320, C06 RR015455];
   Department of Veterans Affairs [I01 RX000444]; Foundation Fighting
   Blindness; Alexion Therapeutics; Research to Prevent Blindness (RPB),
   Inc., New York, NY; NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR015455]
   Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE [R01EY024581,
   R01EY019320] Funding Source: NIH RePORTER; Veterans Affairs
   [I01RX000444, I01BX003050] Funding Source: NIH RePORTER
FX Supported in part by the National Institutes of Health (NIH)
   (R01EY019320), Department of Veterans Affairs (I01 RX000444), Foundation
   Fighting Blindness, an unrestricted grant to MUSC from Research to
   Prevent Blindness (RPB), Inc., New York, NY and a sponsored research
   agreement by Alexion Therapeutics to BR. Animal studies were conducted
   in a facility constructed with support from the NIH (C06 RR015455).
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NR 84
TC 38
Z9 39
U1 0
U2 8
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAR 31
PY 2016
VL 6
AR 23794
DI 10.1038/srep23794
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DI0ET
UT WOS:000373168600001
PM 27029558
OA Green Published, gold
DA 2022-11-30
ER

EF